Complement related kidney diseases: Recurrence after transplantation

Table 1 Causes of graft loss (living kidney transplantation)

	< 1 yr		> 1 yr
	Non identical	Identical	Non identical	Identical
Acute rejection	5 (41.7%)	0 (0%)
CAN with/without CR	2 (16.7%)	0 (0%)	16 (31.4%)	5 (23.8%)
CNI nephrotoxicity	0 (0%)	0 (0%)	2 (3.9%)	1 (4.8%)
Recurrence of original disease	1 (8.3%)	0 (0%)	10 (19.6%)	6 (28.6%)
Death with functioning graft	2 (16.7%)	1 (50%)	19 (37.3%)	7 (33.3%)
Discontinuation of immunosuppressant	0 (0%)	1 (50%)	4 (7.8%)	1 (4.8%)
Non-compliance	1 (8.3%)	0 (0%)	0 (0%)	1 (4.8%)
Others	1 (8.3%)	0 (0%)	0 (0%)	0 (0%)
P	0.2002		0.6158

CAN: Chronic allograft nephropathy; CR: Chronic rejection; CNI: Calcineurin inhibitor.

Table 2 Risk of atypical hemolytic uremic syndrome recurrence according to the implicated genetic abnormality

Gene	Protein location	Functional impact	Mutation frequency in aHUS (%)	Recurrence frequency after transplantation (%)
Mutation
CFH	Plasma	Loss	20-30	75-90
CFI	Plasma	Loss	2-12	45-80
CFB	Plasma	Gain	1-2	100
C3	Plasma	Gain	5-10	40-70
MCP	Membrane	Loss	10-15	15-20
THBD	Membrane	Loss	5	1 case
Genetic polymorphism (frequency in control population)
Homozygous CFHR1del (3%-8%)	Circulating	Undetermined	14-23 (> 90% in patients with anti-CFH antibodies	NA

aHUS: Atypical hemolytic uremic syndrome; C3: Complement C3; CFH: Complement factor H; CFI: Complement factor I; CFB: Complement factor B; MCP: Membrane cofactor protein; THBD: Thrombomodulin; CFHR1: Complement factor H receptor 1; NA: Not available.

Table 3 Overview of mutations in complement factor H related protein genes

Genetic defect	Phenotypical expression
Duplication in the CFHR5 gene	C3 glomerulopathy (CFHR5 nephropathy)
Duplication in the CFHR1 gene	C3 glomerulopathy
Hybrid CFHR3/CFHR1 gene	C3 glomerulopathy
Hybrid CFHR2/CFHR5 gene	C3 glomerulopathy
Hybrid CFH/CFHR1 gene	aHUS
Hybrid CFH/CFHR3 gene	aHUS

CFHR: Complement factor H related; aHUS: Atypical hemolytic uremic syndrome.