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Background: Acute rejection (AR) is associated with worse renal allograft outcomes. Therefore, this study investigated single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with AR, accounting for center variation, in a multicenter, prospective, observation study., Methods: We enrolled patients from six transplant centers, five in the United States and one in Canada. A total of 2724 SNPs were genotyped. We accounted for center variation in AR rates by stratifying by transplant center and using novel knowledge discovery methods., Results: There was significant center variation in AR rates across the six transplant sites (P<0.0001). Accounting for this difference and clinical factors independently associated with AR, we identified 15 novel SNPs associated with AR with stratification by transplant center (P<0.05). We also identified 15 novel SNPs associated with severity of tubulitis scores, after adjusting for transplant center and other clinical factors independently associated with severity of tubulitis (P<0.05). There was some overlap with one SNP associated with AR and also associated with severity of tubulitis, among the top 15 SNPs., Conclusion: Center-to-center variation is a major challenge to genomic studies focused on AR. The SNPs associated with AR and severity of tubulitis in this study will need to be validated in independent cohort of kidney transplant recipients.

Death with function causes half of late kidney transplant failures, and cardiovascular disease (CVD) is the most common cause of death in these patients. We examined the use of potentially cardioprotective medications in a prospective observational study at seven transplant centers in the United States and Canada. Among 935 patients, 87% received antihypertensive medications at both 1 and 6 months after transplantation. Similar antihypertensive regimens were used for patients with and without diabetes and CVD, but with wide variability among centers. In contrast, while 44% of patients were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) at the time of transplantation, the proportion taking these agents dropped to 12% at month 1, then increased to 24% at 6 months. Fewer than 30% with CVD or diabetes received ACEI/ARB therapy 6 months posttransplant. Aspirin use was uncommon (<40% of patients). Even among those with diabetes and/or CVD, fewer than 60% received aspirin and only half received a statin at 1 and 6 months. This study demonstrates marked variability in the use of cardioprotective medications in kidney transplant recipients, a finding that may reflect, among several possible explanations, clinical uncertainty due the lack of randomized trials for these medications in this population.

The perioperative and long-term risks for living kidney donors are of concern. We have studied donors at the University of Minnesota 20 years or more (mean 23.7) after donation by comparing renal function, blood pressure, and proteinuria in donors with siblings. In 57 donors (mean age 61 [SE 1]), mean serum creatinine is 1.1 (0.01) mg/dl, blood urea nitrogen 17 (0.5) mg/dl, creatinine clearance 82 (2) ml/min, and blood pressure 134 (2)/80 (1) mm Hg. 32% of the donors are taking antihypertensive drugs and 23% have proteinuria. The 65 siblings (mean age 58 [1.3]) do not significantly differ from the donors in any of these variables: 1.1 (0.03) mg/dl, 17 (1.2) mg/dl, 89 (3.3) ml/min, and 130 (3)/80 (1.5) mm Hg, respectively. 44% of the siblings are taking antihypertensives and 22% have proteinuria. To assess perioperative mortality, we surveyed all members of the American Society of Transplant Surgeons about donor mortality at their institutions. We documented 17 perioperative deaths in the USA and Canada after living donation, and estimate mortality to be 0.03%. We conclude that perioperative mortality in the USA and Canada after living-donor nephrectomy is low. In long-term follow-up of our living donors, we found no evidence of progressive renal deterioration or other serious disorders.