Metabolic and macrovascular outcomes following simultaneous pancreas–kidney transplantation and kidney transplantation alone in recipients with type 1 diabetes mellitus: a systematic review and meta-analysis

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Abstract Aims/hypothesis Simultaneous pancreas–kidney transplantation (SPKTx) and kidney transplantation alone (KTx) are common treatment modalities for individuals with type 1 diabetes with end-stage kidney disease. This study compared metabolic and macrovascular disease outcomes between SPKTx and KTx in recipients with type 1 diabetes. Methods We conducted a systematic search of the Embase, MEDLINE and Scopus databases (last searched 23 February 2025). We included retrospective and case–control studies, owing to a lack of randomised controlled trials in English, with adult patients. We excluded studies reporting on a return to dialysis post transplant, islet–kidney transplantation or separate pancreas–kidney transplants. Bias and study quality were assessed via the Newcastle–Ottawa scale for cohort studies. Demographic and outcome data were synthesised as both categorical and continuous data, with pooled means and summary statistics computed where applicable. Meta-analysis was performed on post-transplant outcomes in studies evaluating total cholesterol (TC), triglyceride (TG) level, HDL, LDL, blood pressure, HbA 1c and renal function. Macrovascular outcomes included the frequency of new or adverse events associated with coronary artery disease (CAD), cerebrovascular disease (CeVD) and peripheral vascular disease (PVD). Results A total of 15 studies ( n =564 SPKTx, 419 KTx) were included. Meta-analysis demonstrated lower post-transplant TC (mean difference −0.41 mmol/l [95% CI −0.60, −0.22], p <0.01, I 2 =37%), TG level (mean difference −0.76 mmol/l [95% CI −1.02, −0.49], p <0.01, I 2 =86%), LDL (mean difference −0.28 mmol/l [95% CI −0.42, −0.14], p <0.01, I 2 =15%), HbA 1c (mean difference −28.79 mmol/mol [95% CI −35.75, −21.82], p <0.01, I 2 =98%; mean difference −2.61% [95% CI −3.05, −2.16], p <0.01) and creatinine levels (mean difference −21.54 μmol/l [95% CI −39.23, −3.85], p =0.02, I 2 =90%) following SPKTx compared with KTx. Mean antihypertensive agent use per participant decreased post SPKTx (1.0 vs 2.5 pre transplant; p <0.01), but was not significantly different from post-KTx groups. HbA 1c increased following KTx (69 mmol/mol [8.5%]) compared with pre KTx (53 mmol/mol [7.0%], p <0.01). Progression of CAD, CeVD and PVD occurred across both groups post transplant. PVD showed more than a twofold increase in amputations and revascularisations post transplant. No difference was observed in the post-transplant frequency of CAD, CeVD or PVD between SPKTx and KTx. Evidence from this study was limited by a lack of subgroup data for analysis, a lack of randomised studies and a paucity of reported lifestyle factors influencing outcomes. Conclusions/interpretation SPKTx demonstrates a superior metabolic profile post transplant to that in KTx in recipients with type 1 diabetes. However, this does not translate into differences in the risk of CAD or PVD post transplant, with PVD accounting for the greatest burden of macrovascular disease. Registration This protocol has been registered a priori on PROSPERO (CRD42024622408).

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