Table 2.
Possible pathogenic mechanisms of haematuria
| Disease | Molecular defect | Prevalence | Main glomerular defect |
Clinical expression |
||
| Haematuria | Proteinuria | CKD progression | ||||
| Genetic disorder | ||||||
| GFB structural damage | ||||||
| Structural GBM damage | ||||||
| ALPORT | X-linked: COL4A5 AR: COL4A3/COL4A4 | 1/50000 | GBM | MH | Variable | 100% approximately 20-30 yr |
| TBMD | COL4A3/COL4A4 | 1% | GBM | MH | Usually absent | 20% CKD |
| HANAC | COL4A1 | 3 families | GBM | MH or gross | Not described | Variable |
| Structural podocyte damage | ||||||
| MYH9 | Non muscle myosin IIA heavy chain | 1:100000 | None | MH | Variable | ESRD by young adulthood |
| Storage disorders | ||||||
| Fibronectine GN | Fibronectin | 44 cases | Mesangial/subendoth | 60% MH | 93% variable degree | ESRD at 20-60 yr |
| Fibrillary | 10-30 nm fibrils | Rare | Mesangial /GBM | MH 47%-73% Gross 5% | Present 41%-55% nephrotic | 50% ESRD in few years |
| Immunotactoid | > 30 nm fibrils | 10-fold rarer than FGN | Mesangial/subepith/subendoth | MH 80% | 100% | 17% ESRD in 3 yr |
| Fabry’s disease | Lysosomal storage | 1:3100- 1:1600 | All the cells | MH | Usually nephrotic | ESRD after age 50 yr |
| Complement mediated | ||||||
| C3 glomerulopathy | Alternative pathway | 1-2 × 106 | Mesangial/GBM | MH 87% | 38% | Variable |
| Inflammatory disorders | ||||||
| Autoimmune | ||||||
| ANCA | Ab vs endothelium | 10-20 × 106 | Endothelium | MH | Variable | Variable |
| Anti GBM | Ab vs COL4 | 0.5-1 × 106/yr | GBM | MH | Variable | Variable |
| Infections (endocapillary) | ||||||
| Primary GN (IgAN, membranoproliferative, crescentic) | ||||||
| IgAN | Galactose-deficient IgA1 | 10%-16% | Mesangial | MH always 75% gross | Rare nephrotic Usual proteinuria | 20% ESRD 20 yr after diagnosis |
| Miscellaneous | ||||||
| WRN | Unknown | 16.5% non-CKD 33% CKD | None | Usually MH | None | Accelerated CKD progression |
| LPHS | Unknown | Unknown | GBM (?) | MH or gross | Absent or minimal | GFR > 60 |
ANCA: Antineutrophil cytoplasmic antibodies; AR: Autosomal recesive; CKD: Chronic kidney disease; COL4A1: Alpha 1 chain of type IV collagen; COL4A3: Alpha 3 chain of type IV collagen; COL4A4: Alpha 4 chain of type IV collagen; COL4A1: Alpha 1 chain of type IV collagen; ESRD: End stage renal disease; GFB: Glomerular filtration barrier; GFR: Glomerular filtration rate; HANAC: Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps syndrome; IgAN: IgA nephropathy; LPHS: Loin back pain haematuria syndrome; MH: Microscopic haematuria; TBMD: Thin basement membrane disease; WRN: Warfarin related nephropathy.