Clinical Images
Before we start…
A 6-year-old has a puffy face, 4+ protein on dipstick, cholesterol 350. No blood in the urine.
Nephrotic or Nephritic?
The glomerulus is a filter. It can fail in exactly two ways:
That's the whole thing. Protein leaking vs blood breaking through. Everything else is downstream of this one distinction.
💧 Nephrotic · "Leaky Sieve"
🩸 Nephritic · "Angry Filter"
Why edema in nephrotic? Lost albumin = low oncotic pressure = fluid leaks into tissues. Why hypertension in nephritic? Inflammation = salt/water retention + reduced GFR.
These are the heavy hitters. Boards love all five.
Who: Children (2-6 yo). Also: NSAIDsNSAIDs reduce prostaglandin-mediated blood flow to the glomerulus. The resulting ischemia can trigger podocyte injury → minimal change pattern., Hodgkin lymphomaHodgkin releases cytokines (IL-13) that damage podocyte foot processes. If an adult presents with MCD, screen for lymphoma..
Biopsy: Light microscopy is normal (that's the "minimal change"). EM shows foot process effacement · the podocytes flatten out.
Treatment: Steroids · responds dramatically. If it doesn't, rethink the diagnosis.
Board clue: Kid + nephrotic + responds to steroids = MCD until proven otherwise.
Who: African Americans (#1 cause of nephrotic in AA), HIV, heroin use, obesity, sickle cell.
Biopsy: Focal (some glomeruli) + segmental (part of a glomerulus) sclerosis on LM. EM shows foot process effacement (like MCD but with sclerosis).
Why boards test it: It's the most common primary nephrotic syndrome in African American adults. HIV-associated nephropathy = FSGS.
Response to steroids: Poor (unlike MCD). This is a key differentiator.
Who: #1 nephrotic in adults overall. Associations: HBVHepatitis B antigens deposit in the subepithelial space, forming immune complexes that thicken the basement membrane., SLE (class V), solid tumors, anti-PLA2R antibodiesPhospholipase A2 receptor antibodies · present in ~70% of primary membranous. The target antigen sits on podocytes. This is the diagnostic serologic marker..
Biopsy: "Spike and dome" pattern on silver stain. Subepithelial deposits (between podocyte and GBM). Diffuse thickening of GBM.
Board clue: Adult + nephrotic + subepithelial deposits = membranous. If they mention anti-PLA2R, it's basically free points.
Who: Long-standing diabetes (type 1 or 2). Most common cause of nephrotic syndrome AND ESRD in the US.
Biopsy: Kimmelstiel-Wilson nodulesNodular glomerulosclerosis · round, acellular, eosinophilic nodules in the mesangium. Pathognomonic for diabetic nephropathy. Named after the two pathologists who described them in 1936. (nodular glomerulosclerosis). Diffuse GBM thickening + mesangial expansion.
Progression: Microalbuminuria → overt proteinuria → nephrotic syndrome → ESRD. ACE inhibitors slow progression (reduce intraglomerular pressure).
Board clue: Diabetic for 15+ years + proteinuria = diabetic nephropathy. Don't overthink it.
What: Misfolded proteins (amyloid) deposit in the kidney (and other organs). AL (primary, from plasma cells) or AA (secondary, from chronic inflammation like RA).
Biopsy: Congo red stain → apple-green birefringence under polarized light. That's the pathognomonic finding.
Board clue: Nephrotic syndrome + multiple organ involvement (big tongue, carpal tunnel, heart failure) + Congo red positive = amyloidosis.
These are the angry, bloody ones. The filter is inflamed.
Key fact: Most common glomerulonephritisGlomerulonephritis = inflammation of the glomeruli. All nephritic diseases are forms of GN. The "-itis" suffix = inflammation = blood getting through. worldwide. Usually young adults.
Presentation: Gross hematuria DURING or within days of a URI (synpharyngitic · happens simultaneously, NOT weeks later).
Biopsy: Mesangial IgA depositsIgA is the mucosal antibody (gut, respiratory). During infection, IgA production surges. Abnormal IgA1 isn't cleared → deposits in the mesangium → inflammation → hematuria. on immunofluorescence.
Complement: Normal (not consumed in this process).
HSP connection: Henoch-Schonlein PurpuraHSP is the systemic form of IgA nephropathy. Same IgA deposits, but also in skin vessels (purpura), joints, GI tract. Think: IgA nephropathy is Berger disease (kidney only), HSP is Berger disease + everything else. = systemic IgA vasculitis. Same kidney findings, but add purpura + arthritis + abdominal pain.
Who: Kids (6-10 yo), 2-4 weeks AFTER Group A Strep pharyngitis or skin infection.
Key timing: AFTER, not during. This is the #1 differentiator from IgA (which is during/synpharyngitic).
Biopsy: "Lumpy bumpy" subepithelial depositsImmune complexes (antibody-antigen from the strep infection) deposit on the outer surface of the GBM. They're irregular = lumpy bumpy on immunofluorescence. Granular pattern. on IF. Enlarged, hypercellular glomeruli on LM.
Labs: Low C3 (complement consumed), elevated ASO/anti-DNase BASO (anti-streptolysin O) rises after pharyngitis. Anti-DNase B rises after skin infections. These confirm prior strep infection, not active infection..
Prognosis: Kids almost always recover fully. Adults have worse outcomes.
What: Rapid loss of kidney function (days to weeks). The most aggressive form of GN.
Biopsy: Crescents on light microscopy · proliferating parietal cells and macrophages in Bowman's space.
