Efficacy, Mechanisms and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Summary

In 52 randomized kidney transplant recipients, dapagliflozin increased glucosuria, produced a modest iohexol-measured GFR dip at 1 and 12 weeks, and reduced mean arterial pressure at 1 week without lowering systolic blood pressure. No genitourinary infections occurred, and proximal sodium handling and sympathetic activation were unchanged, suggesting mechanistic heterogeneity versus non-transplant populations.

Key Findings

• Dapagliflozin did not reduce systolic BP but reduced mean arterial pressure at 1 week by 3.9 mmHg (95% CI -7.5, -0.2).
• Placebo-adjusted iohexol-measured GFR decreased by 4.2 and 3.49 ml/min/1.73m2 at 1 and 12 weeks, respectively.
• Increased glucosuria occurred without changes in proximal sodium handling or sympathetic activation; no GU infections were observed.

Clinical Implications

Clinicians can anticipate glucosuria and a modest early GFR dip with dapagliflozin in kidney transplant recipients without increased GU infections; broader efficacy on renal and cardiovascular outcomes requires dedicated trials.

Limitations

• Small sample size and short 12-week duration limit detection of clinical outcome differences
• Primarily mechanistic endpoints; not powered for renal or cardiovascular hard outcomes

Future Directions

Conduct adequately powered outcome trials of SGLT2 inhibitors in kidney transplant recipients to test effects on graft function, cardiovascular events, and survival, and explore mechanisms underlying the observed hemodynamic differences.