Introduction. Recipients who develop KTx GD may have reduced function and higher risk of graft loss. Using protocol and clinical biopsies we sought to determine the incidence of non-alloimmune mediated KTx GD, risk factors associated with GD and the impact of GD type on graft survival.

Methods. Included are 1435 adult KTx between 1998-2010, 51+14 years old, 62% males and 75% living donor KTx. Induction: thymoglobulin (71%), alemtuzumab (combined with steroid free, 6%) or anti-CD25 (15%). 86% received Tacrolimus. Post-KTx GD was diagnosed by clinical or protocol biopsies done at 4, 12, 24, 60 and 120 months. Follow up 91+43 months. Transplant glomerulopathy was not included as a KTx GD.

Results. Pre-KTx, 490 of 1435 recipients had glomerulonephritis (GN, 34%) and 346 (24%) diabetes. Post-KTx, 229 of 1435 recipients developed GD (16%). The cumulative incidence of GD was 4%, 16%, 19% and 26% at 1, 3, 5 and 10 years, respectively. KTx GD included: FSGS, 88 (38%); IGAN, 55 (24%); membranous (MN), 19 (8%); MPGN, 22 (10%); mesangial proliferative GN (often with C1q), 16 (7%); diabetic glomerulosclerosis (DGS), 20 (9%); and other GDs, 9 (4%). 132 of 229 GDs (58%) were recurrent. The risk of KTx GD increased in: younger recipients (HR=0.83, p<0.0001, every 10 years), females (HR=1.61, p=0.001), alemtuzumab/steroid free (HR=1.87, p=0.007) and lower serum albumin pre-KTx (HR=0.73, p=0.048) (multivariate Cox). Death-censored graft losses occurred in 245 recipients (17%) and 53 of these losses (22%) were due to GD. As a time dependent variable GD increased the risk of graft loss (HR=2.66 (1.97-3.60), p<0.0001) independent of recipient age, HLA mismatches, DSA at transplant and one year graft function and proteinuria. The risk of graft loss varied with the type of GD: MPGN (HR=6.67, p<0.0001), DGS (HR=5.04, p<0.0001), FSGS (HR=2.82, p<0.0001) and IGAN (HR=1.93, p=0.035). Other GD, including MN, did not relate significantly to graft loss.

Discussion. The incidence of GD increases progressively post-KTx, particularly in young, female recipients and in recipients treated with alemtuzumab/steroid free immunosuppression. GD is an important independent risk factor for KTx survival, causing 22% of losses. Risk of graft loss is highest in grafts with MPGN, DGS, FSGS and IGAN. We postulate that early diagnosis and treatment of KTx GD offers opportunities to improve graft survival.

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