Nephrology October 2022 MRCP Part – 1

Hint

This young lady has Hypokalaemia and Hypochloraemia.

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The normal blood pressure would exclude a diagnosis of Conn’s Syndrome, Congenital Adrenal Hyperplasia (CAH), or Liddle’s Syndrome (Apparent Mineralocorticoid Excess).

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Similarly, drug ingestion associated with Hypokalaemia Liquorice / Carbenoxolone is again associated with Hypertension (and Low Urinary Chloride, less than 20 mmol/L).

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Bartter Syndrome is a rare, recessive condition associated with weakness, lethargy, and growth retardation and is found in youngsters.

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Hypokalaemic Hypochloareamic Alkalosis is seen in the condition but symptoms would be more apparent at a much younger age than this lady.

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If Gitelman’s Syndrome were offered then that would be a better option.

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Therefore the most likely diagnosis is Diuretic Abuse, as the symptoms have arisen only over the last four months and no other features are apparent on examination.

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Hint

Antidiuretic Hormone (ADH) plays a crucial role in maintaining the normal concentration of the Serum.

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Released by the Posterior Pituitary, it results in the Insertion Of Aquaporin Channels in the Collecting Duct, allowing Water Reabsorption. Antidiuretic Hormone (ADH) does not inhibit Carbonic Anhydrase, nor is it related to Constriction Of Afferent or Efferent Arterioles.

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Antidiuretic Hormone (ADH) is not associated with action on the Thick Ascending Limb Of The Loop Of Henle, or in the Distal Tubule.

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Hint

The Renal Manifestations of Systemic Lupus Erythematosus (SLE) are highly variable, ranging from Mild Asymptomatic Proteinuria and / or Haematuria to Rapidly Progressive Uraemia. The various presentations are difficult to classify into clinical syndromes and histological classes. Although Lupus Nephritis affects a third of patients early in the disease it is frequently unrecognised until Nephritic and / or Nephrotic Syndrome with Renal Failure occur.

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Histologically, a number of different types of Renal Diseases are recognised in Systemic Lupus Erythematosus (SLE) with Immune-Complex Mediated Glomerular Disease being the most common. The up to date International Society of Nephrology / Renal Pathology Society 2003 classification divides these into six different patterns:

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• I – Minimal Mesangial.

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• II – Mesangial Proliferative.

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• III – Focal.

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• IV – Diffuse.

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• V – Membranous.

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• VI – Advanced Sclerosis.

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Glomeruli appear normal by Light Microscopy in Minimal Mesangial Lupus Nephritis, but Immunofluorescence demonstrates Mesangial Immune Deposits.

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Mesangial Proliferative Nephritis presents clinically as Microscopic Haematuria and / or Proteinuria. Hypertension is uncommon and Nephrotic Syndrome and Renal Impairment are very rarely seen. Biopsy demonstrates Segmental Areas Of Increased Mesangial Matrix and Cellularity, with Mesangial Immune Deposits. A few Isolated Subepithelial or Subendothelial Deposits may be visible by Immunofluorescence. The prognosis is good and specific treatment is only indicated if the disease progresses.

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Focal Disease is more advanced, but still affects less than 50% of Glomeruli. Haematuria and Proteinuria are almost always seen, and Nephrotic Syndrome, Hypertension and Elevated Serum Creatinine may be present. Biopsy demonstrates Active or Inactive Focal, Segmental or Global Endocapillary Glomerulonephritis or Extracapillary Glomerulonephritis involving less than 50% of Glomeruli, typically with Focal Subendothelial Immune Deposits, with or without Mesangial Alterations. It is further subdivided:

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• A: Active Lesions: Focal Proliferative Lupus Nephritis

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• A/C: Active And Chronic Lesions: Focal Proliferative And Sclerosing Lupus Nephritis.

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• C: Chronic Inactive Lesions With Glomerular Scars: Focal Sclerosing Lupus Nephritis.

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Prognosis is variable.

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Diffuse Glomerulonephritis is the most common and severe form of Lupus Nephritis. Haematuria and Proteinuria are almost always present, and Nephrotic Syndrome, Hypertension and Renal Impairment are common. Biopsies demonstrate Active or Inactive Diffuse, Segmental or Endocapillary Glomerulonephritis or Extracapillary Glomerulonephritis involving less than 50% of Glomeruli, typically with Diffuse Subendothelial Immune Deposits, with or without Mesangial Alterations. This class is divided into Diffuse Segmental (IV-S) when more than 50% of the Involved Glomeruli have Segmental Lesions, and Diffuse Global (IV-G) when more than 50% of Involved Glomeruli have Global Lesions. Segmental is defined as a Glomerular Lesions that involves less than half of the Glomerular Tuft.

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• IV-S (A): Active Lesions, Diffuse Segmental Proliferative Lupus Nephritis.

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• IV-G (A): Active Lesions, Diffuse Global Proliferative.

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• IV-S (A/C): Active And Chronic Lesions, Diffuse Segmental Proliferative and Sclerosing Lupus Nephritis.

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• IV-S (C): Chronic Inactive Lesions With Scars, Diffuse Segmental Sclerosing Lupus Nephritis.

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• IV-G (C): Chronic Inactive Lesions With Scars: Diffuse Global Sclerosing Lupus Nephritis.

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Immunosuppressive Therapy is required in these cases to prevent Progressive to End-Stage Renal Failure (ESRF).

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Patients with Membranous Lupus Nephritis tend to present with Nephrotic Syndrome. Microscopic Haematuria and Hypertension may also be seen. Biopsies show Global or Segmental Subepithelial Immune Deposits or Their Morphologic Sequelae, With or Without Mesangial Alterations. It may occur in combination with Class III or IV, in which case both are diagnosed. Progression is variable, and Immunosuppression is not always needed.

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In Advanced Sclerosis, more than 90% of Glomeruli are Globally Sclerosed without Residual Activity.

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Features associated with a poorer prognosis, and increased risk of progression to End-Stage Renal Failure (ESRF) include:

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• Young Age (<23)

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• Increased Serum Creatinine

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• Diffuse Proliferative Lesions (WHO Classification: Class IV), and

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• A High Chronicity Index On Renal Histological Analysis.

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With regard to the management of Lupus Nephritis, a biopsy is indicated in those patients with Abnormal Urinalysis and / or Reduced Renal Function. This can provide a Histological Classification as well as information regarding Activity, Chronicity and Prognosis. Cyclophosphamide, Mycophenolate Mofetil and Azathioprine reduce mortality in proliferative forms of Lupus Glomerulonephritis.

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Hint

Epoetin (Recombinant Human Erythropoietin) is used:

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• In Chronic Renal Failure

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• To Shorten The Period Of Anaemia In Those Receiving Platinum-Based Chemotherapy, and

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• Prevention Of Anaemia In Premature Babies With Low Birth Weight.

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Its efficacy may be impaired in certain circumstances particularly with Iron Deficiency but also with Aluminium Toxicity, Folate Deficiency and Infection. In the latter, the switch to the Acute Phase Proteins impairs its function.

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Its efficacy is unimpaired in Hyperkalaemia.

Hint

This question tests knowledge of the classification of Chronic Kidney Disease (CKD).

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The table below lists Stages Of Chronic Kidney Disease (CKD) and Corresponding Glomerular Filtration Rates (GFRs).

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The incorrect options listed above are not reflective of Stage IV Chronic Kidney Disease (CKD).

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The Suffix (p) is used to denote the presence of Proteinuria when Staging Chronic Kidney Disease (CKD). These patients have a worse prognosis, which usually warrants secondary care follow-up.

Hint

Ciclosporin causes Hypertrichosis rather than Alopecia and the most frequent adverse side effect of this drug is Nephrotoxicity.

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Post Renal Transplant, the two most common causes of declining renal function are Graft Rejection and Ciclosporin Toxicity.

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Hepatotoxicity and Paraesthesia are less common side effects of the drug. Hypertension can also be seen.

Hint

Repeated Cycles of Corticosteroid Responsive Nephrotic Syndrome suggest that this individual has Minimal Change Disease. Therefore he is likely once again to respond to High Dose Prednisolone, with a tapering dose after the first six weeks of therapy.

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In patients who fail to respond initially to Corticosteroids, Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus and Ciclosporin are Optional Second Line Agents. There are no strict indications for these, but tend to be used if there is Steroid Resistance or Steroid Dependence, Partial Response To Steroids, Frequent Relapses, and Toxicity or Contraindications to Steroids. These agents can be used sequentially if there is a failure to respond.

Hint

Henoch-Schönlein Purpura (HSP) is a Self-Limiting Vasculitis which occurs in children and young adults.

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It is characterised by:

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• Non-Thrombocytopenic Purpura

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• Arthralgia

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• Abdominal Pain, and

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• Glomerular Nephritis

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It is likely to be an Immune Complex Disease – involving IgA, but no treatment has proven efficacy.

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The disease usually settles between 4 to 6 weeks without sequelae if Kidney Involvement is Mild.

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However, this condition can occasionally relapse.

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Hint

The most common cause of Macroscopic Haematuria in a child is IgA Nephritis.

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This usually develops one to two days after a sore throat. It is most common in the second and third decades of life and is three times more common in males.

