Topic: Glomerulonerphritis and pyelonephritis, renal failure, nephrotic syndrome, renovascular hypertension
Question: Discuss in brief the etiology, clinical features, diagnosis and treatment of nephrotic syndrome in a 40 year old adult.
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Breif Answer
Nephrotic syndrome in adults can have various causes, most commonly primary glomerulonephritis. It results in heavy proteinuria leading to hypoalbuminemia and edema.
Etiology:
– Primary glomerular disease: Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN). MCD and FSGS are more common in adults.
– Secondary causes: Diabetes mellitus, infections (HBV, HCV, HIV), cancers (lymphoma, myeloma), SLE.
Clinical features:
– Edema: Periorbital, pedal edema and weight gain due to hypoalbuminemia and sodium retention.
– Proteinuria: >3.5g/day, detected on urine dipstick and confirmed with spot urine protein:creatinine ratio.
– Hypoalbuminemia: Usually <2.5 g/dL due to large amounts of protein loss in the urine.
– Hyperlipidemia: Due to increased hepatic synthesis of lipoproteins.
– Coagulation abnormalities: Factor deficiencies can lead to increased bleeding risk.
– Hypertension: Often accompanies nephrotic syndrome and adds to renal damage.Diagnosis:
– Urine FEME (full exam of midstream specimen): Confirm presence of nephrotic range proteinuria.
– Bloods: Albumin, cholesterol, CBC, LFTs, coagulation studies.
– Renal biopsy: Only way to determine underlying histology and guide treatment. Not always required at initial presentation but if proteinuria persists for >6-12 months despite treatment, a biopsy should be done.
Treatment:
1. Identify and treat underlying cause where possible e.g. immunosuppression for MN or steroids for MCD.
2. Symptomatic management:
– ACEi/ARBs for hypertension and proteinuria reduction. Target BP <130/80 mmHg.
– Diuretics for edema. Low salt diet also recommended.
– Statins for hypercholesterolemia. Target LDL <2.5 mmol/L.
– Anticoagulation if serum albumin <20 g/L or other risks like immobilization.
– Treat infections promptly with appropriate antibiotics.
3. For persistent nephrotic syndrome, oral steroids (Prednisolone 1 mg/kg/day) are first line. Steroid-resistant disease requires other immunosuppressants like CNIs, MMF or cyclophosphamide.
4. Renal replacement therapy may be needed if GFR <15 ml/min or life-threatening complications develop.
The prognosis depends on the underlying pathology. For primary glomerular causes in adults, nearly 50% achieve complete or partial remission with treatment. The risk of progressing to end stage kidney disease is higher in adults, so close follow up is required to monitor for loss of renal function over time.
Detailed Answer
Etiology:
Primary glomerular diseases are the most common cause of nephrotic syndrome in adults. These include:
– Minimal change disease (MCD): Accounts for up to 25% of cases in adults. Due to subtle changes in podocytes seen on electron microscopy. Usually responds well to steroids. More common in children but can occur at any age.
– Focal segmental glomerulosclerosis (FSGS): About 20-25% of adult nephrotic syndrome. Scarring of glomeruli in patches. Usually progressive leading to renal failure if uncontrolled. Steroid-resistant and may require cytotoxic drugs.
– Membranous nephropathy (MN): Up to 35% of cases. Due to subepithelial immune complex deposits. May be primary (80%) or secondary (20%) to infections, drugs or autoimmune diseases. Steroid-resistant and often relapsing-remitting course. May eventually cause renal impairment without treatment.
– Diabetic nephropathy: Leading cause of secondary nephrotic syndrome. Due to chronic high blood glucose levels and hypertension damaging the kidneys. Presence of diabetic retinopathy helps confirm diagnosis. Tight control of glucose levels and blood pressure are mainstays of treatment to slow progression.
– Other secondary causes include lupus, infections, multiple myeloma, lymphomas and medications. Extensive work up is required to rule out secondary causes before diagnosing primary glomerulonephritis.
Clinical features:
– Severe edema due to hypoalbuminemia from protein loss. Can lead to anasarca in some cases. Causes significant morbidity on its own.
– Hyperlipidemia: Due to increased hepatic synthesis of lipids. Can increase risk of atherogenesis. Statin therapy usually required.
– Hypercoagulable state: Due to loss of coagulation factors and antithrombin in the urine. Causes increased risk of venous thromboembolism like DVTs and PEs. Prophylactic anticoagulation often used especially when albumin <20 g/L.
– Hypertension: Common and exacerbated by the sodium retention. Needs to be tightly controlled, usually with ACE inhibitors or ARBs which also reduce proteinuria.
– Infections: Increased susceptibility due to edema and loss of IgM antibodies in the urine. Any signs of infection like fever or leukocytosis should be investigated and treated promptly.
– Renal impairment develops in some patients, especially with delayed diagnosis or treatment and secondary causes of nephrosis. Needs close monitoring with blood pressure control and inhibition of the renin-angiotensin system to delay progression to ESKD.
Diagnosis:
– Urine dipstick shows heavy proteinuria, >3.5 g/day. Confirmed with spot urine protein:creatinine ratio.
– Hypoalbuminemia <3.5 g/dL, due to loss of albumin in the urine.
– Hypercholesterolemia. Total cholesterol often >6.5 mmol/L due to increased hepatic synthesis.
– Full blood count may show anemia of chronic disease and elevated creatinine if renal impairment present.
– Coagulation studies: Prolonged APTT and INR, reduced fibrinogen, AT3, factors V and VIII.
– Renal biopsy: Only way to determine underlying histology and prognosis. Required if suspected secondary cause, atypical features or if proteinuria persists >6-12 months with treatment.
Treatment:
1. Primary treatment is managing complications:
– Strict sodium restriction and diuretics for edema. Often requires high doses of loop diuretics.
– ACEi/ARBs for hypertension and reducing proteinuria. Target BP <130/80 mmHg and proteinuria <3 g/day.
– Statins for hyperlipidemia. Aim for LDL <2.5 mmol/L or 50% reduction from baseline.
– Prophylactic anticoagulation when serum albumin <20 g/L. Therapeutic anticoagulation if venous thromboembolism occurs.
2. Find and treat any underlying secondary causes e.g. control DM, treat infections, stop causal medications.
3. For primary glomerulonephritis, first line is prednisolone 1 mg/kg/day for at least 4 weeks. MCD and some MN cases respond well, allowing slow taper of steroids. For steroid-resistant or dependent FSGS/MN, add immunosuppressives like cyclophosphamide, MMF, CNIs. These have significant side effects so the benefits must outweigh risks.
4. Renal biopsy may be repeated to assess response to treatment. Partial or complete remission can take 6-12 months to achieve in some cases. Treatment may need modification depending on follow up biopsy results.
5. A small number of patients progress to end stage kidney disease despite treatment and require renal replacement therapy with dialysis or transplantation. This tends to occur more often when treatment is delayed or in secondary nephrotic syndrome.
Close follow up is required for all patients with nephrotic syndrome to monitor complications, response to treatment and look for relapses. The condition can wax and wane, and may take years to completely resolve. P
