Intravenous Immunoglobulins in the Prevention of Rejection of a Second or Third Kidney Graft

BACKGROUND: Intravenous immunoglobulin (IVIg) reduces acute rejection episodes in kidney transplantation, but adverse events (AEs) are common. The aim of this study was to assess whether human IVIg enhances immunosuppressive effects without increasing AEs in the prevention of acute kidney graft rejection. METHODS: Patients receiving a second or third kidney graft were treated with standard immunosuppressant therapy with (n = 18) or without (n = 10) IVIg. The primary efficacy endpoint was biopsy-proven acute rejection (BPAR) rate at 3 months, and secondary endpoints included acute rejection rate at 12 months, intensity of rejection, and patient survival. RESULTS: Patients in the experimental arm received 3 infusions of IVIg. The BPAR rate decreased with IVIg versus standard immunosuppression alone over 12 months of follow-up. Experimental versus control rates of survival without BPAR were 94% versus 63% and 82% versus 63% at 3 and 12 months. The intensity of the acute rejection episodes (BANFF 97 grade) was similar between groups. One patient from each group died during the 12-month follow-up period. Treatment-emergent AEs were reported in 100% and 94.4% of the control and experimental arms. Most AEs were considered unrelated or unlikely to be related to treatment. CONCLUSIONS: This study supports the efficacy and safety of IVIg in highly sensitized transplant patients for improving transplant rates and reducing graft rejection episodes

Genome-wide Association Study of Acute Renal Graft Rejection.

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls, on Illumina 2.5 M arrays. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant SNPs from the discovery cohort. In the discovery cohort, we found 5 candidate loci tagged by a number of contiguous SNPs (>5) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signalling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium. This article is protected by copyright. All rights reserved