Differential Diagnosis for Painless Hematuria with Proteinuria

Single Most Likely Diagnosis

IgA Nephropathy (Berger's Disease)
- Most common primary glomerulonephritis worldwide
- Classically presents with painless hematuria, often after upper respiratory infection
- Variable proteinuria, ranging from mild to nephrotic range
- More common in young adults, with male predominance
- Diagnosis confirmed by kidney biopsy showing mesangial IgA deposits

Membranous Nephropathy
- Primary cause of nephrotic syndrome in adults
- Typically presents with significant proteinuria and microscopic hematuria
- Can be primary (idiopathic) or secondary to medications, infections, autoimmune diseases, or malignancy
Lupus Nephritis
- Renal manifestation of systemic lupus erythematosus (SLE)
- Often presents with proteinuria and hematuria
- Associated with other symptoms of SLE (rash, joint pain, fatigue)
- More common in women of childbearing age
Thin Basement Membrane Disease (Benign Familial Hematuria)
- Characterized by persistent microscopic hematuria with minimal proteinuria
- Benign course with excellent prognosis
- Often familial with autosomal dominant inheritance
- Diagnosis confirmed by electron microscopy showing thinning of glomerular basement membrane
Post-Infectious Glomerulonephritis
- Follows streptococcal or other infections
- Typically presents with hematuria, proteinuria, and often hypertension
- More common in children but can occur in adults
- Usually self-limited with good prognosis

Rapidly Progressive Glomerulonephritis (RPGN)
- Can be caused by ANCA-associated vasculitis, anti-GBM disease, or immune complex disease
- May initially present with just hematuria and proteinuria before rapid decline in renal function
- Requires urgent diagnosis and treatment to prevent irreversible kidney damage
- Red flags include rising creatinine and active urinary sediment
Malignancy (Bladder, Renal, Prostate Cancer)
- Especially in older adults or those with risk factors (smoking, chemical exposures)
- Bladder cancer classically presents with painless hematuria
- Proteinuria may be present due to paraneoplastic glomerulonephritis
- Higher suspicion in patients >40 years old with risk factors
Renal Vein Thrombosis
- Associated with nephrotic syndrome, hypercoagulable states, or malignancy
- Can present with hematuria and significant proteinuria
- May cause acute kidney injury if bilateral or in a solitary kidney
- Requires prompt anticoagulation
Amyloidosis
- Can present with proteinuria and microscopic hematuria
- Associated with chronic inflammatory conditions, multiple myeloma, or hereditary forms
- Progressive disease that can lead to end-stage renal disease
- Often has multi-organ involvement

Alport Syndrome
- Hereditary disorder affecting glomerular basement membranes
- Progressive disease with hematuria, proteinuria, and eventual hearing loss
- X-linked inheritance most common, affecting males more severely
- Diagnosed through genetic testing or kidney biopsy
Fabry Disease
- X-linked lysosomal storage disorder
- Can present with proteinuria and hematuria in early stages
- Associated with neuropathic pain, angiokeratomas, and cardiac abnormalities
- Diagnosed by enzyme assay or genetic testing
C3 Glomerulopathy
- Rare disorder characterized by C3 deposition in glomeruli
- Presents with variable proteinuria and hematuria
- Associated with abnormalities in complement regulation
- Diagnosis confirmed by kidney biopsy with immunofluorescence studies
Hereditary Nephritis (non-Alport)
- Various rare genetic disorders affecting kidney structure
- Can present with persistent hematuria and variable proteinuria
- Often diagnosed through genetic testing
- May have syndromic features depending on the specific disorder