Laura Braun

Incidence and risk factors of glucose metabolism disorders in kidney transplant recipients: role of systematic screening by oral glucose tolerance test.

Background. New-onset diabetes after transplantation (NODAT) increases infectious and cardiovascular complications and reduces patient and graft survival. We assessed the incidence and the risk factors for glucose metabolism abnormalities before and after kidney transplantation using an oral glucose tolerance test (OGTT). The purpose of the study was to better identify patients at risk for NODAT to adapt their immunosuppressive treatment and their management after transplantation. Methods. OGTT was performed before transplantation in 243 patients placed on the kidney waiting list between January 1, 2005, and December 31, 2008. Of these 243 patients, 120 received a kidney transplant and also had an OGTT after transplantation. Results. Impaired glucose tolerance (IGT) was identified in 22 of 120 patients (18%) before transplantation. After transplantation, diabetes developed in 31 patients and 16 patients had IGT. According to univariate analyses, risk factors for NODAT were age more than 50 years, body mass index more than 25 kg/m2, pretransplant IGT, autosomal dominant polycystic kidney disease, and acute rejection. According to multivariate analyses, pretransplant IGT (relative risk=2.4), autosomal dominant polycystic kidney disease (relative risk=3), and acute rejection (RR, 2.8) remained significantly associated with NODAT. Patients were stratified by age, primary kidney disease, and pretransplant OGTT. The risk of developing NODAT increased 2.4-, 5-, and 14-fold, depending on the number of risk factors. Conclusion. Pretransplant OGTT, together with age and nephropathy, is a helpful tool for identifying patients at risk for NODAT. For patients with two or three of these risk factors, the adjustment of immunosuppression may be recommended.

B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

FSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7-1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7-1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7-1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7-1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7-1 blockade did not induce FSGS remission after transplant in our study.

Recent changes in chronic kidney disease-mineral and bone disorders (CKD-MBD) and associated fractures after kidney transplantation.

Background The management of chronic kidney disease–mineral and bone disorders has recently changed. We investigated the modifications of chronic kidney disease–mineral and bone disorder with a special focus on the incidence of fractures in the first year after kidney transplantation (KT). Methods We retrospectively compared 2 groups of patients who consecutively underwent transplantation at our center 5 years from each other. Group 1 consisted of patients (n = 152) transplanted between 2004 and 2006, whereas patients in group 2 (n = 137) underwent KT between 2009 and 2011. Results During the end-stage renal disease phase at the time of transplant, cinacalcet, and native vitamin D were used significantly more frequently in group 2. Median intact parathyroid hormone levels were lower and severe hyperparathyroidism decreased significantly. Vitamin D deficiency dropped from 64% to 20%. After transplantation, persistent hyperparathyroidism (parathyroid hormone > 130 ng/L) and bone turnover markers were significantly reduced in group 2. Native vitamin D supplementation increased over time, whereas the use of active vitamin D was unchanged. The 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly higher. The fracture incidence at 1 year decreased significantly (3.1% vs 9.1%; P = 0.047). No steroid sparing was observed in group 2. Bisphosphonates after KT were more frequently used in group 2. Conclusions Recent changes in clinical practice are associated with reductions in pretransplant and posttransplant hyperparathyroidism, vitamin D deficiency, and fracture risk after KT.

Pre-existing donor-specific antibodies are detrimental to kidney allograft only when persistent after transplantation

Donor‐specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty‐seven patients (15.5%) had pre‐existing DSA detected the day of transplantation. After 5 years, the pre‐existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody‐mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation.

0361: Impaired P2Y12 inhibition by clopidogrel in patients with kidney transplantation

Introduction Several studies have indicated that impaired GFR is an important predictor factor associated with impaired platelet inhibition by clopidogrel. In chronic kidney disease, the presence of low platelet inhibition by clopidogrel is associated with adverse outcome following PCI and stenting. In the present study, we sought to determine if renal transplantation per se alters clopidogrel pharmacodynamics. Patients and methods 36 patients with kidney transplantation were enrolled in one single center (Nephrology Department, Hopitaux Universitaires de Strasbourg). Control patients were 126 patients with different degrees of chronic renal failure, tested in the same conditions. Inclusion criteria were patients under clopidogrel treatment of 75mg per day for at least 8 days. Unstable patients or those presenting with any conditions that could account for reduced platelet inhibition by clopidogrel (heart failure, shock) were excluded. Treatment and medical history were collected at inclusion. Clopidogrel pharmacodynamics was studied using the VASP assay. Results Patients with kidney transplantation were younger (58.3 vs 72.6 years, p Conclusion In kidney transplantation patients treated by clopidogrel, impaired platelet inhibition exist, even after adjustment on estimated glomerular filtration rate. The mechanisms by which immunosuppressive treatments may alter clopidogrel pharmacodynamics requires further investigation