Nephrotic Syndrome for USMLE Step 1
Nephrotic Syndrome for USMLE Step 1
Definition
- Nephrotic Syndrome: A collection of clinical findings resulting from increased glomerular permeability, characterized by heavy proteinuria (>3.5 g/day), hypoalbuminemia (<3 g/dL), generalized edema, and hyperlipidemia.
Pathophysiology
- Increased Glomerular Permeability: Damage to the glomerular filtration barrier, including the podocytes, basement membrane, or endothelium, allows larger proteins like albumin to leak into the urine.
- Proteinuria: Excessive protein loss in the urine (>3.5 g/day) reduces plasma oncotic pressure, causing fluid to accumulate in the interstitial spaces and resulting in edema.
- Hypoalbuminemia: Persistent urinary protein loss leads to decreased serum albumin levels, further contributing to fluid shifts and edema.
- Hyperlipidemia: Hypoalbuminemia triggers increased hepatic lipoprotein synthesis, leading to elevated cholesterol and triglyceride levels.
- Edema: Sodium and water retention from activation of the renin-angiotensin-aldosterone system (RAAS) and antidiuretic hormone (ADH) worsen the edema.
Etiology
- Primary Causes:
- Minimal Change Disease (MCD): The most common cause of nephrotic syndrome in children, often idiopathic. It involves effacement of podocyte foot processes on electron microscopy. Typically responsive to corticosteroids.
- Focal Segmental Glomerulosclerosis (FSGS): Common in adults, especially African Americans, and may result from conditions like obesity or HIV. Characterized by segmental glomerular scarring.
- Membranous Nephropathy: Common in adults, characterized by immune complex deposition in the glomerular basement membrane, often secondary to infections (e.g., hepatitis B, hepatitis C), malignancies, or autoimmune diseases.
- Secondary Causes:
- Diabetic Nephropathy: The leading cause of nephrotic syndrome in adults, due to hyperglycemia-induced glomerular damage.
- Lupus Nephritis: Autoimmune damage to the glomeruli in patients with systemic lupus erythematosus (SLE).
- Amyloidosis: Deposition of amyloid proteins in the kidneys, leading to nephrotic-range proteinuria.
- Infections and Drugs: Chronic infections (e.g., hepatitis B, HIV) and nephrotoxic medications like NSAIDs can also cause secondary nephrotic syndrome.
Clinical Presentation
- Edema: Periorbital swelling, peripheral edema, ascites, and pleural effusion due to fluid retention.
- Frothy Urine: Resulting from proteinuria.
- Fatigue and Weight Gain: Caused by fluid overload and protein depletion.
- Increased Infection Risk: Loss of immunoglobulins and complement proteins in the urine makes patients susceptible to infections, particularly by encapsulated organisms like Streptococcus pneumoniae.
- Hypercoagulability: Increased risk of venous thromboembolism (VTE) due to urinary loss of anticoagulants like antithrombin III and an elevated hepatic production of clotting factors.
Diagnosis
- Urinalysis:
- Proteinuria: Nephrotic-range proteinuria (>3.5 g/day).
- Urine Microscopy: May show oval fat bodies ("Maltese crosses") due to lipiduria.
- Serum Studies:
- Hypoalbuminemia: Serum albumin <3 g/dL.
- Hyperlipidemia: Elevated cholesterol and triglyceride levels.
- Renal Function: Serum creatinine may be normal or elevated, depending on the extent of renal damage.
- Renal Biopsy:
- Indicated in adults to determine the underlying cause.
- Minimal Change Disease: Shows normal light microscopy but effacement of foot processes on electron microscopy.
- FSGS: Shows segmental glomerular sclerosis.
- Membranous Nephropathy: Shows thickened basement membranes with subepithelial immune complex deposits.
Complications
- Thromboembolism: Due to loss of antithrombin III and hypercoagulability.
- Infections: Increased risk of infections due to loss of immunoglobulins in the urine.
- Acute Kidney Injury (AKI): Hypovolemia from intravascular volume depletion can lead to prerenal AKI.
- Chronic Kidney Disease (CKD): Persistent nephrotic syndrome can lead to progressive kidney damage and CKD.
Management
- General Measures:
- Diet: Sodium restriction to control edema.
- Diuretics: Loop diuretics (e.g., furosemide) to reduce edema.
- ACE Inhibitors/ARBs: Reduce proteinuria and slow CKD progression by decreasing intraglomerular pressure.
- Specific Treatments Based on Etiology:
- Minimal Change Disease: Responds well to corticosteroids like prednisone.
- FSGS: Requires corticosteroids and, in some cases, immunosuppressive agents.
- Membranous Nephropathy: May require immunosuppressive therapy (e.g., corticosteroids, calcineurin inhibitors) in severe cases.
- Diabetic Nephropathy: Focuses on strict glycemic control and the use of ACE inhibitors/ARBs.
- Anticoagulation: Consider for patients at high risk of thromboembolism (e.g., albumin <2 g/dL).
Prognosis
- Minimal Change Disease: Excellent prognosis with most patients responding well to steroids, though relapses are common.
- FSGS and Membranous Nephropathy: These may progress to chronic kidney disease if not properly managed.
- Secondary Causes: Prognosis depends on the underlying condition (e.g., better control of diabetes can slow disease progression).
Key Points
- Nephrotic syndrome is characterized by proteinuria >3.5 g/day, hypoalbuminemia, edema, and hyperlipidemia.
- Primary causes include minimal change disease, FSGS, and membranous nephropathy, while secondary causes include diabetic nephropathy, lupus, and amyloidosis.
- Diagnosis involves urinalysis, serum studies (hypoalbuminemia, hyperlipidemia), and renal biopsy in adults.
- Management includes sodium restriction, diuretics for edema, ACE inhibitors/ARBs to reduce proteinuria, and treating the underlying cause.
- Complications include thromboembolism, infections, acute kidney injury, and progression to CKD.