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.

Table 2 Pre-test counselling framework for genetic testing in glomerular hematuria

Counselling topic	Standard patient-facing counselling script
Why the test is being done?	This test looks for differences in your genes that can cause kidney disease. We are checking these differences to see if they can explain your symptoms and help us determine best way to care for you
What the results may show?
Positive - pathogenic/Likely pathogenic	This means we found a genetic difference that causes disease and explains your condition
Negative - benign/Likely benign	This means no known disease- causing difference was found. It doesn't always rule out a genetic cause, but we didn’t find one today
Inconclusive	We found a genetic difference, but we aren’t sure yet if it’s the cause of the disease or just a normal variation
So what’s next? How it affects treatment or family	Finding a genetic cause can change your treatment plan, such as suggesting different medication or extra screenings. Because this condition runs in the family it may also help us identify if your relatives are at risk