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The urine may be frankly bloody or may be the colour of cola. There are no clots in the urine and the haematuria is generally painless although some patients complain of mild loin pain.

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It tends to settle spontaneously within five days although the episodes may be recurrent lasting for one to two years.

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Renal Biopsy will show Mesangial IgA Deposition on Immunofluorescence and Light Microscopy will show Mesangial Hyper-cellularity and Matrix Expansion.

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Hint

The findings in this case point to Focal Segmental Glomerulosclerosis (FSGS), which leads to Chronic Renal Failure in half of cases.

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FSGS accounts for approximately 20% of cases of Nephrotic Syndrome in children and 40% in adults.

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• It is one of the most common Primary Glomerular Disorders causing End-Stage Renal Failure (ESRF).

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The cardinal feature on Renal Biopsy is Progressive Glomerular Scarring.

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• Early in the disease course, Glomerulosclerosis involves a minority of glomeruli (focal) and only a portion of the glomerular globe (segmental).

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• As the disease progresses more widespread Glomerulosclerosis develops. This is due to Podocyte Injury which leads to effacement of the Podocyte Foot Processes.

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80% of causes of Focal Segmental Glomerulosclerosis (FSGS) are Idiopathic, thought to be mediated by Circulating Permeability Factors. Secondary forms can be familial (due to mutations in Specific Podocyte Genes), Viral (HIV-1, Parovirus B19, CMV, EBV), Drug-Induced (Heroin, IFN, Lithium, Pamidronate, Anabolic Steroids, Calcineurin Inhibitors), or Adaptive (Unilateral Renal Agenesis, Hypertension, Sickle Cell Anaemia, Vaso-Occlusion).

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Treatment is aimed at Preserving Renal Function, and Inducing Remission of Proteinuria. Secondary causes should be excluded, as treatment should be targeted at the underlying condition in these cases.

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Idiopathic cases are treated with Renin-Angiotensin Blockade and Dietary Sodium Restriction initially.

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If Nephrotic Syndrome is present, High-Dose Glucocorticoid Therapy should be initiated and slowly tapered over a period of 3 – 6 months if a response is seen. If Focal Segmental Glomerulosclerosis (FSGS) is Glucocorticoid Resistant, therapy is with a Calcineurin Inhibitor.

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A significant number of patients with Focal Segmental Glomerulosclerosis (FSGS) go on to End-Stage Renal Failure (ESRF). Unfortunately, Focal Segmental Glomerulosclerosis (FSGS) recurs in 40% of Renal Transplants. Risk Factors For Recurrence Include: Age: 6 – 15 years, Caucasian, Rapid Course To End-Stage Renal Failure (ESRF) (<3 years), Heavy Proteinuria Prior To Transplantation and Previous Allograft Loss. Plasmapheresis has been showed to lead to remission, if used early in the course of recurrence.

Hint

The correct answer is IgA Nephritis, in this case presenting with Nephrotic Syndrome. IgA Nephritis is most common during the second and third decade of life. It commonly occurs within two days of an onset of an Upper Respiratory Tract Infection (URTI), or less commonly, infection of other Mucous Membranes (e.g. Gastrointestinal, Bladder, Breast). It should be diagnosed by a Renal Biopsy, where IgA is seen deposited in the Mesangium.

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The treatment of IgA Nephritis is variable. In a patient with Haematuria only, the treatment is conservative. When there is Nephrotic Range Proteinuria (>3 gm / day – as in this case) an 8-12 week course of Prednisolone should be prescribed. If the Proteinuria is <3 gm / day an ACE Inhibitor can be used. In all patients, careful control of Blood Pressure should be achieved, by using ACE Inhibitors in the first instance, and regular follow-up of Renal Function and Urinalysis.

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30% of children will have a spontaneous remission within 10 years, but 25% will go on to develop End-Stage Renal Failure (ESRF) within 20 years.

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Idiopathic Membranous Nephropathy accounts for 2-5% of cases of Nephrotic Syndrome in children, and 20-30% of cases in adults.

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The immune mechanism that leads to the development of Membranous Nephropathy is unknown. Histologically, it is characterised by diffuse thickening of the Glomerular Basement Membrane (GBM) on Light Microscopy. On Immunofluorescence, the thickening is caused by Immune Deposits of IgG and C3, on the Subepithelial Surface of the Glomerular Basement Membrane (GBM).

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When not Idiopathic, it is associated with:

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• Autoimmune Diseases – Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, Thyroid Disease

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• Drugs – Gold, Penicillamine, Captopril

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• Malignancy – Bronchus, Breast, Stomach, Colon, Prostate

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• Infections – Hepatitis B, Syphilis, Leprosy, Filariasis, and

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• Diabetes Mellitus.

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Membranoproliferative (or Mesangiocapillary) Glomerulonephritis can be classed into Three Types (I, II, and III) depending on which complement pathway is activated. It is associated with Systemic Lupus Erythematosus (SLE), Cryoglobulinaemia with or without Hepatitis C, Chronic Infections [Subacute Bacterial Endocarditis (SBA)] or with Neoplasms. It is not associated acutely with Upper Respiratory Tract Infections (URTI).

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Minimal Change Nephropathy is the most common form of Nephrotic Syndrome in children (peak incidence 2-3 years of age). The Histological Findings on Light Microscopy are normal or small looking Glomeruli. On Electron Microscopy there is effacement of the Epithelial Cell Foot Processes over the Outer Surface of the Glomerular Basement Membrane (GBM). It tends to be steroid responsive in children, but over 60% of children will have further relapses. In adults, it is associated with Hodgkin’s Lymphoma, and other Carcinomas.

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Post-Streptococcal Glomerulonephritis, as the name implies, occurs 10-14 days after an acute infection. The typical case occurs following infection with Group A Lancefield streptococci (β-Haemolytic strep, S. pyogenes) either causing Pharyngitis or Skin Infections. It is more common in the developing world. The histology shows diffuse Proliferative Glomerulonephritis (GN), with infiltration by Neutrophil Polymorphs. The main treatment is eradication of the infection (10/7 course of Penicillin) and symptomatic relief of the Acute Nephritis. The need for dialysis is uncommon, and complete recovery of Renal Function should occur.

Hint

This girl has a Metabolic Acidosis with pH of 7.3 and low Bicarbonate, this is most likely due to sepsis.

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She is likely to have Type 2 Diabetes Mellitus (T2DM) given the Body Mass Index (BMI) with uncontrolled Hyperglycaemia but does not have Diabetic Ketoacidosis because the Urine is Negative for Ketones, so would not require Fixed Rate Insulin Infusion.

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It is important that her glycaemia is controlled to promote recovery from the sepsis. This is best achieved with Intravenous Insulin Initially.

Hint

This patient manifests a Pulmonary Renal Syndrome which is most commonly due to an Antineutrophil Cytoplasmic Antibody Test (ANCA) Positive Vasculitis and less commonly due to Goodpasture’s Syndrome (Antiglomerular Basement Membrane [GBM] Antibodies). The history of Epistaxis makes Granulomatosis with Polyangiitis the more likely diagnosis.

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Anti-Neutrophil Cytoplasmic Antibodies [ANCA] are of two types:

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1. c-Anti-Neutrophil Cytoplasmic Antibodies (cANCA)

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• Correlates with Antiproteinase 3 Antibodies (PR3)_x000D_
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  • Proteinase-3 is a Neutral Serine Proteinase present in Azurophil Granules of Human Neutrophils.

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  • Antibodies against it may be present in isolation without a c-Anti-Neutrophil Cytoplasmic Antibodies (cANCA).

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• cANCA and Specificity for the PR3 Antigen is most specific for Granulomatosis with Polyangiitis.

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• In Granulomatosis with Polyangiitis, the level of PR3 Antibody and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Titre are related to disease activity and the antibodies typically disappear when the disease is in remission.

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2. p-Anti-Neutrophil Cytoplasmic Antibodies (pANCA) and / or Antibody To Myeloperoxidase (MPO)

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• Far less specific than c-Anti-Neutrophil Cytoplasmic Antibodies (cANCA) and can be present in a range of inflammatory conditions such as Microscopic Polyangiitis (MPA), Churg-Strauss Syndrome and Goodpasture’s Syndrome.

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• Myeloperoxidase (MPO) and p-Anti-Neutrophil Cytoplasmic Antibodies (pANCA) may also be present in Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, Sjögren’s Syndrome and occasionally in Chronic Infections.

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• They are positive in 10% of patients with Granulomatosis with Polyangiitis and are the most likely antibody to be present in this case, where Proteinase-3 is not an option.

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Granulomatosis with Polyangiitis is a Multi-Organ Autoimmune Disease which can be fatal.

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The Classical Triad consists of:

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• Necrotising Granulomatous Inflammation Of The Respiratory Tract

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• Glomerulonephritis, and

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• A Small-Vessel Vasculitis.

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A prolonged history of Epistaxis or Sinusitis is commonly found in Granulomatosis with Polyangiitis, which in some patients is also associated with an Eosinophilia. The detection of Antineutrophil Cytoplasmic Antibodies directed against Proteinase-3 is highly specific, but is found in only 50% of patients with disease localised to the Respiratory Tract and 95% with generalised Granulomatosis with Polyangiitis.

