IgA Nephropathy

Why IgA nephropathy is correct

• IgA nephropathy is the most common primary glomerulonephritis (GN) worldwide
• KEY DISTINGUISHING FEATURE: synpharyngitic hematuria — gross hematuria occurs concurrent with or within days of a URI, NOT weeks later
• Diagnosis is confirmed by kidney biopsy showing mesangial IgA deposits on immunofluorescence
• Treatment (KDIGO 2025): an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) titrated to the maximum tolerated dose, aiming for proteinuria <0.5 g/day and ideally <0.3 g/day; rapidly progressive (crescentic) disease is treated like ANCA vasculitis with glucocorticoids plus cyclophosphamide

Why the others are wrong

• Post-streptococcal glomerulonephritis — hematuria follows strep throat by about 1–3 weeks (typically about 10 days) or strep impetigo by 3–6 weeks, not concurrent with the URI
• Thin basement membrane disease — benign familial hematuria causes persistent MICROSCOPIC hematuria with normal creatinine and no significant proteinuria, and biopsy shows a thinned GBM without IgA
• Alport syndrome — hereditary (usually X-linked) collagen IV disease with sensorineural hearing loss and ocular defects; biopsy shows basket-weave GBM splitting, not mesangial IgA
• Granulomatosis with polyangiitis — upper-airway symptoms with glomerular hematuria and an elevated creatinine can suggest this ANCA vasculitis, but GPA causes persistent sinonasal disease (chronic sinusitis, epistaxis, nasal crusting), often lung nodules, and a progressive pauci-immune crescentic GN, not brief bouts of gross hematuria that recur with each viral URI

Why Immunoglobulin A nephropathy is correct

• Dysmorphic red cells with proteinuria place the bleeding in the glomerulus, and normal C3 and C4 point to a normocomplementemic glomerular disease, which makes active proliferative lupus nephritis much less likely.
• IgA nephropathy is the most common primary glomerulonephritis worldwide; it peaks in the second and third decades and is more common in men in US and European cohorts.
• Besides gross hematuria during a mucosal infection, its other common presentation is this one: persistent, asymptomatic microscopic hematuria, often with low-grade proteinuria, found on a screening urinalysis.
• New hematuria after a documented normal urinalysis points to an acquired lesion rather than an inherited type IV collagen disorder, and the proteinuria and stage 1 hypertension fit IgA nephropathy rather than benign hematuria.

Why the others are wrong

• Thin basement membrane disease - This inherited thinning of the glomerular basement membrane (often a heterozygous COL4A3 or COL4A4 variant) causes persistent isolated microscopic hematuria that is typically present from childhood, with normal blood pressure, little or no proteinuria, and preserved kidney function; 0.7 g/g of proteinuria and stage 1 hypertension, plus hematuria that was absent at 18, argue against it (the trap is calling all asymptomatic microscopic hematuria in a young adult benign familial hematuria).
• Primary membranous nephropathy - This autoimmune podocyte disease (anti-PLA2R antibodies in most cases) usually presents as nephrotic syndrome (heavy proteinuria, edema, hypoalbuminemia) in middle-aged and older adults; microscopic hematuria can accompany it but does not dominate, so a hematuria-predominant dysmorphic sediment with only 0.7 g/g of proteinuria in a 27-year-old points to a nephritic-leaning lesion instead (the trap is reading any hematuria plus proteinuria in an adult as membranous).
• Lupus nephritis (class III) - Focal proliferative lupus nephritis does cause dysmorphic hematuria, subnephrotic proteinuria, and hypertension in young adults, but it arises in systemic lupus erythematosus, which is about 9 times more common in women and usually brings extrarenal features (rash, arthritis, serositis, cytopenias) with positive ANA and anti-double-stranded DNA antibodies; active proliferative lupus nephritis usually lowers C3 and C4, so normal complements in a well man with an unremarkable examination point elsewhere (the trap is skipping the complement split when sorting glomerular hematuria).
• ANCA-associated glomerulonephritis - This pauci-immune necrotizing glomerulonephritis also leaves C3 and C4 normal and causes dysmorphic hematuria with subnephrotic proteinuria, but it most often affects older adults and typically presents as rapidly progressive glomerulonephritis with a rising creatinine, often with systemic or extrarenal features (fever, weight loss, sinus or pulmonary disease) and positive MPO- or PR3-ANCA; months of stable hematuria with a normal creatinine in a well 27-year-old point elsewhere (the trap is treating every normocomplementemic glomerular sediment as vasculitis).

Additional high-yield points

• Only a kidney biopsy confirms the diagnosis, showing dominant or codominant mesangial IgA on immunofluorescence; serum IgA is elevated in some patients but is neither sensitive nor specific, and no serum or urine biomarker is validated for diagnosis.
• KDIGO 2025 advises considering a kidney biopsy in any adult with proteinuria of 0.5 g/day or more in whom IgA nephropathy is possible, so this patient warrants nephrology referral; isolated glomerular hematuria with less proteinuria, normal blood pressure, and normal eGFR is usually monitored rather than biopsied.
• Normal complements: IgA nephropathy, thin basement membrane disease, Alport syndrome, primary membranous nephropathy, ANCA-associated glomerulonephritis, and anti-glomerular basement membrane disease. Low complements: post-infectious glomerulonephritis, lupus nephritis, C3 glomerulopathy or membranoproliferative glomerulonephritis, and cryoglobulinemia.
• The other classic presentation is synpharyngitic gross hematuria within 1 to 3 days of an upper respiratory infection; post-streptococcal glomerulonephritis follows pharyngitis by 1 to 3 weeks and lowers C3.
• Supportive care (KDIGO 2025): an ACE inhibitor or ARB titrated to the maximum tolerated dose for all patients with IgA nephropathy without a contraindication (the 2021 recommendation applied to proteinuria above 0.5 g/day); for patients at risk of progression (proteinuria of 0.5 g/day or more) it also suggests an SGLT2 inhibitor (started at eGFR 20 or above, per KDIGO 2024 CKD) and sparsentan (a dual endothelin-angiotensin receptor antagonist), which replaces the ACE inhibitor or ARB and is never combined with it; the proteinuria goal is below 0.5 g/day, ideally below 0.3 g/day.
• Heterozygous COL4A3 or COL4A4 variants, the usual cause of thin basement membranes, are now grouped in the Alport spectrum; some carriers later develop proteinuria and CKD, so their hematuria is monitored long term. Males with X-linked Alport syndrome have microscopic hematuria from infancy, so a normal urinalysis in adolescence effectively excludes it.