Nephrotic Syndrome
Nephrotic Syndrome - Diagnosis, etiologies and complication management of nephrotic syndrome.
Practical orientation: Nephrotic syndrome is a phenotype. Always assess complications: volume overload, thrombosis risk, infection risk and dyslipidemia.
Use first: clinical summary and algorithm.
Then: differential diagnosis, workup and management tables.
Escalate: use red flags and biopsy/urgent-care sections.
Clinical summary
Definition
Heavy proteinuria with hypoalbuminemia and edema; hyperlipidemia is common but not required.
Mechanism
Podocyte or GBM injury causing high albumin leak.
Major complications
Volume overload, thrombosis, infection, hyperlipidemia, vitamin D deficiency and hypothyroidism.
Biopsy
Required in most adults unless diagnosis is clear and biopsy would not change management.
Diagnostic criteria and pathophysiology
| Feature | Explanation |
|---|---|
| Proteinuria | Usually >3.5 g/day or UPCR >3 g/g. |
| Hypoalbuminemia | Urinary losses and tubular metabolism exceed hepatic synthesis. |
| Edema | Primary sodium retention and/or low oncotic pressure with RAAS activation. |
| Hyperlipidemia | Increased LDL and triglycerides from low oncotic pressure and altered hepatic metabolism. |
Etiologies
| Group | Examples |
|---|---|
| Primary podocyte/GBM disease | MCD, FSGS, MN. |
| Other glomerular disease | IgAN, MPGN and lupus nephritis class V can present nephrotically. |
| Systemic disease | Diabetes, amyloidosis, SLE, malignancy, infections and drugs. |
Associated conditions
| Trigger/condition | Typical lesion |
|---|---|
| NSAIDs, penicillamine | MCD or MN. |
| Lithium, interferon, pamidronate, HIV | MCD or collapsing FSGS. |
| Hodgkin lymphoma, thymoma, atopy | MCD. |
| Heroin, anabolic steroids, sirolimus | FSGS. |
| HBV, syphilis, malaria, SLE, RA, malignancy | MN. |
| Chronic infection, inflammatory disease | AA amyloidosis. |
Workup
| Test | Why |
|---|---|
| UACR/UPCR, albumin, lipids | Confirm phenotype and severity. |
| Hepatitis B/C, HIV | Secondary causes. |
| ANA, C3, C4 | Lupus or immune-complex disease. |
| SPEP/IFE, serum free light chains, UPEP/IFE | Amyloid or monoclonal disease. |
| HbA1c | Diabetes assessment. |
| Anti-PLA2R | Primary membranous nephropathy when positive. |
| Kidney biopsy | Etiology, prognosis and treatment selection. |
Management of complications
| Complication | Practical approach |
|---|---|
| Volume overload | Sodium restriction, loop diuretic +/- thiazide; IV diuretics and albumin in selected refractory cases. |
| Hypertension/proteinuria | RAAS blockade when tolerated; BP target often <130/80. |
| Hypercoagulability | Consider prophylactic anticoagulation in high-risk MN with very low albumin and low bleeding risk; individualize in other etiologies. |
| Hyperlipidemia | Statin if persistent or usual CV indication. |
| Infection risk | Vaccination and prompt infection evaluation. |
| Hypothyroidism | Treat if persistent or symptomatic. |