Microalbuminuria in heart transplant recipients -insights from the randomized trial dapagliflozin for renal protection in heart transplant recipients (DAPARHT)

Background Heart transplantation is the preferred treatment for a selected group of patients with end-stage heart failure, but kidney function often declines after heart transplantation. Microalbuminuria is an early indicator of kidney dysfunction. It is defined as a urinary albumin/creatinine ratio (UACR) >3.0 mg/mmol and ≤30 mg/mmol. Sodium glucose transporter 2 inhibitors (SGLT2i) protect against kidney failure in patients with kidney disease or diabetes, particularly in those with microalbuminuria. However, the association between glomerular filtration rate and microalbuminuria in heart transplant recipients is not well known. In the randomized DAPAgliflozin for Renal protection in Heart Transplant Recipients (DAPARHT) trial, we assess the effect of the SGLT2i dapagliflozin on kidney function. Purpose The purpose of this abstract is to present baseline microalbuminuria in the first 300 heart transplant recipients enrolled in the DAPARHT trial, and to assess to what extent microalbuminuria is associated with the eGFR in this population. Methods DAPARHT is an investigator-initiated, double-blind, placebo-controlled, international trial designed to randomize 430 heart transplant recipients in a 1:1 ratio to receive either 10 mg/day of the SGLT2i dapagliflozin or matching placebo. Participants are enrolled at least one year after transplantation. Exclusion criteria include an estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73m², and type 1 diabetes. The primary endpoint is the difference in the slope of eGFR from two weeks to 12 months. A secondary endpoint is the change in UACR from baseline to end-of-treatment. The UACR is measured in spot urine. Results Enrollment began in June 2022 in Norway, October 2023 in the Netherlands, and October 2024 in Sweden. The final patient visit is scheduled for May 2028. Of the first 300 patients enrolled, UACR data were available for 227 participants. The median baseline UACR was 1.2 mg/mmol [0.5 – 4.0]. At baseline, 29% of participants had a UACR > 3 mg/mmol, and 5% had a UACR > 30 mg/mmol. The mean baseline eGFR was 66 ± 22 mL/min/1.73m². The correlation coefficient between log_UACR and eGFR was -0,21 (p=0,02). 14 % of patients with microalbuminuria also had an eGFR < 60 ml/min/1.73 m2. Conclusion Almost 30 % of the heart transplant recipients participating in the DAPARHT trial had microalbuminuria. UACR correlated weakly with eGFR. The DAPARHT trial will provide information on the effect of dapagliflozin on microalbuminuria in heart transplant recipients, and whether a reduction in albuminuria is associated with improved kidney outcomes.