Graft Survival In Kidney Transplant Recipients Research Articles

426.1: Dyslipidemia in Kidney Transplant Recipients: Is It Time for A Change in Strategy?

Introduction: Dyslipidemia is common in kidney transplant recipients (KTRs), and is associated with a more than 20-fold higher risk of major adverse cardiovascular events compared to the general population. Although KDIGO 2013 guidelines suggest that all KTRs be treated with statins, they are poorly tolerated due to myopathy, hepatotoxicity, and interaction with immunosuppression medications leading to poor compliance. The introduction of the novel lipid-lowering Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors presents an opportunity to treat a significant unmet need in KTRs. Methods: Here we report findings of 3 studies related to hyperlipidemia in KTRs. We conducted a single-center cross-sectional analysis of 250 KTRs about the prevalence of hyperlipidemia, ASCVD scores, frequency of lipid monitoring, and statin use. After our analysis, we performed a nationwide survey using a questionnaire on a lipid management strategy that was sent out to KTR providers and pharmacists. We also conducted a prospective study evaluating PCSK-9 inhibitor (Evolocumab) in the treatment of LDL-cholesterol (LDL-C) levels for KTRs. Patients included in the study were started on Evolocumab 140 mg subcutaneously every 2 weeks and their lipids were checked at 3 months. Results: Our institutional study showed suboptimal lipid control in KTRs with only about 52.3% getting optimal monitoring (Figure 2). This was also seen in the national survey involving 34 centers, where we found disparities and a lack of general consensus in lipid management (Figure 3). With regards to PCSK-9 inhibitor study, all 17 patients with 3 monthly follow-up (n=44 enrolled to date) showed a significant drop in their LDL-C levels (35% to 90%). There was also a remarkable reduction in ASCVD scores. The mean eGFR for all patients was stable (Figure 4). Overall, Evolocumab was well tolerated by all patients.Discussion: Sub-optimal lipid control found at our institution, along with the disparities in the survey responses indicate that there is no uniform strategy in lipid management in KTRs. This could be due to a lack of strong evidence on which the 2013 KDIGO guidelines are based. There is a need for long-term studies to assess the benefits of lipid management on patient and graft survival in KTRs and the development of a clearer, more standardized approach to the management of lipids. In terms of treatment, PCSK-9 inhibitors seem to be very effective for the reduction of LDL-C levels in KTRs. They have a favorable side effect profile and do not interact with immunosuppressive medications. Unlike cardiovascular benefits shown by statins in long-term studies, there is no data regarding PCSK-9 inhibitors as of yet. Given the challenges faced with statins, PCSK-9 inhibitors could be considered the therapy of choice for statin-intolerant patients, if supported by evidence of beneficial cardiovascular outcomes. “Study of safety and efficacy of PCSK-9 inhibitor (Evolocumab) in kidney transplant recipients.” is funded by AMGEN.

HLA Gene Dosage Effect on Renal Allograft Survival

BackgroundHuman leukocyte antigen (HLA)-A, HLA-B, and HLA-DR matching has beneficial long-term effects on renal allograft survival. However, the gene dosage effect of mismatched HLA on transplant outcomes is not known. We investigated the HLA gene dosage effects on allograft survival in kidney transplant recipients (KTRs). MethodsWe analyzed HLA typing of KTRs and kidney donors at Kyungpook National University Hospital from January 1982 to December 2012. KTRs were divided into 2 groups: recipients from homozygous HLA donors and recipients from heterozygous HLA donors. Death-censored graft survival of KTRs was compared according to allele state of kidney donors. ResultsIn this study, 697 KTRs were enrolled. According to Kaplan-Meier analysis, graft survival in KTRs of HLA-DR and HLA-B heterozygous donors was longer than that in KTRs of HLA-DR and HLA-B homozygous donors (P = .007 and P < .0001, respectively). Multivariate Cox proportional hazards model analysis showed that HLA-DR and HLA-B donor homozygosity was an independent risk factor for death-censored graft survival (P = .019 and P = .022, respectively). Death-censored graft survival was not associated with HLA-A and HLA-A, B, DR allele states. ConclusionsCompared with HLA donor mismatch caused by HLA-DR and HLA-B heterozygosity, HLA donor mismatch caused by HLA-DR and HLA-B homozygosity was associated with significantly increased risk of graft failure. In addition to the number of HLA mismatch between KTRs and donors, the donor allele state should be considered to predict transplant outcomes.