Nephrotic Syndrome Question and Answers

Question 1. Enumerate the common causes of Nephrotic Syndrome.
Answer. It is a clinical complex with number of renal and extrarenal features

• Hypoproteinemia
• Hypoalbuminemia
• Generalized edema or anasarca
• Hypercholesterolemia
• Hypercoagulability.

1. Primary glomerular diseases

• Minimal change nephropathy.
• Mesangioproliferative glomerulonephritis.
• Membranous nephropathy.
• Focal and segmental glomerulosclerosis.
• Crescentic glomerulonephritis

2. Idiopathic:

3. Secondary to other diseases:

• Infections: Malaria, hepatitis B, herpes zoster,
  streptococcal and staphylococcal infections, syphilis,
  leprosy, schistosomiasis.
• Drugs: NSAIDs, Heavy metals such as gold, anti convulsants, penicillamine, ACE inhibitors, heroin,rifampicin, tolbutamide and probenecid.
• Malignancy: Hodgkin’s disease and other lymphomas.
• Systemic diseases: Diabetes mellitus, amyloidosis, systemic lupus erythematosus, Henoch­Schonlein purpura, cryoglobulinemia, polyarteritis nodosa.
• Familial disorders: Congenital (neonatal) nephrotic syndrome, Alport’s syndrome, Fabry’s disease
• Miscellaneous conditions: Reflx nephropathy, renal vein thrombosis, toxemia of pregnancy, allergic reactions to insect bites, pollens and vaccines, renal artery stenosis.

Question 2.  Outline the management of Nephrotic Syndrome.
Answer. Management of nephrotic syndrome involves:

• Scientific treatment of underlying morphology or causative disease
• General measures to control nephritic complications
• Treatment to reduce proteinuria
  Non-specifi measures that may reduce proteinuria include ACE and NSAIDs.
  ACE­I and ARBs (angiotensin­receptor blockers) reduce proteinuria and slows the rate of progression of rate of renal failure by lowering intraglomerular pressure and preventing development of hemodynamically mediated focal segmental *glomerulosclerosis.
• Edema: Advice patient to take low sodium diet i.e.1 to 2 g/day. In mild edema thiazide induce gentle diuresis.
  In moderate edema frusemide in doses of 80 to 120 mg/day or torsemide 20 to 40mg/day is given.
  In patients with severe edema frusemide 20 to 40mg/day is combined with spironolactone 100 to 200mg/day for complete resorption of sodium throughout the nephron.
• Hypercholesterolemia: It is treated by the lipid lowering agent specially statins. Atorvastatin 20 mg OD or BD
  Anticoagulation is needed for patient with deep vein thrombosis, arterial thrombosis and pulmonary embolism.
• Antiplatelet agents and warfarin could be advocated.
• Diet: Restricted protein diet is advised since high protein diet accelerates progression of nephritic syndrome.
• Vitamin D supplementation is advisable.
• Antibiotics: Aggressive antibiotic therapy is given in nephrotic syndrome as chances of sepsis are always present. Mainly cephalexin are given
• Corticosteroids: Produce rapid and complete remission with clearing of proteinuria in 90% cases.
  Dose -Prednisolone 1 mg/kg/day, maximum 80 mg/ day. Remission usually occurs between days 7 and 14, though some patients need up to 16 weeks therapy to achieve complete remission.
  Prednisolone dose is reduced to 0.5 mg/kg/day and then tapered slowly.
  An attmpt to stop treatment should be made after 8 weeks.
  In patients who relapse, course of prednisolone should be repeated.
• Immunosuppressive drugs: In steroid­resistant patients, or in those in whom remission can only be maintained by heavy doses of steroids, cyclophosphamide 1.5–2 mg/kg/ day for 8–12 weeks with concomitant prednisolone 7.5–15 mg/day.
• Levamisole: In corticosteroid­dependent children 2.5 mg/ kg to maximum 150 mg on alternate days is useful in maintenance of remission.

Question 3. Describe the clinical features and diagnostic features of nephrotic syndrome.
Answer.

Clinical Features Nephrotic Syndrome

• Age and sex: Nephrotic syndrome is two to three times more common in childhood with peak incidence at 2–3 years.
  In this age group, there is a male : female ratio of 2.5 : 1,in adults, sex incidence is equal.
• Edema: It is peripheral involving the limbs, particularly lower limbs.
  In children, edema may be more obvious in the face and abdomen.
  Usually, massive generalized anasarca, the patient almost weighing double his true weight.
  Intense edema of the scrotum or vulva may occur.
  There may be bilateral hydrothorax.
  Edema may persist for many weeks or months.
  Spontaneous subsidence with diuresis (nephrotic crisis) may occur, to be followed again by increase of edema.
• Gastrointestinal symptoms: Anorexia causes severe malnutrition, Diarrhea and vomiting due to edema of intestinal wall.
• General symptoms: Prolonged protein loss causes anorexia,lethargy, tiredness, frequent infections and muscle wasting.
  Dyspnea may occur, if there is flid in the pleural cavity.
• Blood pressure: There may be periods of hypertension;ultimately with development of chronic nephritis permanent hypertension may develop.