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Standard Therapy is with Cyclophosphamide and Corticosteroids. TNF-Alpha Blocking Agents, Antithymocyte Globulin and Monoclonal Anti-T Cell Antibodies can be used in disease refractory to these agents.

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Systemic Inflammation and Vasculitis contribute to Accelerated Atherosclerosis in patients with Granulomatosis with Polyangiitis and there is therefore a significantly increased incidence of Stroke, Myocardial Infarction (MI) and Occlusive Artery Disease.

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Antimitochondrial Antibodies are found in Primary Biliary Cirrhosis.

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Anticentromere Antibodies are found in CREST Syndrome / Scleroderma Syndrome.

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Antinuclear (ANA) and Anticardiolipin Antibodies are found in Systemic Lupus Erythematosus (SLE) which is not a cause of Pulmonary Renal Syndrome.

Hint

High Aldosterone and Low Renin Levels indicate Primary Hyperaldosteronism which accounts for up to 10% of all Hypertensive patients. It is the most prevalent form of Secondary Hypertension.

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Potassium Level is often normal or the lower limit of normal; as such, Hypokalaemia is not a prerequisite for the diagnosis of Conn’s Syndrome.

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Normal Renal Ultrasound Scan makes Adult Polycystic Kidney (APK) an unlikely cause of High Blood Pressure.

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High Aldosterone and Low Renin Level is not seen in Familial Essential Hypertension.

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Human Immunodeficiency Virus (HIV)-associated Nephropathy causes Proteinuria.

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Non-Hodgkin’s Lymphoma is often associated with Low CD4 Count.

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Hint

The history of Periorbital Oedema, Normal Blood Pressure and Serum Creatinine, Proteinuria and Low Serum Albumin indicates towards nephrotic syndrome.

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The Lack Of Haematuria counts against Post-Streptococcal Glomerulonephritis, and IgA Nephropathy.

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Hence, the most likely diagnosis, given the age of the patient and clinical scenario, is Minimal Change Disease.

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• The condition is much more common in this age range than Membranous Nephropathy (adults more often affected).

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• The important point about Minimal change disease is that the condition responds very well to Corticosteroid Therapy i.e. in 90% or more of sufferers in childhood within two weeks, although treatment is usually continued for a period of eight weeks.

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Alport’s Syndrome is a familial Nephritis associated with Haematuria and Progressive Sensorineural Hearing Loss and is not indicated in this patient.

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Hint

Not all cases of Post-Streptococcal Glomerulonephritis (GN) require a Biopsy.

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The Characteristic Electron Microscopy findings are described in the correct option.

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C4d Staining Positive is incorrect as this refers to the detection of BK Virus by the C4d Stain.

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Podocyte Effacement is incorrect as this is diagnostic of Minimal Change Disease.

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IgA Deposition In The Mesangium is a biopsy finding in IgA Nephropathy and so is incorrect.

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The Tram Track Appearance on Light Microscopy represents Membranoproliferative Glomerulonephritis and therefore should not be selected.

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Hint

This question demonstrates knowledge of Markers Of Glomerular Filtration Rate (GFR).

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Serum Creatinine has limitations as a marker of Glomerular Filtration Rate (GFR).

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Nystatin is an Antifungal Agent and not a marker of Glomerular Filtration Rate (GFR).

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Inulin is a Valid Marker Of Renal Function and was used experimentally in the past for many years.

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Alpha Amyloid Protein and IGF-1 have No Role In Estimating Renal Function.

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In regards to Cystatin C it is now a much more Sensitive Marker Of Kidney Function as opposed to Insulin and Insulin Resistance. More recent studies have proven this and can be referenced below

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

The most plausible diagnosis for this lady presenting with headache, bilateral blurring of the optic discs, and pupil-sparing third nerve palsy on the left is D. Sagittal sinus thrombosis. This is because sagittal sinus thrombosis is a rare condition that occurs when a blood clot forms in the sagittal sinus, which is a large vein that drains blood from the brain. This can cause increased pressure in the brain, leading to symptoms such as headache, blurred vision, and cranial nerve palsies. Sagittal sinus thrombosis is more common in women, especially during pregnancy and the postpartum period, due to hormonal changes and hypercoagulability.

The other options are less likely for the following reasons:

• A. Herpes simplex virus (HSV) encephalitis: Herpes simplex virus (HSV) encephalitis is a rare but serious infection of the brain caused by the herpes simplex virus. It can cause headache, fever, confusion, seizures, and focal neurological deficits. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not focal brain inflammation.
• B. Brainstem cerebrovascular accident (CVA): A brainstem cerebrovascular accident (CVA) is a stroke that affects the brainstem, which is the part of the brain that controls vital functions such as breathing, heart rate, and blood pressure. It can cause headache, dizziness, nausea, vomiting, and cranial nerve palsies. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not brainstem ischaemia. Moreover, a brainstem cerebrovascular accident (CVA) would not spare the pupil, as the third nerve fibers that control the pupil are located in the brainstem.
• C. Meningococcal meningitis: Meningococcal meningitis is a severe infection of the meninges, which are the membranes that cover the brain and spinal cord, caused by the bacterium Neisseria meningitidis. It can cause headache, fever, neck stiffness, photophobia, and rash. It can also cause cranial nerve palsies, especially of the sixth and seventh nerves. However, it is unlikely to cause bilateral blurring of the optic discs or pupil-sparing third nerve palsy, as these are signs of increased intracranial pressure, not meningeal inflammation.
• E. Sphenoidal wing meningioma: A sphenoidal wing meningioma is a benign tumour that arises from the meninges near the sphenoid bone, which is a bone at the base of the skull. It can cause headache, visual loss, and cranial nerve palsies, especially of the third, fourth, and sixth nerves. However, it is unlikely to cause bilateral blurring of the optic discs, as this is a sign of increased intracranial pressure, not a focal mass lesion. Moreover, a sphenoidal wing meningioma would not spare the pupil, as the third nerve fibers that control the pupil are located close to the tumour site.

Hint

His chance of having Autosomal Dominant Polycystic Kidney Disorder (ADPKD) is less than 5%. This is based on Ultrasound Scan criteria developed by screening a cohort of patients at risk for Autosomal Dominant Polycystic Kidney Disorder (ADPKD). The findings that should lead to the diagnosis being made are:

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• Two Or More Unilateral Or Bilateral Cysts In Individuals Between 15 And 30 Years Of Age.

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• Two Cysts In Each Kidney In Individuals 30 To 59 Years.

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• Four Cysts In Each Kidney In Individuals 60 Years Or Older.

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These have a Specificity of 100% with respect to diagnosis of the condition. Among patients aged between 15 and 30 years, Sensitivity is 95%, and at age 20 years the False-Negative Rate is said to be 4%. By age 30 years, Sensitivity increases to close to 100%; therefore, at this age the condition can definitely be excluded.

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Screening at age younger than 15 years is not recommended. Screening is recommended because individuals may be asked to become Kidney Donors for other family members, and early and aggressive management of Hypertension in affected individuals may delay the onset of End-Stage Renal Failure (ESRF).

Hint

The acute onset of the disease is suggestive of IgA Nephropathy which characteristically occurs in young males in their 20s and 30s.

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Haematuria occurs within 12-24 hours of Pharyngitis, accompanied also by Loin Pain, Muscle Pain and Fever. Prognosis is usually good especially in children. In adults, between 25-50% may develop End-Stage Renal Failure (ESRF). No specific treatment is available.

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Classically, the patient has Streptococcal Infection one to three weeks before the onset of Acute Nephritic Syndrome (Post-Strep GN).

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There is a Long Prodromal Systemic Illness lasting months or years in Microscopic Polyangiitis which differs from Granulomatosis with Polyangiitis in its absence of Respiratory Tract Granulomatous Inflammation.

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Hint

This patient has Systemic Lupus Erythematosus [SLE] along with Lupus Nephritis as suggested by Strongly Positive Anti dsDNA antibodies & presence of proteinuria. However if urinary RBC casts were mentioned in the question then it would become even easier to identify the renal involvement.

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The Renal Manifestations of Systemic Lupus Erythematosus [SLE] are highly variable, ranging from Mild Asymptomatic Proteinuria and / or Haematuria to Rapidly Progressive Uraemia.

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The various presentations are difficult to classify into clinical syndromes and histological classes. Although Lupus Nephritis affects a third of patients early in the disease it is frequently unrecognised until Nephritic and / or Nephrotic Syndrome with Renal Failure occur.

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Histologically, a number of different types of renal disease are recognised in Systemic Lupus Erythematosus [SLE], with Immune-Complex Mediated Glomerular Disease being the most common. The up to date International Society of Nephrology / Renal Pathology Society 2003 classification divides these into six (06) different patterns:

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• Minimal Mesangial

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• Mesangial Proliferative

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• Focal

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• Diffuse

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• Membranous, and

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• Advanced Sclerosis.

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Patients with Membranous Lupus Nephritis tend to present with Nephrotic Syndrome.

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• Microscopic Haematuria and Hypertension may also be seen.

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• Biopsies show Global or Segmental Subepithelial Immune Deposits or their Morphologic Sequelae, with or without Mesangial Alterations.

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• It may occur in combination with Class III or IV, in which case both are diagnosed.

