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

Abstract

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.

Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease

“…An individualized approach to timing and need for nephrectomy based on patient's needs, preference, and surgical risk, would likely be the most optimal clinical practice 48 . Some studies 11,15,49,50 and meta-analyses 51,52 have showed increased risk of PTDM in PKD recipients, but this has not been a consistent finding 53,54 and most of these studies have small number of PKD patients. Amongst the 2 largest cohorts, however, one study has minimally increased risk of PTDM with PKD in an unadjusted analysis 15 while the other has none 54 In conclusion, renal allograft and patient survival is better in PKD than in other native kidney diseases post-kidney transplant.…”

Obesity and Post-Transplant Diabetes Mellitus in Kidney Transplantation

“…Finally, increased odds of developing PTDM among kidney transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) have also been described [ 53 ], potentially related to polycystin-1 and polycystin-2 expression in organs outside of the kidney, such as the pancreas [ 54 ].…”

“…A large retrospective study of more than 25,000 transplant recipients showed that steroid-free immunosuppression was associated with a lower risk of PTDM occurrence compared to steroid-containing therapy. The cumulative incidence of PTDM within 3 years of transplantation was 12.3% and 17.7% for steroid-free therapy and steroid-containing therapy, respectively [ 53 ]. However, in a recent double-blind 5-year study comparing a group of patients who initially stopped corticosteroids with a group who reduced corticosteroids to 5 mg/day after 6 months, there was no difference seen in the rate of PTDM (35.9% in the group that discontinued corticosteroids, and 36.3% in the group that maintained 5 mg per day after 6 months) [ 56 ].…”

Global Epidemiology, Health Outcomes, and Treatment Options for Patients With Type 2 Diabetes and Kidney Failure

“…The mechanistic pathway for this association remains unclear but may be related to the direct viral-induced toxic effect on beta cells, induction of insulin resistance secondary to hepatic steatosis, and/or excess production of pro-inflammatory cytokines (83)(84)(85)(86)(87)(88)(89). Other less recognized risk factors for PTDM include the presence of autosomal dominant polycystic kidney disease and pre-and post-transplant hypomagnesemia, but these associations remain inconsistent and may be related to the residual effects of post-transplant confounding factors (90)(91)(92)(93)(94)(95). The failure of magnesium supplementation to improve insulin resistance and glucose metabolism in two small, randomized trials in kidney transplant recipients has challenged the potential causal relationship between hypomagnesemia and the development of PTDM (96,97).…”