Renal transplantation is the most effective and cost-efficient form of renal replacement therapy for a burgeoning population that presents with end-stage renal disease. Although organ donation has become a national priority, the gap between the number of patients awaiting a kidney vs. the number of available kidneys continues to widen exponentially. In many countries within the European Union, utilization of "donation after cardiac death" (DCD) kidneys is steadily increasing, expanding the donor pool by >50%. Given the high incidence of cardiac deaths in this country, aggressive pursuit of the DCD kidney pool could potentially reduce waitlist periods to months, if not days. Risk for delayed graft function (DGF) with the attendant risks for increased recipient morbidity, chronic allograft nephropathy and increased medical costs has however tempered DCD kidney utilization in this country. Development of strategies that limit normothermic reperfusion injury, promote renal repair, reduce the incidence and/or duration of DGF and improve long-term outcome can greatly enhance acceptance and recruitment of DCD kidneys. Angion Biomedica is developing BB3, a small molecule hepatocyte growth factor mimetic that exhibits significant tissue protective activity in numerous models of acute renal injury. Importantly, this small molecule has completed clinical safety trials in both healthy volunteers and in patients with renal impairment. The present proposal is a pilot evaluation of safety and efficacy of intravenously administered BB3 in recipients of kidneys from DCD donors who are risk for developing DGF. This trial, to be conducted at Maastricht University Medical Center in the Netherlands, is unique in that it compares drug vs. placebo outcome in kidney recipients from the same donor with direct evaluation of function (creatinine clearance) in the graft. Results from this pilot study will form the basis of conducting a large multi-center Phase III trial evaluating efficacy and safety of BB3 in DCD kidney recipients at risk for DGF. Successful completion of these trials will more than likely change the kidney donor recruitment landscape here in the US.
The proposed study has significant clinical ramifications. A small molecule that improves post-transplantation function and outcome in higher risk donor kidneys can potentially increase the donor pool thereby reducing significantly the number of deaths in patients awaiting kidney transplant.