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• Progression is variable, and immunosuppression is not always needed.

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• Cyclophosphamide, Mycophenolate Mofetil and Azathioprine reduce mortality in proliferative forms of Lupus Glomerulonephritis, but the benefit is not clear in membranous forms.

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More important to this patient’s renal disease in this patient is aggressive blood pressure control. An Angiotensin-Converting Enzyme (ACE) Inhibitor would be First Line, as it has been shown to reduce Proteinuria independently of its effect on Blood Pressure.

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Warfarin is not considered an appropriate treatment as this lady has not exhibited any prothrombotic tendencies.

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Non-Steroidal Anti-Inflammatory Medication would treat her Arthralgia but would have no effect on the prognosis of the disease.

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Therefore the correct answer should be Angiotensin-Converting Enzyme (ACE) Inhibitor for Blood Pressure Control, but immunosuppression may well be required to manage her Extra-Renal Disease.

Hint

The history of Polydipsia, Polyuria and Nocturia, in this case, is typical of Diabetes Insipidus. From the information given in the stem, we can suggest this is Nephrogenic Diabetes Insipidus secondary to Doxycycline. Other drugs which can cause this include Lithium, some Antifungals and some Anti-Virals.

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Whilst increasing her Oral Fluid Intake may relieve some of her symptoms of polydipsia, discontinuing the Doxycycline is the only way to resolve both her Polydipsia and Polyuria.

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High Dose Intranasal Vasopressin may relieve her symptoms but the most appropriate treatment is discontinuation of the Tetracycline Antibiotic.

Hint

Thrombotic Thrombocytopenic Purpura (TTP) and Haemolytic-Uraemic Syndrome (HUS) have overlapping clinical features, with up to 60% of Thrombotic Thrombocytopenic Purpura (TTP) patients missing at least one component of the classical pentad and around 30% of Haemolytic Uraemic-Syndrome (HUS) patients having Neurological Symptoms and Fever.

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Acute Kidney Injury (AKI) can be present in both conditions. It is typically more severe in Haemolytic-Uraemic Syndrome (HUS). Neurological Symptoms are much less common in patients presenting with Haemolytic-Uraemic Syndrome (HUS).

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Fever, Haemolytic Anaemia, and Thrombocytopenia can be present in both conditions.

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Hint

This pregnant lady has Hypertension and Proteinuria (as defined by a Blood Pressure above 140/90 mmHg and Proteinuria above 0.3 g/day). It would not be regarded as normal to have this high Blood Pressure or Urine Protein content.

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Hypertensive Disorders during pregnancy occur in women with Pre-existing Primary or Secondary Hypertension and in women who develop New-onset Hypertension (defined as those cases occurring after 20 weeks).

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All patients who have Hypertension during pregnancy are at increased risk of Eclampsia. Although the rate of this is decreasing, Hypertension in pregnancy remains one of the leading causes of maternal death. In addition, it can lead to Stillbirth, Preterm Birth, and Small For Gestational Age Babies.

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In pregnancy, Chronic Hypertension is defined as Hypertension that is present at the booking visit or before 20 weeks of gestation, or if the woman is already taking antihypertensive medication when she conceives. It can be primary or secondary in aetiology.

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Gestational Hypertension is new Hypertension which presents after 20 weeks without Significant Proteinuria.

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Pre-eclampsia is new Hypertension presenting after 20 weeks with significant proteinuria. Severe pre-eclampsia is pre-eclampsia with Severe Hypertension (>160/110 mmHg) and / or with symptoms [Headache, Visual Disturbance (Blurring of Vision), Abdominal Pain (especially Epigastric Pain), Nausea, Vomiting, Breathlessness, and Oedema), and / or Biochemical and Haematological Impairment.

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The presence of Significant Proteinuria in Chronic Hypertension should alert the Obstetrician to suspect underlying Renal Disease, especially in a young antenatal mother. Significant Proteinuria is defined as a Urinary Protein: Creatinine Ratio greater than 30 mg/mmol or a 24-Hour Urine Collection of more than 300 mg Protein. In pregnancy, it only indicates pre-eclampsia if it develops after 20 weeks gestation.

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Management of Chronic Hypertension in pregnancy involves determining the cause (if the Obstetrician suspects it to be Secondary), Restricting Dietary Sodium, Regular Antenatal Check-Ups, and Anti-Hypertensive Treatment. Blood Pressure should be kept less than 150/100 mmHg, unless there is evidence of target-organ damage in which case the Blood Pressure should be kept less than 140/90 mmHg.

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Antenatal mothers with Chronic Hypertension are at increased risk of developing pre-eclampsia and are therefore prescribed 75 mg of Aspirin daily from 12 weeks, which is believed to reduce the risk. Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin-II Receptor Blockers are avoided due to their increased risk of Congenital Malformations. In general, treatment should be overseen by an Obstetrician if there is Primary Hypertension, and a Renal Physician or Endocrinologist if Secondary Hypertension is suspected.

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Hint

This boy almost certainly has IgA Nephropathy, given his presentation with frank haematuria occurring in such close proximity to a recent Upper Respiratory Tract Infection.

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The findings including normal Blood Pressure, normal Serum Creatinine and Haematuria without Proteinuria point towards a benign prognosis and for this reason he only requires regular monitoring rather than intervention with Immunosuppressive Agents.

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Treatment with Corticosteroids is usually reserved for those patients with Hypertension and a Rising Serum Creatinine.

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Where there is significant Hypertension and / or Proteinuria or both, then Angiotensin-Converting Enzyme (ACE) Inhibitors are the First Choice Antihypertensive Agent.

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Post-Streptococcus Glomerulonephritis usually occurs one to three weeks after initial infection.

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Hint

Important thing to see here is the age of the subject in question.

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The sensitivity of ultrasonography to detect renal cysts (in a carrier of the ADPKD trait) depends on 1. The quality of the ultrasonography machine (with outdated machines assessments may not be reliable) and 2.Age of the propositus (first degree relative to be assessed for renal cysts).

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As a rule of thumb, in individuals aged 30 years, cysts are demonstrable by ultrasound in approximately 68% and above 30 years of age in approximately 89% of carriers of the genetic trait.

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There are two types of potential misdiagnosis.

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• In very young individuals, the diagnosis may be missed because the renal parenchyma presents with a hyperdense texture only, but even at this early stage hilar and intrarenal vessels exhibit unusually strong vascular reflexes._x000D_
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  • Occasionally a CT scan permits detection of very small incipient cysts in such cases.

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Ultrasonography Diagnostic Criteria according to age:

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• In PKD 1 Families, Age-Related Diagnostic Criteria Are Used: Two Cysts In Under 30 Years Age Group.

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• At Least Two Cysts In Each Kidney In 30-59 Years Age Group. Four Cysts In Each Kidney For Over 60 Years Group.

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An Ultrasound Scan of the Renal Tract, hence, may not be appropriate at this patient’s age, given that cysts may not become apparent until the age of 20 years.

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Gross Haematuria in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) carries a poor prognosis however Microscopic Haematuria may be a complication.

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Subarachnoid Haemorrhage (SAH) may be a cause of mortality in 9% of patients with Autosomal Dominant Polycystic Kidney Disorder (ADPKD), though 8% of patients have an Asymptomatic Intracranial Aneurysm; if the diagnosis is confirmed and there is a strong history of Subarachnoid Haemorrhage (SAH) then a Magnetic Resonance Imaging (MRI) Scan would be indicated.

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Genetic Counselling is most appropriate in this context and Genetic Linkage Analysis may be utilised.

Hint

This condition is typical of Cystinuria (Nephropathic Cystinosis), an Autosomal Recessive Genetic Defect in Membrane Transport for Cystine, Lysine, Ornithine and Arginine in Epithelial Cells. The Glomerulus is unable to resorb these Amino Acids, and they are therefore excreted into the Urine. The rBAT Gene is responsible, and there are three forms distinguished by the pattern of Tubular Amino Acid Transport.

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Cystinuria usually presents with Recurrent Nephrolithiasis in the form of Cystine Stones (which are often Bilateral, Multiple, and can form Staghorns). These can present as early as the first decade. Renal Failure can occur. The stones are Radiolucent Stones, which may also be seen with Uric Acid Stones. However, they are usually opaque on a Computed Tomography Scan (Kidney-Ureter-Bladder) (CT KUB).  Cystine Deposits within the Cornea are not classically seen, neither are Functional Defects Within The Glomeruli.

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Diagnosis of Cystinuria can be made by Stone Analysis; such stones are pale yellow and analysis reveals High Cystine Levels. It can then be confirmed by an Amino Acid Chromatogram and Quantification Of Cystine Excretion.

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First-line Management is conservative, with encouragement of large volume fluid intake (particularly in the evening, with the aim to pass urine at least once overnight). Urine pH should be regularly monitored (aiming for 7.5-8), with Sodium Bicarbonate being used if necessary (Not In Hypertensive Patients Or Those With Renal Failure).

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The aim of such treatment is to reduce the Urinary Cystine Concentration to below 300 mg/L. If this fails, d-Penicillamine, Alpha-Mercaptopropionyl Glycine or Captopril can be used.

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Cystine Stones are not easily broken by Lithotripsy, and therefore Percutaneous Removal is most often used if they do develop.

