A Randomized Controlled Trial to Evaluate Allopurinol vs Placebo on Left Ventricular Mass in Living Kidney Donors

BACKGROUND: Living kidney donation is regarded safe, though recent studies raise concern on long-term cardiovascular risks, including left ventricular mass and hypertension, resulting in higher cardiovascular mortality. Elevated uric acid has been associated with higher left ventricular mass. We therefore hypothesized that lowering uric acid can reduce left ventricular mass in living kidney donors. METHODS: The study was a single-center, phase 2b efficacy, 1:1 randomized, double-blind, placebo-controlled trial over 9-months. Participants (n=71) were healthy kidney donors aged 18+ with eGFR >30 mL/min/1.73 m2 examined ≥ 6 months after donor nephrectomy. The intervention consisted of allopurinol 300 mg or placebo once daily for 9 months, and the main outcome was change in left ventricular mass from baseline to month 9 in the allopurinol group compared to placebo, evaluated by use of cardiac magnetic resonance imaging (CMR). RESULTS: Uric acid levels were significantly lower in the allopurinol group (p<0.001). We found no significant differences between the changes in MRI-estimated left ventricular mass between the treatment groups. The mean changes were -0.25 (±4.4) g in the allopurinol group and 1.04 (±4.2) g in the placebo group (p=0.25). There was no effect of allopurinol on blood pressure (p=0.98) or indexes of insulin sensitivity (p=0.62). Adverse events occurred in 28 (39%) participants, 18 (70%) in the allopurinol group and 10 (37%) in the placebo group. Three events were considered severe, all in the allopurinol group. CONCLUSIONS: We found no effects on left ventricular mass, blood pressure or insulin sensitivity of nine months of allopurinol treatment in living kidney donors, despite a significant effect on uric acid.