LAUSR

Post transplant (pTX) glomerulonephritis (GN) is an important factor contributing to early and late allograft failure. De novo or recurrent IgA GN are the most frequent pTX-GN forms, however little is known about the optimal risk and therapeutic assessment. Recently, immunopathological evidence of glomerular C4d staining has been suggested as a prognostic tool in native glomerular kidney disease, in particular IgA GN. While peritubular capillary C4d is an accepted diagnostic criterion for antibody mediated rejection (ABMR), the role of glomerular C4d in pTX-GN is unkown. The primary hypothesis was that the finding of immunohistochemical glomerular C4d may be associated renal graft survival in post TX IgA GN. This large retrospective cohort study included all indication biopsies performed for cause in 885 kidney allografts from 1999-2006. Cases were screened for biopsy verified de novo or recurrent pTX-GN. GN cases were re-assessed by a single nephropathologist (NK). Primary endpoint was death-sensored graft survival followed until 01.01.2017. The prevalence of pTX-GN was 9.6% (n=85/885). De novo or recurrent IgA-GN was the most common pTX GN form with 40%. Of the 34 cases with pTX IgA GN, 27 had adequate material for interpretation of immunohistochemical glomerular C4d in the biopsy specimen. Eighteen of the 27 cases (66%) with pTx-IgA GN showed positive immunohistochemical C4d staining along glomerular capillary walls. There was no difference in renal function at biopsy or after one year comparing glomerular C4d positive vs. C4d negative pTX IgA GN. In univariate KM analysis glomerular C4d positive pTX-IgA GN showed significantly worse renal allograft survival rates (28%) compared to glomerular C4d negative pTX IgA GN (50%) or cases without GN (66%), p<0.001, respectively. In a multivariate Cox-Regression analysis including baseline covariates as well C4d+ABMR, Borderline lesion and TCMR, C4d+pTX IgA-GN remained independently associated with death censored graft-loss (HR 2.92, 95% CI 1.51-5.64, p=0.001). Glomerular C4d staining in post transplant IgA glomerulonephritis is an independent risk factor for worse allograft survival and may provide a valuable risk assessment tool for prognostic and therapeutic decisions in post transplant glomerulonephritis.