STEPTRACKERRENAL | PATHOLOGY + IMMUNOLOGY | HIGH-YIELD REVIEW

Nephrotic Syndrome I — Podocytopathies & Membranous

When the filter leaks protein: the syndrome itself, then minimal change disease, FSGS and membranous nephropathy.

FOCUS ON
Nephrotic = proteinuria > 3.5 g/day, hypoalbuminemia, edema, hyperlipidemia, lipiduria (Maltese crosses), hypercoagulability. Minimal change: children, normal light microscopy, effaced foot processes, steroids work. FSGS: Black and Hispanic adults, HIV, heroin, obesity, poor steroid response. Membranous: anti-PLA2R, spike and dome, SLE, HBV, tumors.
TOPIC
MECHANISM
FINDINGS
CLUE
Nephrotic syndrome
Podocyte or GBM injury → loss of the size/charge barrier
Proteinuria > 3.5 g/day, albumin < 3 g/dL, pitting/periorbital edema, frothy urine
Little or no hematuria
Hyperlipidemia & lipiduria
Low oncotic pressure → ↑ hepatic lipoprotein synthesis; ↓ lipoprotein lipase
↑ cholesterol, TG; fatty casts, oval fat bodies
"Maltese cross" under polarized light
Hypercoagulability
Urinary loss of antithrombin III, protein C/S; ↑ hepatic fibrinogen
Renal vein thrombosis (flank pain, hematuria), DVT, PE
Most often with membranous
Infection risk
Urinary loss of IgG and complement
Spontaneous peritonitis, cellulitis (encapsulated organisms)
Also loss of vitamin D-binding protein, TBG
Minimal change disease
most common in children
T-cell cytokines injure podocytes → effaced foot processes (EM only)
Normal LM, negative IF; selective albuminuria
Excellent response to steroids
Minimal change — triggers
Immune stimulus
Recent infection, immunization, Hodgkin lymphoma, NSAIDs, allergy
Adult MCD → look for lymphoma
FSGS — primary
Podocyte injury (circulating factor, APOL1 risk variants)
Segmental sclerosis and hyalinosis in some glomeruli; effacement on EM
Most common nephrotic cause in Black and Hispanic adults · poor steroid response → ESRD
FSGS — secondary
Adaptive (hyperfiltration) or toxic
HIV (collapsing variant), heroin, sickle cell, obesity, reflux nephropathy, interferon, ↓ nephron mass
Collapsing FSGS = HIV, APOL1
Membranous nephropathy — primary
common in White adults
Antibodies to PLA2R on podocytes → subepithelial immune complexes
Diffuse GBM thickening; spike and dome on silver stain/EM; granular IgG and C3
Anti-PLA2R ⁺ · renal vein thrombosis
Membranous — secondary
Antigen trapped beneath podocytes
SLE (class V), HBV, HCV, solid tumors (lung, colon), drugs (NSAIDs, penicillamine, gold)
Older adult → screen for cancer

Mechanism — leak to edema

Podocyte injuryEffaced foot processes
→
Massive proteinuria
→
Hypoalbuminemia↓ Oncotic pressure
→
Edema+ Na⁺ retention
Liver ↑ lipoproteinsHyperlipidemia

Loss of the GBM's negative charge (heparan sulfate) lets albumin through first — selective proteinuria in minimal change disease.

LM, EM and IF compared

DISEASE
LIGHT
ELECTRON
IF
Minimal change
Normal
Foot process effacement
Negative
FSGS
Segmental sclerosis, hyalinosis
Effacement
Negative or IgM/C3 in scars
Membranous
Thick GBM
Subepithelial deposits, spike and dome
Granular IgG, C3

How it's tested

COMMON CONFUSIONMinimal change and FSGS both show only foot-process effacement on EM. Light microscopy decides: normal glomeruli (MCD) vs segmental scars (FSGS).
THE TRAPSudden flank pain and hematuria in a patient with membranous nephropathy is renal vein thrombosis — from urinary antithrombin III loss.
YOUR APPROACHNephrotic? → age and population → associated condition (lymphoma, HIV, heroin, SLE, HBV, tumor) → biopsy pattern (LM, EM, IF) → steroid response.

If you see… think…

4-year-old with periorbital edema after a cold, normal LM → minimal change disease
Adult nephrotic syndrome + Hodgkin lymphoma → minimal change disease
Black man with HIV and nephrotic syndrome, collapsing glomeruli → collapsing FSGS
Heroin user with heavy proteinuria and scarred glomeruli → FSGS
Spike and dome on EM, anti-PLA2R ⁺ → primary membranous nephropathy
SLE with nephrotic-range proteinuria, subepithelial deposits → lupus class V
Membranous nephropathy in a 65-year-old smoker → screen for solid tumor
Nephrotic patient with sudden flank pain and hematuria → renal vein thrombosis
Maltese crosses in the urine → lipiduria (oval fat bodies)
Steroid-resistant nephrotic syndrome → FSGS