Diagnostic Features Nephrotic Syndrome

Diagnosis is not diffilt when there is massive generalized edema with albuminuria, hypoproteinemia and hypercholesterolemia.
Diagnosis is based on clinical signs and investigations

Clinical Signs Nephrotic Syndrome

• Physical examination reveals generalized edematous person.
• Edema may persist for many weeks or months.
• Tachycardia is present while blood pressure is normal.
• Pittng edema is present over legs and feet, abdominal walls and lower eyelids.
• Eyelids become puff
• At places where edema is severe ascites and pleural effsion are seen.
• Kidneys are not palpable.

Investigations Nephrotic Syndrome

1. Urine examiation:

• Oliguria while edema is forming, dieresis or normal amount of urine during period of subsidence of edema.
• Proteinuria: It is massive, usually more than 5 g/day though variable from time to time; urine becomes almost solid on boiling. Daily loss of protein may be 20–50 g.
• 24 hour urine shows excretion of albumin or protein more than 3.5 g/day.
• Red blood cells are absent or few are seen
• Casts: Fatt casts, tubular cells, oval fat bodies, doubly refractile bodies are seen

2. Blood examination: Nephrotic Syndrome

• Anemia: It is slight normochromic.
• Hypoalbuminemia: Serum albumin usually less than 3 g/100 mL. Total serum globulin concentration frequently lowered with often elevation of α2 and β-globulins.
• Serum lipids show increase in LDL levels and cholesterol.
• ESR is raised due to hyperfirinogenemia.
• Serum complement level: Serum complement C3 and C4 levels get reduced.
• Other biochemical tests, i.e. blood urea, serum creatinine, creatinine clearance and electrolytes are normal.

3. Ultrasound of abdomen: It can show normal small or large kidneys which depends on the underlying cause.
Amyloid and diabetic kidneys are large while kidney in glomerulonephritis is small.

4. Renal biopsy: It is normal on light microscopy but electron microscopy shows typical abnormalities (effcement of epithelial cell foot processes).

Question 4. Describe briefl investigation and management of nephrotic syndrome.

Answer. Investigation of Nephrotic Syndrome

Urine examination: Nephrotic Syndrome

• Oliguria while edema is forming, dieresis or normal amount of urine during period of subsidence of edema.
• Proteinuria: It is massive, usually more than 5 g/day though variable from time to time; urine becomes almost solid on boiling. Daily loss of protein may be 20–50 g.
• 24-hour urine shows excretion of albumin or protein more than 3.5 g/day.
• Red blood cells are absent or few are seen
• Casts: Fatt casts, tubular cells, oval fat bodies, doubly refractile bodies are seen

Blood Examination: Nephrotic Syndrome

• Anemia: It is slight normochromic.
• Hypoalbuminemia: Serum albumin usually less than 3 g/100 mL. Total serum globulin concentration frequently lowered with often elevation of α2 and β-globulins.
• Serum lipids show increase in LDL levels and cholesterol.
• ESR is raised due to hyperfirinogenemia.
  Serum complement level: Serum complement C3 and C4
• levels get reduced.
  Other biochemical tests, i.e. blood urea, serum creatinine,
• creatinine clearance and electrolytes are normal.
• Ultrasound of abdomen: It can show normal small or large kidneys which depends on the underlying cause.
  Amyloid and diabetic kidneys are large while kidney in glomerulonephritis is small.
• Renal biopsy: is normal on light microscopy but electron microscopy shows typical abnormalities (effcement of epithelial cell foot processes).

Question5 . Enumerate the complications and outline the management of nephrotic syndrome.

Answer. Complications of Nephrotic Syndrome

• Protein malnutrition: Due to protein loss
• Ascites, pleural and pericardial effsion
• Accelerated atherosclerosis and coronary artery disease
• Pulmonary thromboembolism, stroke, deep vein thrombosis due to hypercoagulability
• Vitamin D defiiency is responsible for hypocalcemia
• Microcytic hyperchromic anemia
• Hypothyroidism due to depressed thyroxin level due to loss of thyroxin, binding globulin.
• Chronic renal failure eventually leading to end stage renal diseases and require hemodialysis and renal transplantation

Management of nephrotic syndrome involves:

• Scientific treatment of underlying morphology or causative disease
• General measures to control nephritic complications