Park, Walter D.

Background Nonadherence to immunosuppression after kidney transplant is an important contributor to graft failure. Little is known about how nonadherence changes 3 years posttransplant when Medicare coverage of immunosuppression ends and how that nonadherence impacts allograft histology. The goal of this study was to compare rates of nonadherence during posttransplant years 1 to 3 to years 3 to 5 and examine the relationship between nonadherence during years 3 to 5 and 5-year allograft histology. Methods We retrospectively analyzed 552 conventional kidney allografts in patients transplanted at our center between January 1, 1999, and June 1, 2010, who used the Mayo Clinic Specialty Pharmacy for the first 5 years posttransplant. Nonadherence was defined as less than 80% proportion of days covered. Overall adherence to immunosuppression appeared to be higher during years 3 and 5 compared to between years 1 and 3 (89.4% vs 82.9%, respectively; P < 0.0001 [paired t test]). Results Overall nonadherence during posttransplant years 3 to 5 appeared to be associated with fibrosis and inflammation on 5-year allograft biopsy but not with transplant glomerulopathy (16.9% vs 5.9%, P = 0.004; 10.4% vs 8.5%, P = 0.61, respectively). After adjusting for nonadherence to calcineurin inhibitor and prednisone therapy, only nonadherence to antimetabolite therapy remained significantly associated with 5-year fibrosis and inflammation (odds ratio, 10.6; 95% confidence interval, 1.5-76.1; P = 0.02). Conclusions Efforts to improve long-term adherence, possibly through the use of specialty pharmacies and increased adherence to antimetabolite therapy, may improve long-term allograft histology and survival, although further studies are needed to confirm these findings.

AbstractThe aim of this study was to investigate correlations between early subclinical findings (10‐ and 90‐day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 −XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells). Inflammation persisted at 90 days and was associated with the development of transplant glomerulopathy by 2 years and graft loss. In contrast, endothelial cell (EC) changes present at 90 days by either electron microscopy or gene expression were not associated with transplant glomerulopathy or graft loss in this cohort. Eculizumab treatment did not appear to alter inflammation or EC changes. Therefore, intragraft inflammation might be an appropriate surrogate marker of progression and also a target of therapy to prevent chronic antibody‐mediated rejection.

AbstractRenal retransplantation after a failed prior kidney and pancreas transplant is being increasingly performed. In these complex cases, both iliac fossae have been used for prior transplants, and the placement of the new allograft can be problematic. We describe our experience with an alternative technique for renal retransplantation (RRTx) in the setting of severe bilateral aortoiliac atherosclerosis or scarring and fibrosis on the iliac vessels. Nephrectomy of the failed allograft is performed, and the renal vessels of the failed allograft (RVFA) are preserved. The new kidney is implanted on RVFA at the same operative time. This technique was attempted and successfully accomplished in a total of six patients (mean operative time = 240 ± 63 min). One postoperative complication occurred: poor arterial inflow to the allograft, being corrected reoperatively. Hospitalizations ranged from five to eight d. Five of the six patients were alive with a functioning allograft at last follow‐up (a single graft failure occurred 21 months postoperatively in the setting of post‐transplant lymphoproliferative disease that also led to patient death). Renal vessels of the failed allograft seem to be suitable alternative vascular conduits for renal retransplantation after prior kidney and pancreas transplants.