MO1020: Alkaline Phosphatase to Prevent Ischemia Reperfusion Injury in Living Kidney Transplantation—A Safety Pilot Study

Abstract

Abstract BACKGROUND AND AIMS Ischemia-reperfusion injury (IRI) during kidney transplant procedures can induce acute kidney injury (AKI) [1]. Extracellular ATP is a key player of pro-inflammatory processes during IRI in the kidney [2], whereas conversion of ATP into adenosine has protective effects to the kidney. Alkaline phosphatase (AP) is the only enzyme that converts ATP directly into adenosine by dephosphorylation[3]. In earlier clinical trials of AP in sepsis-associated AKI (SA-AKI), it was suggested that AP has a protective effect on endogenous creatinine clearance and mortality [4]. With the pathophysiologic similarity between SA-AKI and IRI, we aimed to evaluate the effect and feasibility of periprocedural AP to improve kidney function in living donor kidney transplantation. METHOD We conducted a pilot, phase II, double-blinded and randomized controlled trial comparing medicinal AP (tradename: `bRESCAP’, courtesy Alloksys Life Sciences) and placebo. All consecutive recipients of living donor kidneys were asked for informed consent. After randomization, intravenous AP (bolus 1000IU and 9000IU continuously) or placebo was administered at the start of the procedure and continued for the following 24 h. Graft function was measured with measured GFR (using an iohexol distribution curve) after 12 months. Plasma creatinine and a panel of novel injury biomarkers and systemic inflammation markers were measured in both urine and serum during the 7 days after the procedure. Drug reactions and adverse events (AEs) were monitored in the first 7 days. Secondary outcomes included all-cause mortality and dialysis dependency. RESULTS Between June 2019 and October 2019, 11 patients were enrolled. Patients did not differ between groups, bRESCAP (n = 5) and placebo (n = 6) at baseline: 36% were male; the median age was 58 [interquartile range (IQR) 40–65] years; and the median eGFR 12 (10–15) mL/min/1.73 m2. After 1 year, median measured GFR was similar in the bRESCAP group [52.2 (40.5–61.4)] and placebo group [52.4 (37.6–66.1)] (P = 1.000). Mixed model analysis showed no difference in the fall of plasma creatinine or cystatin-C over the first 7 days after the procedure. There were no adverse events observed in the bRESCAP group. CONCLUSION These pilot data indicate that bRESCAP can be administered safely but offers no benefits to recipients of kidneys from living donors. This study opens the way to study recipients of kidneys from deceased donors, where IRI plays a much more prominent role and frequently leads to delayed graft function.