Comparing survival outcomes for kidney transplant recipients with pre-existing diabetes versus those who develop post-transplantation diabetes.

INTRODUCTION: The aim of this study was to compare the management strategy and clinical outcomes for kidney transplant recipients with pre-transplant versus post-transplantation diabetes (PTDM) in a contemporary cohort. METHODS: This is a single-centre, retrospective. observational study of kidney transplant recipients between 2007 and 2018 with follow-up to 31 December 2020. Data were extracted from hospital electronic patient records, with clinical outcomes linked to national data sets. PTDM was diagnosed by international consensus guidelines. Unadjusted and adjusted survival outcomes were assessed with Kaplan-Meier curves and Cox regression models, respectively, with PTDM handled as a time-varying covariate. RESULTS: Data were analysed for 1,757 kidney transplant recipients, of whom 11.8% (n = 207) had pre-transplant diabetes, and 13.8% (n = 243) developed PTDM with median time to onset 108 days (IQR 46-549 days). Median follow-up was 1,839 days (IQR 928-2985 days). Disparate management strategies were observed, although insulin was the commonest glucose-lowering therapy for all patients with diabetes. In adjusted models, PTDM was associated with lower mortality (HR 0.663, 95% CI 0.543-0.810) and pre-diabetes with higher mortality (HR 1.675, 95% CI 1.396-2.011). However, if analyses are restricted to those with at least 5-year follow-up, then PTDM has no association with mortality (HR 0.771, 95% CI 0.419-1.096), but pre-transplant diabetes remains associated with higher mortality (HR 2.029, 95% CI 1.367-3.012). CONCLUSIONS: Pre-transplant diabetes remains associated with increased mortality risk after kidney transplantation, but PTDM effects are time dependent. Development of PTDM should be encouraged as a mandated registry return to study the long-term impact on survival outcomes.

HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.

The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear. Methods: In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations. Results: PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001). Conclusion: Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.

Autosomal Dominant Polycystic Kidney Disease Is a Risk Factor for Posttransplantation Diabetes Mellitus: An Updated Systematic Review and Meta-analysis.

Autosomal dominant polycystic kidney disease (ADPKD) is linked with risk for posttransplantation diabetes mellitus (PTDM), but this association has methodologic limitations like diagnostic criteria. The aim of this study was to use contemporary diagnostic criteria for PTDM and explore any risk association for kidney transplant recipients with ADPKD. METHODS: We undertook a retrospective analysis of 1560 nondiabetic kidney transplant recipients between 2007 and 2018 at a single center, of whom 248 (15.9%) had ADPKD. Local/national data were linked for every patient, with manual data capture of PTDM diagnosis by International Consensus Recommendations. We then pooled our data with eligible studies after an updated systematic review and performed a meta-analysis to estimate the pooled effect. RESULTS: Comparing ADPKD versus non-ADPKD kidney transplant recipients, PTDM risk was not significantly different at our center (19.4% versus 14.9%, respectively; P = 0.085). ADPKD patients who developed PTDM were older, borderline heavier, and less likely to be recipients of living kidney donor compared with ADPKD patients who remained free of PTDM. Systematic review of the literature identified 14 eligible studies, of which 8 had a PTDM diagnosis consistent with Consensus recommendations. In the meta-analysis, we observed an increased odds ratio (OR) of kidney transplant recipients with ADPKD developing PTDM regardless of all study inclusion (OR, 1.98; 95% confidence interval, 1.43-2.75) or restricted study inclusion based on robust PTDM diagnostic criteria (OR, 1.81; 95% confidence interval, 1.16-2.83). CONCLUSIONS: ADPKD kidney transplant candidates should be counseled of their increased risk for PTDM, with further work warranted to investigate any underlying metabolic pathophysiology.