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Hint

The age of this patient and his previous response to Corticosteroids is suggestive of an underlying diagnosis of Minimal Change Nephropathy. As such, a further course of Corticosteroids is the treatment of choice.

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Given the inherent but low risks associated with Renal Biopsy, it is usually only attempted when three or more episodes of oedema have occurred.

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Very few patients with Minimal Change Disease actually progress to End-Stage Renal Disease (ESRD) and only around 10% of children with the disease suffer from Hypertension.

Hint

30-40% percent of children achieve spontaneous remission and 90% achieve remission following eight weeks treatment with High Dose Steroids.

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The disease is less common in adults, but over 80% of adults also achieve remission following treatment with Oral Glucocorticoids. 

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Hint

Renal Scintigraphy with Dimercaptosuccinic Acid (DMSA) involves administration of Radioactive Isotope which is avidly taken up by the Renal Parenchyma. This permits the identification of regions of decreased uptake that may represent acute inflammation (such as Pyelonephritis) or Renal Scarring.

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The technique of Dimercaptosuccinic Acid Scan (DMSA Scan) also allows detection of Congenital Renal Disorder.

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A Small Kidney with uniform uptake of Dimercaptosuccinic Acid (DMSA) is likely to represent Congenital Hypodysplasia, whereas a Focal Area of Reduced Cortical Uptake associated with Loss Of Contours is more likely to represent an Infection-Related Scar.

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Renal DTPA Scan involves an Isotope that is exclusively filtered by the Glomeruli, and is used to give a “Perfusion Index” and evaluate excretion (Obstruction Assessment) of the kidney.

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Voiding Cystourethrography is used to determine whether there is Vesicoureteral Reflux, which might give an increased risk (but not diagnostic) of Renal Scarring.

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Ultrasonography also does not reliably detect Low-Grade Scarring.

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Hint

Cystinuria is the Commonest Inborn Error of Amino Acid Transport.

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Amino Acids excreted in Urine are Cystine, Ornithine, Arginine and Lysine (Mnemonic – COAL).

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The Renal Stones are Radio-Opaque due to the presence of Sulphur. On Plain Film, which is not used as much in the United Kingdom anymore, they are Radiolucent. On Computed Tomography, as with almost all Stones, Cystine Stones are Radio-Opaque.

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It is inherited as an Autosomal Recessive Condition.

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Management includes Alkalinisation along with High Fluid Intake (>4 Litres / Day); d-Penicillamine may also be used.

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It is Cystinosis that leads to accumulation of Cystine in the Kidney.

Hint

A ten minute period of Hyperventilation would cause a Respiratory Alkalosis leading to an Increased Secretion Of Bicarbonate and Retention Of Hydrogen Ions.

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Arginine Vasopressin (AVP) acts on the Collecting Ducts increasing permeability to water.

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The Total Solute Excretion is approximately 700 mosmol/d.

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Sodium reabsorption is mostly through Active Transport in the Loop Of Henle with only a modest reabsorption facilitated by Aldosterone.

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The Rate of Ammonium Excretion is Proportional To The Rate Of Hydrogen Ion Excretion.

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Hint

Minimal Change Disease is typically seen in children less than 6-years-old and in a minority of adults with Nephrotic Syndrome.

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There is no Glomerular Abnormality on Light Microscopy.

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Electron Microscopy shows Effacement of the Foot Processes of Podocytes (Visceral Epithelial Cells) and a Normal Basement Membrane.

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Treatment is with steroids; disease remission often occurs within two weeks although relapse may occur.

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• Fusion of Foot Processes of Podocytes is seen on Electron Microscopy, not Light Microscopy.

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• There is no Hyalinisation; this is an abnormality seen in other renal diseases, such as Amyloidosis.

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• The Glomerular Basement Membrane is Normal on Electron Microscopy, though there is an abnormality of Podocytes with Fusion of Foot Processes.

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• Tubules may show accumulation of Lipid in Lining Cells on Light Microscopy, but not Calcification.

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• 

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Hint

The question describes the clinical picture of the Haemolytic Uraemic Syndrome with a diarrhoea prodrome. Escherichia coli is the most likely responsible pathogen.

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Haemolytic Uraemic Syndrome (HUS) is a syndrome composing of the Triad of:

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• Microangiopathic Haemolytic Anaemia

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• Low Platelets, and

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• Renal Failure.

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A number of pathogens are implicated including Escherichia coli, usually the O157:H7 Subtype. This produces a Verotoxin (also known as Shiga Toxin) which binds to Endothelial Receptors, particularly in the Renal, Gastrointestinal and Central Nervous Systems (CNS) thereby causing the clinical symptoms. Thrombin and Fibrin are deposited in the Microvasculature and cause Haemolysis of Circulating Erythrocytes. Platelets are also sequestered.

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The other pathogens which can cause Haemolytic Uraemic Syndrome (HUS) are Streptococcus pneumoniae, Shigella dysenteriae (Type 1 and 3), Human Immunodeficiency Virus (HIV) and Coxsackie Virus.

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This presentation is not classical of C. difficile as we are given no risk factors for this in the question, so this option is incorrect.

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Enterococcus faecalis is a Bowel Commensal which is unlikely to cause the degree of pathology described in this case.

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There is no reason to suspect this gentleman is Methicillin Resistant Staphylococcus aureus (MRSA) positive.

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Streptococcus viridans is an Upper Respiratory Tract and Throat Bacteria. This patient’s presentation does not involve that organ system so this option is incorrect.

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Hint

The answer lies between Renal Ultrasound Scan and Genetic Linkage Analysis. 

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Diagnosis is made by Multiple Bilateral Renal Cysts and a Positive Family History.

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Genetic Linkage Studies can exclude or make the diagnosis in younger patients. The studies require blood from at least two affected family members.

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Ultrasonography:

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• In PKD 1 Families, Age-Related Diagnostic Criteria Are Used: Two Cysts In Under 30 Years Age Group.

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• At Least Two Cysts In Each Kidney In 30-59 Years Age Group. Four Cysts In Each Kidney For Over 60 Years Group.

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• Computed Tomography is more sensitive than Ultrasound Scan (USS) and may aid in diagnosis in younger patients.

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Polycystic Kidney Disease (PKD) is an Autosomal Dominant Disorder. Mutations in at least three different genes can lead to Autosomal Dominant Polycystic Disease (APKD).

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1. PKD-1 On Chromosome 16: 85% Of Cases. Polycystin 1 Is An Integral Membrane Glycoprotein Involved In Cell/Matrix Interactions.

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2. PKD-2 On Chromosome 4: 10% Of Cases. Polycystin 2 Which May Associate With Polycystin 1 Through A Common Signalling Pathway.

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3. A Third Gene Mutation Is Known But Its Exact Chromosomal Location Is Not.

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Hint

This lady has had Recurrent Urinary Tract Infections since childhood and now presents with Pyelonephritis.

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Pyelonephritis is an uncommon infection in pregnancy and requires aggressive treatment with antibiotics.

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It is associated with preterm labour in 4% and may lead to fetal distress.

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Renal Stone Disease does predispose to developing Urinary Tract Infections but is less likely than Reflux Nephropathy.

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The correct answer is Reflux Nephropathy. This lady has a long history of Urinary Tract Infections with probable underlying Reflux Scarring and this would predispose her to developing Pyelonephritis in pregnancy.

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The answer is not Autosomal Dominant Polycystic Kidney Disease (ADPKD) as symptoms do not tend to occur before the age of 40 years.

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Bladder Outlet Obstruction should not occur in pregnancy and would cause Hydronephrosis (HDN) and Worsening Renal Function.

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Normal Physiological Urinary Stasis Of Pregnancy is incorrect as this should not cause Pyelonephritis.

Hint

Hypertension, Pedal Oedema, Nephritic Urinary Sediments (Blood and Protein Positive) in a patient with Systemic Lupus Erythematosus (SLE) suggests the diagnosis of Class IV (Diffuse Proliferative Glomerulonephritis) or Class III (Focal Segmental Glomerulonephritis) Lupus Nephritis. ds-DNA Antibodies increase the risk of Lupus Nephritis.

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Mesangial Glomerulonephritis presents with Mild Proteinuria.

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Minimal Change Glomerulonephritis, or Membranous Glomerulonephritis present with Proteinuria, which may be in the Nephrotic Range.

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The Renal Manifestations of Systemic Lupus Erythematosus (SLE) are highly variable, ranging from Mild Asymptomatic Proteinuria and / or Haematuria to Rapidly Progressive Uraemia. The various presentations are difficult to classify into clinical syndromes and histological classes. Although Lupus Nephritis affects a third of patients early in the disease it is frequently unrecognised until Nephritic and / or Nephrotic Syndrome with Renal Failure occur.

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Histologically, a number of different types of renal diseases are recognised in Systemic Lupus Erythematosus (SLE), with Immune-Complex Mediated Glomerular Disease being the most common.

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The Standard Classification divides these into Five Different Patterns:

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• I – No Disease.

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• II – Mesangial.

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• III – Focal Proliferative.

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• IV – Diffuse Proliferative.

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• V – Membranous.

