Background. 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.
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 followup 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.
Background. 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,; 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.
Background and Aims Counselling kidney transplant candidates for their personalised risk of developing post-transplantation diabetes mellitus (PTDM) requires an understanding of risk factors. While some risk factors are well defined (e.g. age, ethnicity, body mass index), others like HLA typing are heterogeneously reported and lack consistency. The aim of this study was to investigate the association between HLA alleles and PTDM risk. Method Data was retrospectively extracted from hospital informatics systems for all kidney transplant recipients at a single-centre between 2007 and 2018, with patients excluded if they had pre-existing diabetes. Electronic patient records were then manually searched and records linked to various sources (e.g. NHS Blood and Transplant tissue typing, Hospital Episode Statistics, national death registry) to create a well-phenotyped cohort. Standard immunosuppression for all kidney transplant recipients during this study period was basiliximab induction with maintenance immunosuppression consisting tacrolimus, mycophenolate mofetil and low-dose corticosteroids. PTDM classification was aligned with International Consensus recommendations. Results Data was extracted for 1,560 kidney allograft recipients, with median follow up 5.4 years (IQR 2.7-8.7 years) up to October 2018. PTDM developed in 243 kidney transplant recipients (incidence 15.6%). A range of HLA alleles were examined (e.g. HLA-A, HLA-B, HLA-Cw, HLA-Bw, HLA-DR and HLA-DQ) but only the presence of HLA-Cw12 allele was associated with risk for PTDM (27.4% versus 14.3%, p<0.001) along with a selection of predominately recipient- and transplant related variables. In a logistic regression model, adjusted for all variables with a p-value <0.15 on univariate analysis, recipient HLA-Cw12 was found to be an independent risk factor associated with development of PTDM (Odds Ratio 1.793 [95% confidence interval 1.070-3.002], p=0.027) along with recipient female sex, recipient age, recipient BMI and recipient non-white ethnicity. Conclusion HLA-Cw12 allele in the kidney transplant recipient is independently associated with development of PTDM, although it is important to acknowledge association does not imply causality. This association has not been previously reported and requires validation and further investigation to understand any possible underlying biological mechanisms.
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