Nephrotic glomerular diseases - Internal medicine

Question 1

Nephrotic syndrome definition (A)

Answer 1

Glomerular disorders characterized by proteinuria (> 3.5 g/day) resulting in
- Hypoalbuminemia - pitting edema
- Hypogammaglobulinemia - increased risk of infection
- Hypercoagulable state - due to loss of antithrombin III
- Hyperlipidemia and hypercholesterolemia - may result in fatty casts in urine

Question 2

Minimal change disease short note (A)

Answer 2

• Most common cause of nephrotic syndrome in children.
• Usually idiopathic; may be associated with Hodgkin lymphoma.
• Normal glomeruli on H&E stain; lipid may be seen in proximal tubule cells.
• Effacement of foot processes on electron microscopy (EM)
• No immune complex deposits; negative immunofluorescence (IF)
• Selective proteinuria (loss of albumin, but not immunoglobulin)
• Excellent response to steroids (damage is mediated by cytokines from T cells).

Question 3

Focal segmental glomerulosclerosis (FSGS) Short note (A)

Answer 3

• Usually idiopathic; may be associated with HIV, heroin use, and sickle cell disease
• Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis on H&E stain.
• Effacement of foot processes on EM
• No immune complex deposits; negative IF
• Poor response to steroids; progresses to chronic renal failure

Question 4

Membranous Nephropathy Short note (A)

Answer 4

• Usually idiopathic; may be associated with hepatitis B or C, solid tumors, SLE, or drugs (e.g., NSAIDs and penicillamine)
• Thick glomerular basement membrane on H&E
• Due to immune complex deposition (granular IF), subepithelial deposits with ‘spike and dome’ appearance on EM.
• Poor response to steroids; progresses to chronic renal failure.

Question 5

Diabetic nephropathy short note (A)

Answer 5

• High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting i n hyaline arteriolosclerosis.
• Glomerular efferent arteriole is more affected than the afferent arteriole, leading to high glomerular filtration pressure.
• Hyperfiltration injury leads to microalbuminuria.
• Eventually progresses to nephrotic syndrome:
• Characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules.
• ACE inhibitors slow progression of hyperfiltration-induced damage.

Question 6

Systemic amyloidosis short note (A)

Answer 6

• Kidney is the most commonly involved organ in systemic amyloidosis.
• Amyloid deposits in the mesangium, resulting in nephrotic syndrome.
• Characterized by apple-green birefringence under polarized light after staining with Congo red.

Question 7

Clinical features of Nephrotic disease (A++)

Answer 7

A. Edema:
* Common sites for edema formation in the early stage include: dependent areas, face, peri-orbital areas and scrotum.
* Hypoalbuminemia and primary water and salt retention by kidneys are the postulated mechanisms for edema formation.

B. Hypercoagulability:
* It is multifactorial: some of the mechanisms are loss of anti-thrombin III in the urine, increased fibrinogen production by the liver, increased platelet aggregation.
* Spontaneous peripheral arterial or venous thrombosis, renal vein thrombosis, and pulmonary embolism may occur.
* Clinical features that suggest acute renal vein thrombosis include sudden onset of flank or abdominal pain, gross hematuria, a left-sided varicocele (the left testicular vein drains into the renal vein), increased proteinuria, and an acute decline in GFR.
* Chronic renal vein thrombosis is usually asymptomatic.

C. Iron-resistant microcytic hypochromic anemia due to transferrin loss.

D. Hypocalcemia as a consequence of vitamin D deficiency due to enhanced urinary excretion of cholecalciferol-binding protein.

E. An increased susceptibility to infection from urinary loss and increased catabolism of immunoglobulin.

Question 8

Treatment of nephrotic syndrome and its complications (A)

Answer 8

A. Specific treatment of the underlying morphologic entity:
* E.g. Minimal change disease: Steroids, and cytotoxic drugs
B. Measures to control proteinuria: (A++)
- Dietary protein restriction: the potential value of dietary protein restriction for reducing proteinuria must be balanced against the risk of contributing to malnutrition.
- Angiotensin-converting enzyme (ACE) inhibitors: decrease proteinuria by decreasing glomerular filtration pressure
- Controlling hypertension: keeping blood pressure below 130/80 reduces proteinuria.

Treatment of complications of nephrotic syndrome:
- Edema: should be managed cautiously by:
* Moderate salt restriction, usually 1 to 2 g/day, and the judicious use of Loop diuretics can be given in higher doses: It is unwise to remove >1.0 kg of edema per day as more aggressive diuresis may precipitate intravascular volume depletion and prerenal azotemia.
- Thromboembolism:
* Anticoagulation is indicated for patients with deep venous thrombosis, arterial thrombosis, and pulmonary embolism. Heparin may not be effective because of urinary loss of antithrombin III.
- Hyperlipidemia: may need lipid lowering agents.
- Vitamin D deficiency: Vitamin D supplementation.