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Mesangial Nephritis represents the earliest and mildest form of Glomerular Involvement. It presents clinically as Microscopic Haematuria and / or Proteinuria. Hypertension is uncommon and Nephrotic Syndrome and Renal Impairment are very rarely seen. Biopsy demonstrates segmental areas of increased Mesangial Matrix and Cellularity. The prognosis is good and specific treatment is indicated only if the disease progresses.

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Focal Proliferative Disease is more advanced, but still affects less than 50% of Glomeruli. Haematuria and Proteinuria is almost always seen, and Nephrotic Syndrome, Hypertension and Elevated Serum Creatinine may be present. Electron Microscopy shows Immune Deposits in the Subendothelial Space of the Glomerular Capillary Wall and the Mesangium. Prognosis is variable.

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Diffuse Proliferative Glomerulonephritis is the most common and severe form of Lupus Nephritis. Haematuria and Proteinuria are almost always present, and Nephrotic Syndrome, Hypertension and Renal Impairment are common. Biopsies demonstrate profuse deposits of IgG within the Glomeruli. Immunosuppressive Therapy is required in these cases to prevent progression to End-Stage Renal Failure (ESRF).

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Patients with Membranous Lupus Nephritis tend to present with Nephrotic Syndrome. Microscopic Haematuria and Hypertension may also be seen. Biopsies show diffuse thickening of the Glomerular Capillary Wall. Progression is variable, and immunosuppression is not always needed.

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With regard to the management of Lupus Nephritis, a biopsy is indicated in those patients with Abnormal Urinalysis and / or Reduced Renal Function. This can provide a histological classification as well as information regarding activity, chronicity and prognosis.

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Cyclophosphamide, Mycophenolate Mofetil and Azathioprine reduce mortality in proliferative forms of Lupus Glomerulonephritis.

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Hint

The diagnosis is Alport’s Syndrome, which is a disorder of Type 4 Collagen assembly and is inherited as an X-Linked disorder in 85% of cases.

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Fibrillin Gene abnormalities are associated with Marfan’s Syndrome.

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Type 1 Collagen disorders are associated with Osteogenesis Imperfecta; it is the main type of collagen in tendon and bone.

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Type 3 Collagen is the main component of Reticular Fibres.

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Hint

The fact that his father and brother are both affected is suggestive of an Autosomal Dominant Inherited Disorder, probably Autosomal Dominant Polycystic Kidney Disorder (ADPKD).

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Given that his father had a stroke at a young age, this raises the possibility of a Berry Aneurysm and subsequent Subarachnoid Haemorrhage (SAH).

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Autosomal Dominant Polycystic Kidney Disorder (ADPKD) affects as many as 1 in 1000 individuals and is responsible for around 10% of the United Kingdom Dialysis Burden.

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Polycystic Liver Disease is seen in 80% of patients but is usually asymptomatic. Abdominal Ultrasound has a sensitivity approaching 100% for patients above 20 years of age.

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Hypertension should be aggressively managed, with Angiotensin-Converting Enzyme (ACE) Inhibitors the therapy of choice.

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Hint

Although this lady has features of Nephritic Syndrome and may warrant Biopsy in the future, a Renal Ultrasound Scan is the best next investigation.

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Renal Ultrasound allows one to assess Kidney Size, the presence of Hydronephrosis (HDN), Cysts or Tumours and any developmental abnormalities. Doppler Traces also allow Renal Blood Flow to be assessed.

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If a clear identifiable precipitant is identified as the cause of the Acute Kidney Injury (AKI), an Ultrasound Scan may not be appropriate.

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If a patient has Acute Urinary Retention and Serum Creatinine falls spontaneously with the insertion of a Catheter, they do not necessarily need an Ultrasound Scan.

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If a patient has had an insult such as Profound Hypotension or has Acute Kidney Injury (AKI) in the context of Sepsis with a previously Normal Serum Creatinine, an Ultrasound Scan (USS) will not add much to the diagnosis unless they fail to recover with time.

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However, the above patient warrants Ultrasound Imaging.

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• A Dimercaptosuccinic Acid (DMSA) Scan is not indicated for this patient.

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• A Plain Abdominal KUB (Kidney-Ureter-Bladder) is less frequently used compared to a Computed Tomography (Kidney-Ureter-Bladder) (CT KUB) for Stone Disease, however, this patient has Nephritis.

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• Angiography is not indicated for this patient.

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• A Renal Biopsy may be indicated in the future, but an Ultrasound Scan (USS) should be performed first.

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A Renal Ultrasound Scan should be performed in all patients with Acute Kidney Injury (AKI), unless a clear treatable cause is identified.

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Hint

Copious vomiting in this patient leads to loss of gastric contents which are predominantly acidic.

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Loss of acid secretions from the stomach renders this patient deficient of acid in her blood; hence her Acid Base Status will be reflective of Metabolic Alkalosis. One may also expect a Lower Serum Potassium and Serum Chloride which are also lost in gastric secretions.

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Primary Metabolic Acidosis, Mixed Metabolic Acidosis and Respiratory Alkalosis are incorrect because the patient is in acid deficit rather than acid excess.

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There is no Primary Respiratory Pathology in the question and so Primary Respiratory Acidosis and Primary Respiratory Alkalosis are incorrect.

Hint

This patient has Nephrotic Syndrome, which is a combination of:

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• Proteinuria (Usually > 3 gm / 24 Hrs).

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• Hypoalbuminaemia (< 35 gm / Litre).

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• Oedema

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• Hyperlipidaemia.

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This patient has 7g/day proteinuria and Hypoalbuminemia, hence, the diagnosis.

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In the young adult Histological Diagnoses are in general: Minimal Change > Mesangiocapillary > Focal Segmental Glomerulosclerosis (FSGS) > lupus > Membranous > Diabetes.

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In the usual course, ideally a Renal Biopsy would be indicated as the next step to determine the cause of the Nephrotic Syndrome, however, as this patient has only one kidney, then this would be considered a relative contraindication for such a procedure.

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The most appropriate course of action here would be to undergo a Trial of Steroid Therapy.

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A High Protein Diet / Albumin Transfusion would be of little to no benefit – and the latter would need to be Salt-Poor.

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Angiotensin-Converting Enzyme (ACE) Inhibitors reduce Proteinuria and slow deterioration in Glomerular Filtration Rate (GFR).

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In this case, given the patient’s age, he may well have Minimal Change Glomerulonephritis (GN) (commonest in children), which is normally Steroid Responsive.

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In general, Steroids are tried first and then second line agents such as Cyclosporine and Cyclophosphamide are introduced if needed.

Hint

The combination of Haemoptysis (with radiological findings consistent with Pulmonary Haemorrhage) and Red Cell Casts in the Urine (indicating Glomerular Bleeding) should lead one to consider a diagnosis of Goodpasture’s Syndrome in this case.

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Goodpasture’s Syndrome is an important, and potentially rapidly fatal, cause of Alveolar Haemorrhage and Rapidly Progressive Renal Failure. It is caused by Circulating Antiglomerular Basement Membrane Antibodies, and typically causes an Acute Glomerulonephritis. It usually presents in young men in their twenties and men and women in their sixties. Despite treatment the mortality of Goodpasture’s Syndrome is 11% and it has a high morbidity with 60% of patients becoming dependent on dialysis. Renal Impairment is caused by a Crescentic Glomerulonephritis.

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It frequently has an eruptive presentation in the young, with:

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• Cough

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• Fever

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• Haemoptysis

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• Haematuria

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• Proteinuria, and

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• Red Cell Casts.

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Pulmonary Haemorrhage and Glomerular Bleeding can result in a drop in Haemoglobin.

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The most common antibody associated with Goodpasture’s Syndrome is Antiglomerular Basement Membrane Antibodies (Anti-GBM). Antiglomerular Basement Membrane Antibodies (Anti-GBM) are directed against the Goodpasture’s Antigen, which is part of the Non-Collagenous Domain of the Alpha-3(4) Collagen Chain. However, recently it has been shown that in a significant number of patients with Goodpasture’s Syndrome Antineutrophil Cytoplasmic Antibodies (ANCA) can coexist with Antiglomerular Basement Membrane Antibodies (Anti-GBM) – in one study, 30% of patients had Positive Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Serology. In this setting, Anti-Neutrophil Cytoplasmic Antibodies (ANCA) is usually Specific for p-ANCA and is directed against Myeloperoxidase.

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In general, both antibodies can be detected at presentation. This seropositivity has been shown to have important clinical and prognostic implications, and these patients may develop Extra-Renal and Extra-Pulmonary Manifestations. In addition, they are more likely to have recurrent renal or pulmonary disease. Prognosis is debated with some studies saying it is more favourable in patients with Positive Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and others showing a worse outcome in these patients.

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Plasmapheresis and Immunosuppression (typically with Cyclophosphamide and Corticosteroid) are the treatments of choice in Goodpasture’s Syndrome. This has been shown to reduce Anti-GBM Antibodies most rapidly, which results in improved morbidity and mortality. Plasmapheresis is typically given daily or on alternate days for two to three weeks. Response is assessed by monitoring symptoms and Anti-GBM Antibody Titres. Cyclophosphamide and Prednisolone then continue, typically for six to nine months following remission.

