Renal, Fluids, Electrolytes & Acid-Base · Topic 5 of 22

Glomerulonephritis & Nephrotic Syndrome

Renal · glomerular disease

Glomerulonephritis & Nephrotic Syndrome

RBC casts mean nephritic; > 3.5 g/day of protein with edema means nephrotic. AKI with an active sediment needs serologies, a biopsy and urgent treatment.

Key numbers

Nephrotic: proteinuria > 3.5 g/day with edema> 3.5 g/day protein

Pulse methylprednisolone plus cyclophosphamide or rituximabMethylpred 1 g IV × 3–5 d

01 · Defined byNephritic: dysmorphic RBCs and RBC casts

Nephritic syndrome = glomerular inflammation with hematuria (dysmorphic RBCs, RBC or mixed cellular casts) and proteinuria, with or without hypertension, rising creatinine and oliguria.

02 · Defined byNephrotic: proteinuria > 3.5 g/day with edema

Nephrotic syndrome = nephrotic-range proteinuria (> 3.5 g/day) with edema and hypoalbuminemia (often < 2.5 g/dL), typically with hyperlipidemia and lipiduria (oval fat bodies, fatty casts, Maltese crosses).

03 · FirstRPGN: serologies and early biopsy now

AKI over weeks with hematuria and RBC casts suggests rapidly progressive GN: send anti-GBM, ANCA, ANA/anti-dsDNA, ASO, cryoglobulins and C3/C4, and get an early kidney biopsy (crescents in > 50% of glomeruli).

Causes & risk factors

Why it happens

Adult nephrotic: diabetes, FSGS, membranous, minimal changePrimary nephrotic causes are minimal change disease, FSGS and membranous nephropathy (common in adults); diabetes, lupus and amyloidosis are key secondary causes. Biopsy adults when the cause is unclear.

Presentation

What you'll see

Hemoptysis plus GN: pulmonary-renal syndromeGlomerulonephritis with hemoptysis or diffuse alveolar infiltrates is a pulmonary-renal syndrome — anti-GBM disease (Goodpasture syndrome) or ANCA vasculitis such as granulomatosis with polyangiitis.

Diagnosis & monitoring

Work-up

Membranous nephropathy: anti-PLA2R antibodyMembranous nephropathy is PLA2R-antibody positive in the primary form; a negative PLA2R raises concern for a secondary cause such as malignancy. High-risk disease gets rituximab, cyclophosphamide with glucocorticoids, or a calcineurin inhibitor.

Do right now

In this order

First moves

Nephritic: dysmorphic RBCs and RBC casts

→

RPGN: serologies and early biopsy now

→

Pulse methylprednisolone plus cyclophosphamide or rituximabMethylpred 1 g IV × 3–5 d

Why each step

Nephritic: dysmorphic RBCs and RBC castsNephritic syndrome = glomerular inflammation with hematuria (dysmorphic RBCs, RBC or mixed cellular casts) and proteinuria, with or without hypertension, rising creatinine and oliguria.

RPGN: serologies and early biopsy nowAKI over weeks with hematuria and RBC casts suggests rapidly progressive GN: send anti-GBM, ANCA, ANA/anti-dsDNA, ASO, cryoglobulins and C3/C4, and get an early kidney biopsy (crescents in > 50% of glomeruli).

Pulse methylprednisolone plus cyclophosphamide or rituximabTreat RPGN early — ideally before creatinine reaches 5 mg/dL — with methylprednisolone 1 g IV daily for 3–5 days, then prednisone 1 mg/kg, plus cyclophosphamide or rituximab. Untreated, up to 90% reach kidney failure.

Management

Orders

Anti-GBM disease: plasma exchange plus immunosuppressionAnti-GBM disease (linear IgG along the GBM) gets plasma exchange for about 14 days with corticosteroids and cyclophosphamide; outcomes are best when treated before oliguria and with creatinine < 7 mg/dL.

Nephrotic care: ACE inhibitor/ARB, salt restriction, statinManage nephrotic syndrome with an ACE inhibitor or ARB for proteinuria, sodium < 2 g/day, loop diuretics for edema, a statin for dyslipidemia and pneumococcal vaccination; protein restriction is not recommended.

Minimal change disease: prednisone 1 mg/kgMinimal change disease (most childhood and about 15% of adult nephrotic syndrome; linked to NSAIDs and Hodgkin lymphoma) responds to prednisone 1 mg/kg daily for up to 8 weeks in 80–90%, though relapse is common.

IgA nephropathy: RAS blockade plus SGLT2 inhibitorIgA nephropathy, the most common GN worldwide, is treated with an ACE inhibitor or ARB, adding an SGLT2 inhibitor for persistent proteinuria; corticosteroids are added for rising proteinuria or creatinine.

Red flags & don'ts

Avoid harm

Nephrotic syndrome causes venous thrombosis complicationNephrotic syndrome is hypercoagulable (urinary antithrombin III loss, increased hepatic clotting factors): watch for renal vein thrombosis (flank pain, hematuria) and PE, especially in membranous nephropathy; anticoagulate established thrombosis.

Nephritic or nephrotic?

Commonly confused

Urine sediment	Dysmorphic RBCs, RBC casts
Proteinuria	Present, variable
Other features	Hypertension, rising creatinine, oliguria
Classic causes	Postinfectious GN, IgA nephropathy, RPGN
Key complication	Rapid loss of kidney function (RPGN)

Commonly confused

Tell apart

Pauci-immune RPGN is ANCA vasculitisRPGN types: anti-GBM (~20%, linear IgG), immune complex (granular deposits — postinfectious, lupus, IgA) and pauci-immune (no deposits, almost always ANCA-positive: PR3 or MPO).

Low complement points to immune-complex GNLow complement points to immune-complex disease — postinfectious GN, lupus nephritis, membranoproliferative GN, endocarditis (and cholesterol emboli); complement is usually normal in IgA nephropathy.

More detail

Reference

Show 6 reference facts

Rituximab for ANCA-associated RPGN is dosed 375 mg/m² IV weekly for 4 weeks (RAVE) or 1 g repeated after 2 weeks.

Plasma exchange may be considered for ANCA or immune-complex RPGN with alveolar hemorrhage or severe kidney failure at presentation, but a large randomized trial showed no reduction in death or kidney failure.

Postinfectious GN is treated supportively; the prognosis is excellent, and serology (ASO, anti-DNase) plus low C3 usually makes biopsy unnecessary.

Nephrotic urinary protein losses also cause infections (cellulitis, spontaneous bacterial peritonitis), anemia, and a higher levothyroxine requirement from thyroid-binding globulin loss.

Test adults with nephrotic syndrome for secondary causes as indicated: HbA1c, ANA, hepatitis B and C, HIV, serum and urine protein electrophoresis, cryoglobulins and C3/C4.

Before kidney transplant, anti-GBM titers should be undetectable for 12 months, and pauci-immune disease quiescent for 6 months.

Pearl

Blood and casts = nephritic; protein and fat = nephrotic.