Nephrotic Syndrome
Nephrology
Illness script · Nephrology
Nephrotic Syndrome
Glomerular disease causing massive proteinuria (>3.5 g/day) with hypoalbuminemia, edema, and hyperlipidemia/lipiduria.
This illness script for Nephrotic Syndrome covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.
01
Predisposing factors
- Most common cause in children: minimal change disease (MCD)
- Most common cause in adults: focal segmental glomerulosclerosis (FSGS)
- Membranous nephropathy: #1 cause of nephrotic syndrome in white adults; associated with PLA2R antibody, HBV, SLE, malignancy
- Diabetic nephropathy: leading cause overall worldwide
- Secondary causes: HIV (→FSGS), amyloidosis, lupus, NSAIDs, gold, heroin
- Membranoproliferative GN: associated with HCV, cryoglobulinemia
02
Presentation
- Triad: pitting edema (periorbital, peripheral), frothy urine, weight gain
- Hypoalbuminemia <3 g/dL is hallmark
- Hyperlipidemia and lipiduria (Maltese cross oval fat bodies on urinalysis)
- Proteinuria >3.5 g/day (nephrotic range)
- Children with MCD: abrupt periorbital edema, often post-viral, NO hematuria
- Risk of spontaneous bacterial peritonitis, DVT/PE, renal vein thrombosis
03
Pathophysiology
- Podocyte injury/loss → disruption of glomerular filtration barrier → massive protein leak
- Hypoalbuminemia → reduced oncotic pressure → fluid shifts to interstitium → edema
- Compensatory hepatic lipoprotein synthesis + reduced lipid catabolism → hyperlipidemia/lipiduria
- Loss of antithrombin III, protein C/S → hypercoagulable state (renal vein thrombosis risk)
04
Diagnostics
- Urinalysis: 3-4+ protein, oval fat bodies, fatty casts (Maltese cross under polarized light)
- 24-hr urine protein >3.5 g/day OR urine protein:creatinine ratio >3.5
- Serum: low albumin, high cholesterol/triglycerides
- Renal biopsy: gold standard for definitive etiology in adults
- Complement levels, ANA, HBV/HCV, serum protein electrophoresis to evaluate secondary causes
05
Management
- MCD (children): first-line oral prednisone — typically dramatic remission
- MCD relapses or steroid-resistant: cyclophosphamide or cyclosporine
- Membranous nephropathy: ACE inhibitor/ARB for antiproteinuric effect; immunosuppression (rituximab, cyclophosphamide + steroids) for progressive disease
- FSGS: high-dose steroids; calcineurin inhibitors if steroid-resistant
- All nephrotic patients: salt restriction, diuretics (furosemide) for edema, statins for hyperlipidemia, anticoagulation if hypercoagulable/renal vein thrombosis
- ACE inhibitors/ARBs reduce proteinuria in all causes
06
Clinical pivots
How to separate this script from the look-alikes that show up on exams and on the wards.
Nephritic Syndrome
Nephritic = hematuria + RBC casts + HTN + oliguria + mild proteinuria (<3.5 g/day); nephrotic = massive proteinuria, no RBCs
Congestive Heart Failure
CHF edema: elevated JVP, S3, pulmonary crackles; nephrotic has low albumin, frothy urine, no cardiac signs
Hepatic Cirrhosis
Cirrhosis has ascites, jaundice, spider angiomata, elevated LFTs; urine protein is minimal without coexisting renal disease
Preeclampsia
Nephrotic-range proteinuria in pregnancy after 20 weeks + HTN = preeclampsia; no HTN or gestational context points to primary nephrotic syndrome
Keep reading
Full library- NephrolithiasisCrystalline stone formation in the urinary tract causing obstruction, colicky flank pain, and hematuria.
- Neuroleptic malignant syndromeLife-threatening hyperdopaminergic blockade reaction to antipsychotics causing hyperthermia, rigidity, autonomic instability, and altered mental status.
Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.