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Alport’s Syndrome is a familial Nephritis which presents with Haematuria, Progressive Renal Failure, Ocular Abnormalities and Sensorineural Deafness. It is caused by a mutation in the Type IV Collagen Genes. Inheritance is variable, but the majority are X-Linked Dominant (85%; 15% are Autosomal Recessive). There is a high spontaneous mutation rate, which means 20% of patients have no family history.

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Hint

Chronic Hypertension in pregnancy is defined as Blood Pressure of at least 140 mmHg Systolic or 90 mmHg Diastolic before pregnancy, or for women who first present for care during pregnancy as in this case, before 20 weeks of gestation.

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Proteinuria at the Third Trimester, if not present initially, favours the diagnosis of pre-eclampsia, instead of End-Organ Damage Of Chronic Hypertension.

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Women with Chronic Hypertension have an increased chance of pre-eclampsia and therefore pre-eclampsia per se does not exclude Concurrent Chronic Hypertension. In fact, the condition of pre-eclampsia tends to develop at less than 34 weeks of gestation with Chronic Hypertension, earlier than is typical in women without Antecedent Hypertension.

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Most women with Chronic Hypertension have a decrease in Blood Pressure during pregnancy. Their Blood Pressure falls toward the end of the First Trimester. Hence, Chronic Hypertension would be considered by first documentation of High Blood Pressure before 20 weeks of gestation.

Hint

Both ACE Inhibitor and Angiotensin-Receptor Blocker are contraindicated in pregnancy.

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The use of ACE Inhibitor during the second half of the pregnancy (the fourth option) has been well known to be associated with Oligohydramnios (probably resulting from Impaired Fetal Renal Function) and Neonatal Anuria, and Fetal Death.

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Although the old teaching might allow the use of Lisinopril during the First Trimester, an Observational Retrospective Cohort Study that included women with exposure to ACE Inhibitors in the First Trimester, as reported in 2006, raised the issue that the drug is associated with increased odds for Cardiovascular Defects and Central Nervous System Defects.

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Renin-Angiotensin System Antagonists should be switched to other class of Antihypertensive Drugs (Before Conception, If Possible). Hence, options B, D & E are not appropriate.

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Blood Pressure Goal during pregnancy, in general, is less aggressive (the third answer option); a very tight blood pressure control is linked with an increased risk of Fetal Growth Restriction (FGR). Pre-pregnancy doses of antihypertensive medications are not infrequently reduced, particularly in the Second Trimester.

Hint

Alport’s Syndrome is associated with a Gene Mutation resulting in a disruption in the formation of Type IV Collagen. This is due to impaired adhesion of the Organ Of Corti which contains the Auditory Sensory Cells. This is related to the Structural Integrity of the Basement Membrane, important for the Kidney, Middle Ear and Eye Function. Sensorineural Deafness results as a consequence.

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It is not associated with Conductive Deafness.

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There is no increased association with Ear Infections such as Otitis Media, Mastoiditis and Perforated Ear Drum. Hence these answers should not be selected.

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Hint

A young man presenting with Renal Failure, Haematuria and Liver and Renal Masses raises the suspicion of Polycystic Kidney Disease (PKD).

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Associated Liver Cysts are found in around 80% of individuals with Polycystic Kidney Disease (PKD). Pancreatic Cysts are rarer, and may in some cases be associated with Recurrent Pancreatitis.

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Patients are at increased risk of Renal Stones, but the predominant increase is seen in Urate Stones (Uric Acid Stones), rather than other types.

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Up to 25% of patients may have some degree of Mitral Valve Prolapse.

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MODY 5 is associated with Hepatic and Renal Cysts and Diabetes Mellitus, but that is less likely to be the diagnosis here in the presence of a Normal Glucose.

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Polycystic Kidney Disease (PKD) carries an Autosomal Dominant Pattern Of Inheritance but may occur as a De Novo Mutation in 5%.

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Hint

The Twin Aims of treating Membranous Nephropathy are:

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• First to induce a remission of the Nephrotic Syndrome, and

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• Second to prevent the development of End-Stage Renal Failure (ESRF).

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A Meta-analysis of four randomised controlled studies comparing treatments of Membranous Nephropathy showed that regimes comprising Chlorambucil or Cyclophosphamide, either alone or along with Steroids, were more effective than symptomatic treatment or treatment with Steroids alone in inducing remission of the Nephrotic Syndrome.

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A small randomised controlled study of 20 patients with a Persistent Nephrotic Syndrome and Declining Renal Function suggested that Ciclosporin A slowed the rate of Decline Of Renal Function: this requires confirmation in a larger trial.

Hint

Autosomal Dominant APKD-1 is a relatively common disorder accounting for approximately 8% of cases of End-Stage Renal Disease (ESRD).

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The best drugs for this condition are Angiotensin-Converting Enzyme (ACE) Inhibitors (e.g. Captopril, Enalapril, or Lisinopril) or Angiotensin II Receptor Antagonist Blockers (e.g. Telmisartan, Losartan, Irbesartan, or Candesartan).

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Calcium Channel Blockers are not encouraged to be used.

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However, although widely used and recommended, there is no evidence that the Renin-Angiotensin System is affected in the disease.

Hint

Studies reveal that without treatment mortality is as high as 90% in association with Goodpasture’s Syndrome.

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However the prognosis is drastically improved with the removal of antibody through Plasmapheresis, Immunosuppression with Corticosteroids and Cyclophosphamide.

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There are some studies revealing the potential of Mycophenolate Mofetil but the evidence is rather anecdotal.

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Hint

Acute Urinary Retention would not commonly cause pain overlying a Transplanted Kidney, and as this lady self-catheterises, it would be an unlikely occurrence.

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As time between the Transplant and this episode is 7 months, Allograft Rejection cannot be the underlying cause. This is because Chronic Rejection (More Than Three Months Post Transplant) is a painless process, with difficulty to control Hypertension, Proteinuria and Slowly Rising Serum Creatinine.

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Accelerated Rejection (One To Five Days Post Transplant) can present with Fever, an Acutely Tender Swollen Graft, and Rapidly Rising Serum Creatinine. Acute Rejection (Five Days To Three Months) is Clinically Silent in the majority, but can present with a Swollen, Tender Kidney. Both of these can be discounted as it has been 7 months since the patient’s transplant.

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Renal Infarction can also be discounted. This can be a Surgical Complication of Renal Transplantation, but it presents early with a Calyceal Fistula and Urinary Leak.

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Renal Stones (Renal Calculi) could cause acute pain in the region of a Transplanted Kidney, but would be less likely in this patient than infection.

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The answer in this case is Acute Pyelonephritis.

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This patient is in the Intermediate Stage of the Post-Transplantation Immunosuppression, when the patient is most Immunocompromised (Three To Six Months Post-Transplant).

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She is at High Risk of an Acute Episode of Pyelonephritis in the Transplanted Kidney, due to the Immunosuppression, the Neuropathic Bladder and Self-Catheterisation. This would present like an Acute Rejection Episode, with a Tender Swollen Graft, Low-Grade Pyrexia, and Deteriorating Graft Function.

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This would be commonly associated with Septicaemia in this patient, and requires Parenteral Antibiotics.

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If this lady were to be managed as a Transplant Rejection, with High Dose Intravenous Steroids, the result could be catastrophic

Hint

Microalbuminuria is defined as a Urine Albumin Excretion of between 30 – 300 mg per 24 Hours.

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A concentration above 300 mg / 24 Hours signifies Albuminuria and a concentration above 3.5 gm / 24 Hours signifies Overt Proteinuria.

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Microalbuminuria is not just an indicator of early renal involvement but it also identifies Increased Cardiovascular Risk with an Approximate Twofold Cardiovascular Risk above the already increased risk in the Diabetic Population.

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A useful surrogate of the Total Albumin Excretion is the Albumin : Creatinine Ratio. The Urinary Albumin : Creatinine Ratio is measured using the First Morning Urine Sample where practicable.

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Microalbuminuria is indicated where there is an Albumin : Creatinine Ratio ≥ 2.5 mg/mmol (Men) or 3.5 mg / mmol (Women).

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Proteinuria is indicated by a Ratio of ≥ 30 mg / mmol.

Hint

The history of rapidly worsening symptoms of Asthma, accompanied by Hypertension, raised Serum Creatinine and Blood and Proteinuria are features of Churg-Strauss Syndrome.

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Churg-Strauss is a Small and Medium Sized Artery Vasculitis. p-Anti-Neutrophil Cytoplasmic Antibodies (pANCA) is positive in 70% of patients.

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High Dose Steroids with the addition of Cyclophosphamide or Azathioprine are standard therapy for the condition.

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With treatment, the one-year survival rate for Churg-Strauss is 90%; 62% at five years.

Hint

It is rather young for a 33-year-old to be Hypertensive but the presence of such a degree of Urinary Protein would suggest that the lesion is of renal; origin Polyarteritis Nodosa etc.

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The Potassium Concentration is normal and although it does not exclude Conn’s Disease, it is certainly not suggestive.

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Left Ventricular Hypertrophy (LVH) would be found with Sustained Hypertension of any aetiology, as would Arteriovenous (AV).

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The Creatinine Clearance is normal.

