Diuretic use following kidney transplant significantly increases the risk of patients developing diabetes, potentially leading to serious complications including graft loss, one of the first studies to evaluate the use of diuretics in renal transplant recipients indicates.
"Post-transplantation diabetes mellitus (PTDM) can cause a lot of complications for renal transplant recipients as they are very vulnerable patients, and the treatment of diabetes is also very challenging because of patients' insufficient renal function," researcher Sara Oskooei, MD, PhD candidate, University Medical Center, Groningen, The Netherlands, told Medscape Medical News.
"So I think as nephrologists we need to develop some risk models for post-transplant diabetes and categorize our renal transplant recipients into high versus lower risk for diabetes, and then personalize our approach to their treatment, where low-risk patients may still benefit from diuretic use but patients at high risk for diabetes would not," she added.
Oskooei presented her findings during the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 2021 annual meeting.
Asked by Medscape Medical News to comment on the findings, Jeffrey Schiff, MD, assistant professor of medicine, University of Toronto, Ontario, Canada, acknowledged that post-transplant diabetes is an important issue.
"We know that patients who develop post-transplant diabetes are at higher risk for graft loss and death, so preventing it is an important goal," he said in an email. Schiff also noted that the thiazide diuretics have long been associated with a higher incidence of diabetes in the general population than other antihypertensive drug classes, "so this finding amongst a cohort of transplant recipients is not surprising," he observed.
What was surprising, however, was to see the same effect in patients taking a loop diuretic, who in fact had an even higher incidence of post-transplant diabetes. "If confirmed, this would mean that loop diuretics affect glucose metabolism differently in renal transplant recipients compared to the general population," Schiff suggested.
Diabetes in Diuretic vs Nondiuretic Users
For the study, 486 patients at least 1 year out from transplantation were enrolled. "Participants were classified as diuretic users and nondiuretic users based on their medication use recording at baseline," the authors note. A total of 318 participants were nondiuretic users and 168 participants, or 35% of the overall cohort, had been prescribed a diuretic.
At a mean follow-up of 5.4 years, 11% of kidney transplant recipients had developed post-transplant diabetes. However, the incidence of post-transplant diabetes was significantly higher, at 18%, in diuretic users compared with 7% in the nondiuretic users (P < .001), as Oskooei reported.
Further exploratory analysis suggested that thiazides and loop diuretics — the two main types of diuretics used for renal transplant recipients — were associated with an increased risk of post-transplant diabetes, but the incidence was higher with loop diuretics, at 22%, than thiazides, at 13% (P < .001).
"This association remained independent of further adjustment for potential confounders including lifestyle, use of other medication, kidney function, transplantation-specific parameters, body mass index, lipids, and blood pressure," the investigators note.
Oskooei and colleagues also identified multiple different diuretic metabolites in the urine of the sample cohort, "and results were similar to our primary analysis for diuretic use and also for thiazide and loop diuretics, which confirm our primary results," she noted, adding, "ours is one of the first studies evaluating the use of diuretics in renal transplant recipients."
"But since diuretics are sometimes important for the treatment of these patients, we need to find risk models and apply them to the individual treatment of each patient," she reaffirmed.
Weigh Risks and Benefits of All Medications After Kidney Transplant
Schiff said the finding of a greater risk of diabetes after transplant with loop diuretics compared with thiazides may have occurred by chance "due to the relatively small size of the study, so it needs to be confirmed by larger studies," he noted.
In the meantime, given that many transplant recipients do require diuretics as part of their medication regimen, transplant nephrologists need to carefully assess the risks and benefits of all medications they prescribe to any patient in order to promote the best outcomes with the least side effects, he advised.
Commenting further on the study, Matthew Weir, MD, London Health Sciences Centre, London, Ontario, agreed with Schiff that diabetes arising after kidney transplantation is an important although under-studied topic.
"The authors should be congratulated for their work in this area, and their study findings are thought-provoking," he said in an email.
However, Weir, too, feels more work is needed to clarify the risk posed by diuretics and to frame that risk for patients requiring treatment.
"The volume-overloaded state diuretics are prescribed for is far from benign and may more than balance out the risk of drug-induced diabetes," Weir emphasized.
The relationship between diuretics, other transplant medications, graft function, and diabetes — which can be fraught with confounders — needs to be explored in follow-up studies, he concluded.
The study was funded by the European Union Horizon 2020. Oskooei has reported no conflicts of interest. Schiff has reported serving on an advisory board for Novartis within the past year.
ERA-EDTA Virtual Congress. Abstract MO 146. Presented June 7, 2021.
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