Pathogenesis of glomerular haematuria

Table 1 Classification of haematuric diseases by histopathological findings

Glomerular endothelial cell layer	GBM disorders	Mesangial deposits	Podocytary slit diaphragm disorders	Subendothelial/subepithelial deposit	Others
ANCA	Primary	IgAN	MYH9 disease	Primary GN	WRN
Endocapillary	Alport	HSP	Fabry disease	MBP	SCD
	TBMD			Endocapillary
	HANAC			Crescentic
	? LPHS
				Secondary GN
	Secondary			SLE
	Anti-GBM disease			Cryoglobulinemia
	C3 glomerulopathy
	CFHR5 nephropathy			Fibrillar deposit
				Fibronectin
				Fibrillary
				Immunotactoid

GBM: Glomerular basement membrane; ANCA: Antineutrophil cytoplasmic antibodies; CFHR5: Complement factor H–related 5 nephropathy; GN: Glomerulonephritis; HANAC: Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps syndrome; IgAN: IgA nephropathy; LPHS: Loin back pain syndrome; MBP: Membranoproliferative; SCD: Sickle cell disease; HSP: Henoch-Schönlein purpura; SLE: Systemic lupus erythematous; TBMD: Thin basement membrane disease; WRN: Warfarin related nephropathy.

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.