Hint

The Renal Manifestations of Systemic Lupus Erythematosus (SLE) are highly variable, ranging from Mild Asymptomatic Proteinuria and / or Haematuria to Rapidly Progressive Uraemia. The various presentations are difficult to classify into Clinical Syndromes and Histological Classes. Although Lupus Nephritis affects a third of patients early in the disease it is frequently unrecognised until Nephritic and / or Nephrotic Syndrome with Renal Failure occur.

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Histologically, a number of different types of renal disease are recognised in Systemic Lupus Erythematosus (SLE), with Immune-Complex Mediated Glomerular Disease being the most common. The up to date International Society of Nephrology / Renal Pathology Society 2003 Classification divides these into Six Different Patterns:

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• I – Minimal Mesangial.

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• II – Mesangial Proliferative.

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• III – Focal.

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• IV – Diffuse.

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• V – Membranous.

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• VI – Advanced Sclerosis.

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Glomeruli appear normal by Light Microscopy in Minimal Mesangial Lupus Nephritis, but Immunofluorescence demonstrates Mesangial Immune Deposits.

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Mesangial Proliferative Nephritis presents clinically as Microscopic Haematuria and / or Proteinuria. Hypertension is uncommon and Nephrotic Syndrome and Renal Impairment are very rarely seen. Biopsy demonstrates Segmental Areas of Increased Mesangial Matrix and Cellularity, with Mesangial Immune Deposits. A few Isolated Subepithelial or Subendothelial Deposits may be visible by Immunofluorescence. The prognosis is good and specific treatment is only indicated if the disease progresses.

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 Focal Disease is more advanced, but still affects less than 50% of Glomeruli. Haematuria and Proteinuria are almost always seen, and Nephrotic Syndrome, Hypertension and Elevated Creatinine may be present. Biopsy demonstrates Active or Inactive Focal, Segmental or Global Endocapillary Glomerulonephritis or Extracapillary Glomerulonephritis involving less than 50% of Glomeruli, typically with Focal Subendothelial Immune Deposits, with or without Mesangial Alterations. It is further subdivided:

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• A: Active Lesions: Focal Proliferative Lupus Nephritis.

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• A/C: Active and Chronic Lesions: Focal Proliferative and Sclerosing Lupus Nephritis.

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• C: Chronic Inactive Lesions with Glomerular Scars: Focal Sclerosing Lupus Nephritis.

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Prognosis is variable.

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Diffuse Glomerulonephritis is the most common and severe form of Lupus Nephritis. Haematuria and Proteinuria are almost always present, and Nephrotic Syndrome, Hypertension and Renal Impairment Common. Biopsies demonstrate Active or Inactive Diffuse, Segmental or Global Endocapillary Glomerulonephritis or Extracapillary Glomerulonephritis involving more than 50% of all Glomeruli, typically with Diffuse Subendothelial Immune Deposits, with or without Mesangial Alterations. This class is divided into Diffuse Segmental (IV-S) when more than 50% of the involved Glomeruli have Segmental Lesions, and Diffuse Global (IV-G) when more than 50% of involved Glomeruli have Global Lesions. Segmental is defined as a Glomerular Lesion that involves less than half of the Glomerular Tuft.

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• IV-S (A): Active Lesions, Diffuse Segmental Proliferative Lupus Nephritis.

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• IV-G (A): Active Lesions, Diffuse Global Proliferative.

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• IV-S (A/C): Active and Chronic Lesions, Diffuse Segmental Proliferative and Sclerosing Lupus Nephritis.

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• IV-S (C): Chronic Inactive Lesions with Scars, Diffuse Segmental Sclerosing Lupus Nephritis.

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• IV-G (C): Chronic Inactive Lesions with Scars: Diffuse Global Sclerosing Lupus Nephritis 

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Immunosuppressive Therapy is required in these cases to prevent Progressive to End-Stage Renal Failure (ESRF).

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Patients with Membranous Lupus Nephritis tend to present with Nephrotic Syndrome. Microscopic Haematuria and Hypertension may also be seen. Biopsies show Global or Segmental Subepithelial Immune Deposits or their Morphologic Sequelae, with or without Mesangial Alterations. It may occur in combination with Class III or IV, in which case both are diagnosed. Progression is variable, and Immunosuppression is not always needed.

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In Advanced Sclerosis, more than 90% of Glomeruli are globally sclerosed without residual activity.

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With regard to the management of Lupus Nephritis, a Biopsy is indicated in those patients with abnormal urinalysis and / or reduced renal function. This can provide a histological classification as well as information regarding activity, chronicity and prognosis. Cyclophosphamide, Mycophenolate Mofetil and Azathioprine reduce mortality in proliferative forms of Lupus Glomerulonephritis.

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IgA Nephropathy is a form of Glomerulonephritis characterised by the deposition of IgA in the Glomeruli. It is a very rare lesion in Systemic Lupus Erythematosus (SLE).

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AA Amyloidosis is a systemic disorder characterised by extracellular tissue deposition of fibrils that are composed of Amyloid A Protein (an Acute-Phase Protein produced by Hepatocytes). It occurs in the course of Chronic Inflammatory Disease, but an association with Systemic Lupus Erythematosus (SLE) is very unusual.

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Focal Segmental Glomerulonephritis is one of the most common glomerular diseases to result in End-Stage Renal Failure (ESRF). It may occur as a primary condition, or in association with a number of vasculitic disorders (rarely SLE).

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Minimal Change Nephropathy is classically a diagnosis of childhood. There is Diffuse Loss of Podocyte Foot Processes, which results in Nephrotic Syndrome but not usually the other features described above.

Hint

The history of Alcohol Excess and Macroscopic Haematuria soon after an Upper Respiratory Tract Infection (URTI) should point the candidate towards IgA Nephropathy. This is further confirmed by the Normal C3 Level.

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C4d Staining Positive is incorrect as this refers to the detection of BK Virus by the C4d Stain.

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Podocyte Effacement is incorrect as this is diagnostic of Minimal Change Disease.

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The Hump-Like Appearance In Subepithelial Space is characteristic of Post-Streptococcal Glomerulonephritis.

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The Tram Track Appearance On Light Microscopy represents Membranoproliferative Glomerulonephritis and therefore should not be selected.

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Hint

In particular, Tomato and Banana have High Potassium Content and patients should be advised to avoid such foods.

Hint

This young male patient has the typical features of acute prostatitis. He needs analgesia; urine is cultured and treatment is started with trimethoprim or ciprofloxacin.

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If not promptly treated, these patients may develop a prostatic abscess as shown by high temperature with rigors, severe perineal and rectal pain with tenesmus and, on rectal examination, an enlarged, hot, tender fluctuant prostate.

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The treatment of a prostatic abscess is periurethral resection and deroofing of the abscess cavity.

Hint

Calcium Oxalate Stones are the most frequent, followed by Calcium Phosphate. Together these make up a significant majority of stones.

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Cystine Stones are rare and associated with Tubular Defects. This answer should not be selected.

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Magnesium Ammonium Phosphate Stones are associated with Urea Splitting Organisms and are not common.

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Uric Acid Stones make up about 5 – 10% of Stones and are less common than Calcium Based Stones.

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Hint

Clarithromycin is relatively contraindicated in Kidney Transplant Recipients because of its interaction with Cyclosporine.

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Quadruple Therapy containing a Proton Pump Inhibitor (PPI), Bismuth, Metronidazole, and Tetracycline, has been shown in Meta-Analysis Of Comparative Randomised Controlled Trials to achieve a similar Eradication Rate to Clarithromycin-based Triple Therapy.

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Monotherapies and Dual Therapies (the fifth and fourth answer choices) – usually a proton pump inhibitor and one antibiotic – have always had disappointing results in eradication of Helicobacter pylori.

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The second and third answer choices are theoretically effective in Helicobacter pylori infection, but Clarithromycin interacts with Cyclosporine. Being an Enzyme Inhibitor, this Macrolide will result in an (undesirable) increase the blood level of Cyclosporine.

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Bismuth-Based Quadruple Therapy, as recommended in the Maastricht Consensus Report, is the main option for Second-Line Therapy.

Hint

Tuberculous cystitis is secondary to renal tuberculosis and not due to haematogenous or lymphogenous spread.

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Therefore, changes commence around the ureteric orifices and trigone in the form of pallor of the mucosa and submucosal oedema. Tubercles appear later.

Hint

This Acute Rejection is recognised and due to Anti-IgG Antibodies to the Human Leukocyte Antigen (HLA) Incompatible Tissues with Primary Activation Of T Cells.

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The acute response is treated with Immunosuppressants.

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Hint

The Triad of Proteinuria, Hypoalbuminaemia and Oedema typifies the Nephrotic Syndrome.

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The minimum threshold for Proteinuria which is defined as ‘Nephrotic’ is 300 mg/mmol. Hence each of the options below this level are incorrect and should not be selected.

Hint

Autosomal Dominant APKD-1 is a relatively common disorder accounting for approximately 8% of cases of End-Stage Renal Disease (ESRD).

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85% of cases are due to the defect in Polycystic Kidney Disease (PKD)-1 Locus on Chromosome 16p13.3.

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Polycystic Kidney Disease (PKD)-1 encodes a large protein, Polycystin, which seems to be involved in Cell to Cell-Matrix Interaction.

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