Association of diuretic use with increased risk for long-term post-transplantation diabetes mellitus in kidney transplant recipients

Nephrol Dial Transplant. 2022 Jun 23;37(7):1375-1383. doi: 10.1093/ndt/gfac012.

Abstract

Background: Post-transplantation diabetes mellitus (PTDM) is a major clinical problem in kidney transplant recipients (KTRs). Diuretic-induced hyperglycaemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in KTRs.

Methods: We included 486 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Participants were classified as diuretic users and non-users based on their medication use verified by medical records.

Results: At the baseline study, 168 (35%) KTRs used a diuretic (thiazide, n = 74; loop diuretic, n = 76; others, n = 18) and 318 KTRs did not use a diuretic. After 5.2 years [interquartile range (IQR) 4.0‒5.9] of follow up, 54 (11%) KTRs developed PTDM. In Cox regression analyses, diuretic use was associated with incident PTDM, independent of age, sex, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) {hazard ratio [HR] 3.28 [95% confidence interval (CI) 1.84-5.83]; P <0.001}. Further adjustment for potential confounders, including lifestyle, family history of cardiovascular disease, use of other medication, kidney function, transplantation-specific parameters, BMI, lipids and blood pressure did not materially change the association. Moreover, in Cox regression analyses, both thiazide and loop diuretics associated with the development of PTDM, independent of age, sex, FPG and HbA1c [HR 2.70 (95% CI 1.24-5.29); P = 0.012 and HR 5.08 (95% CI 2.49-10.34); P <0.001), respectively].

Conclusions: This study demonstrates that diuretics overall are associated with an increased risk of developing PTDM in KTRs, independent of established risk factors for PTDM development. The association was present for both thiazide and loop diuretics.

Keywords: diuretics; kidney transplant recipients; loop diuretics; post-transplantation diabetes mellitus; thiazide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus* / epidemiology
  • Diabetes Mellitus* / etiology
  • Diuretics / adverse effects
  • Glycated Hemoglobin / analysis
  • Humans
  • Kidney Transplantation* / adverse effects
  • Postoperative Complications / epidemiology
  • Postoperative Complications / etiology
  • Prospective Studies
  • Risk Factors
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Thiazides
  • Transplant Recipients

Substances

  • Diuretics
  • Glycated Hemoglobin A
  • Sodium Potassium Chloride Symporter Inhibitors
  • Thiazides