Beyond the bladder: Recognising glomerular hematuria and the role of genetic testing in clinical practice

Table 1 Common nephrological causes for hematuria: Clinical features and suggested management for physicians

Renal diagnosis	Urine findings (hematuria and proteinuria)	Systemic/extra-renal features	Family history	Suggested next step
Primary glomerulonephritis
IgA nephropathy	Microhematuria ± episodic macroscopic hematuria (synpharyngitic); mild-moderate proteinuria	Nil specific; often follows upper respiratory tract infection	May be positive	Nephrology referral; urine ACR; serum creatinine/eGFR
Thin basement membrane nephropathy	Persistent microhematuria; proteinuria absent or trace	Nil	Positive - first-degree relatives with hematuria	Nephrology referral; genetic testing (COL4A3/COL4A4) if proteinuria or eGFR decline develops
Alport syndrome (X-linked/AR/AD)	Persistent microhematuria + proteinuria; RBC casts possible	Sensorineural hearing loss; anterior lenticonus; macular flecks	Strongly positive - renal failure, dialysis, or transplant in family	Nephrology referral; genetic testing (COL4A3/ COL4A4/COL4A5); audiology; ophthalmology review
FSGS	Microhematuria + significant proteinuria (nephrotic range possible)	Nephrotic syndrome, hypertension	May be positive (genetic FSGS)	Nephrology referral; urine PCR/ACR; renal biopsy likely needed
Membranous nephropathy	Microhematuria + sub-nephrotic proteinuria	Nephrotic syndrome and/or thromboembolic events	Usually, negative	Nephrology referral; anti-PLA2R antibody; urine ACR
Mesangioproliferative GN	Persistent microhematuria + proteinuria	Nil specific	Usually, negative	Nephrology referral; urine ACR; serum creatinine/eGFR; complement levels
CFHR5 nephropathy	Persistent microhematuria ± synpharyngitic macroscopic hematuria; mild proteinuria	Nil specific	Strongly positive	Nephrology referral; complement studies; genetic testing (CFHR5)
Secondary glomerulonephritis
Lupus nephritis (SLE)	Microhematuria + proteinuria + RBC casts	Malar rash; arthritis; serositis; oral ulcers; photosensitivity; pancytopenia, organomegaly, lymphadenopathy, hypertension	May be positive	Nephrology referral; ANA, anti-dsDNA, complement (C3/C4)
ANCA-associated Vasculitis (GPA/MPA)	Microhematuria + proteinuria; RBC casts; rapidly declining eGFR	Sinusitis; hemoptysis; pulmonary infiltrates; purpura	Usually, negative	Urgent nephrology referral; ANCA (PR3/MPO); chest imaging
Anti-GBM disease	Macroscopic or microscopic hematuria + heavy proteinuria; RBC casts	Hemoptysis; rapidly progressive renal failure	Usually, negative	Emergency nephrology referral; anti-GBM antibody; CXR
IgA vasculitis	Microhematuria ± proteinuria	Palpable purpura (lower limbs/buttocks); arthralgia; colicky abdominal pain	Usually, negative	Nephrology referral; clinical diagnosis; urine monitoring
Post-infectious glomerulonephritis	Macroscopic or microscopic hematuria + proteinuria; RBC casts; oliguria	Preceding streptococcal throat or skin infection (1-3 weeks prior)	Usually, negative	Nephrology referral; ASO titre; C3 (low); C4 (normal)
Complement-mediated
C3 glomerulopathy (C3GN/DDD)	Microhematuria + proteinuria; RBC casts	Nil specific; lipodystrophy in DDD	May be positive (complement gene variants)	Nephrology referral; C3/C4; complement factor H; genetic complement panel
Atypical HUS	Hematuria + proteinuria; rapidly falling eGFR	Thrombocytopenia; microangiopathic hemolytic anemia; hypertension	May be positive (CFH, CFI gene variants)	Emergency nephrology referral; FBC; LDH; complement studies
Hereditary/genetic
ADPKD	Micro or macroscopic hematuria; proteinuria mild or absent	Flank pain; hypertension; enlarged kidneys; hepatic cysts	Strongly positive - autosomal dominant pattern	Renal ultrasound; nephrology referral; PKD1/PKD2 genetic testing if required
Congenital anomalies of kidney and urinary tract	Microhematuria; proteinuria variable	Structural anomaly on imaging; recurrent UTIs	May be positive	Renal ultrasound; nephrology referral; genetic testing if syndromic
Tubulointerstitial
AIN	Microhematuria + mild proteinuria; eosinophiluria (variable)	Drug exposure (NSAIDs, antibiotics, PPIs); fever; rash; rising creatinine	Usually, negative	Nephrology referral; stop offending drug; urgent review if creatinine rising
Oxalate nephropathy	Microhematuria + oxalate crystals on urinalysis; mild proteinuria	High oxalate diet; bariatric surgery history; prior jejunoileal bypass	May be positive (primary hyperoxaluria)	Nephrology referral; 24-hour urine oxalate; genetic testing if primary hyperoxaluria suspected

Source: American Urological Association/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction microhematuria guideline (2020, amended 2025)[3] and standard nephrology classification. AR: Autosomal recessive; AD: Autosomal dominant; FSGS: Focal segmental glomerulosclerosis; GN: Glomerulonephritis; CFHR5: Complement factor H-related 5; SLE: Systemic lupus erythematosus; ANCA: Anti-neutrophil cytoplasmic antibody; GPA: Granulomatosis with polyangiitis; MPA: Microscopic polyangiitis; GBM: Glomerular basement membrane; ADPKD: Autosomal dominant polycystic kidney disease; C3: Complement component 3; C3GN: C3 glomerulonephritis; DDD: Dense deposit disease; HUS: Hemolytic uremic syndrome; AIN: Acute interstitial nephritis; RBC: Red blood cell; eGFR: Estimated glomerular filtration rate; UTI: Urinary tract infection; NSAID: Nonsteroidal anti-inflammatory drug; PPI: Proton pump inhibitor; CFH: Complement factor H; CFI: Complement factor I; ACR: Albumin creatinine ratio; COL4A3: Collagen type IV alpha 3 chain; COL4A4: Collagen type IV alpha 4 chain; COL4A5: Collagen type IV alpha 5 chain; ANA: Antinuclear antibody; dsDNA: Double-stranded deoxyribonucleic acid; C4: Complement component 4; PCR: Protein creatinine ratio; PLA2R: Phospholipase A2 receptor; PR3: Proteinase 3; MPO: Myeloperoxidase; GBM: Glomerular basement membrane; CXR: Chest X-ray; ASO: Anti-streptolysin O; FBC: Full blood count; LDH: Lactate dehydrogenase; PKD1: Polycystic kidney disease 1; PKD2: Polycystic kidney disease 2.