Three types:
- Type I · Anti-GBM (GoodpastureAnti-GBM antibodies attack type IV collagen in the glomerular AND alveolar basement membranes. Kidney + lungs. Linear IF pattern. Young men who smoke are classic.): Linear IF pattern. Lungs + kidneys.
- Type II · Immune complex: Granular IF pattern. Caused by SLE, IgA, post-strep going bad.
- Type III · Pauci-immune (ANCA-associatedPauci-immune = few/no immune deposits on IF. The damage is from neutrophils activated by ANCA antibodies (c-ANCA in GPA, p-ANCA in MPA/EGPA). "Pauci" = the IF is deceptively quiet while the kidney is being destroyed.): Negative/few deposits on IF. GPA (c-ANCA), MPA (p-ANCA).
Board clue: Rapidly worsening renal function + crescents on biopsy = RPGN. Then use IF pattern to identify the type.
What: Defective type IV collagenType IV collagen is the structural protein of ALL basement membranes · kidney, eye, ear. That's why Alport hits all three. The mutation makes the GBM progressively thin → split → fail. · the stuff basement membranes are made of.
Inheritance: Most commonly X-linked (boys hit harder, carrier moms may have mild hematuria).
Triad: Nephritis + sensorineural hearing loss + eye abnormalities (anterior lenticonus).
EM: "Basket-weave" splitting of the GBM.
Board clue: Young male + hematuria + hearing loss = Alport. Don't overthink it.
A patient shows up with edema. Let's figure out what they have. You answer, THEN the tree reveals.
Four diseases. Clinical clues eliminate one at a time. Can you find the last one standing?
Drag each feature to where it belongs: NEPHROTIC, NEPHRITIC, or BOTH.
Ten glomerulopathies. Each one has a single fingerprint that nails it on boards. Tap to flip.
Nephrotic Syndrome (>3.5g/day proteinuria)
Minimal Change Disease
- Who: children (most common nephrotic in kids)
- LM: normal (hence "minimal change")
- EM: effacement of foot processes (podocyte injury)
- IF: negative
- Treatment: steroid-responsive (excellent prognosis)
- Board pearl: lipoid nephrosis, triggered by viral URI or NSAIDs
Focal Segmental Glomerulosclerosis
- Who: HIV, obesity, heroin, AA children, sickle cell
- LM: sclerosis in some (focal) glomeruli, in part (segmental) of the glomerulus
- EM: foot process effacement
- Treatment: poor steroid response, often progresses to ESRD
- Board pearl: HIV patient + heavy proteinuria = FSGS (not MCD)
Membranous Nephropathy
- Who: adults, associated with SLE, HBV, solid tumors, penicillamine
- LM: thickened GBM, spikes on silver stain
- EM: subepithelial immune complex deposits (spike and dome)
- IF: granular IgG + C3 along GBM
- Board pearl: most common nephrotic in adults; anti-PLA2R = primary
Diabetic Nephropathy
- Who: DM type 1 and 2 after years of poor control
- LM: Kimmelstiel-Wilson nodules (pathognomonic), diffuse mesangial expansion, thick GBM
- First sign: microalbuminuria (30-300 mg/day)
- Treatment: ACE-i or ARB (renoprotective, reduces proteinuria)
- Board pearl: most common cause of ESRD in the US
Amyloidosis
- Who: multiple myeloma (AL), chronic inflammatory disease (AA)
- LM: amyloid deposits in mesangium, Congo red stain positive
- Under polarized light: apple-green birefringence (pathognomonic)
- EM: fibrillary deposits 8-10 nm
- Board pearl: multiple myeloma workup finds amyloid
Nephritic Syndrome (hematuria + proteinuria + hypertension)
IgA Nephropathy (Berger Disease)
- Who: young adults, often Asian; most common GN worldwide
- Trigger: hematuria within 1-2 days of URI (synpharyngitic)
- IF: mesangial IgA deposits
- Complement: normal C3 (no complement consumption)
- Board pearl: PSGN hematuria comes 2-3 weeks after strep, IgA comes in days
Post-streptococcal GN
- Who: child 2-3 weeks after pharyngitis or impetigo
- Labs: low C3, normal C4, elevated ASO/anti-DNase B
- EM: subepithelial humps ("humps" = post-infectious)
- IF: granular IgG + C3 ("lumpy-bumpy")
- Board pearl: self-limited in children; adults have worse prognosis
Rapidly Progressive GN
- Biopsy: crescents (proliferating parietal cells) in >50% of glomeruli
- Type 1: anti-GBM (Goodpasture), linear IgG IF
- Type 2: immune complex (SLE, IgA, PSGN), granular IF
- Type 3: pauci-immune (ANCA vasculitis), no IF deposits
- Board pearl: fastest-progressing GN, days to weeks to dialysis
Goodpasture Syndrome
- Antibody: anti-GBM targeting collagen IV (alpha-3 chain)
- Clinical: pulmonary hemorrhage + rapidly progressive GN
- IF: linear IgG staining along GBM (pathognomonic)
- Treatment: plasmapheresis + steroids + cyclophosphamide
- Board pearl: linear IF = Goodpasture. Granular IF = immune complex.
Alport Syndrome
- Genetics: X-linked, type IV collagen defect (COL4A5)
- Triad: hematuria + sensorineural hearing loss + eye abnormalities
- EM: "basket-weave" or "moth-eaten" GBM thinning/thickening
- Prognosis: progresses to ESRD, worse in males
- Board pearl: family history of renal failure + deafness = Alport
Work through the clues the same way boards expects you to. Tap a branch to expand it.
Full clinical vignettes with structured labs, five answer choices, and per-option explanations. Read the stem like a real case, form your answer, then check.