Acute kidney injury (AKI) is a major complication of cardiac surgery and can progress to chronic kidney disease and death. AKI rates in cardiac surgery have been increasing, and treatment strategies are needed since post-AKI recovery of kidney function is associated with improved survival. Allogeneic mesenchymal stem cells (MSCs) have been shown to reduce the severity of and improve the recovery from AKI in preclinical studies.

Madhav Swaminathan, MD, Duke University Health System, Durham, North Carolina, USA, discussed A Study to Evaluate the Safety and Efficacy of AC607 for the Treatment of Kidney Injury in Cardiac Surgery Subjects [NCT01602328]. The objective of this phase 2 randomized double-blind study was to compare the time to kidney recovery (TKR) with AC607 (human MSCs that have been isolated and expanded, then administered via catheter in the groin) vs placebo in the setting of postcardiac surgery.

The study included patients who were undergoing cardiac surgery, including cardiopulmonary bypass (CPB) surgery, with a baseline creatinine within 30 days of surgery. Postoperative AKI was defined as a ≥ 0.5-mg/dL rise in serum creatinine from baseline within 48 hours after CPB. The primary end point was TKR (creatinine return to preoperative baseline). The secondary end point was all-cause mortality or dialysis at 30 or 90 days. Exploratory end points included length of stay, intensive care unit stay, and in-hospital mortality.

Of 26 548 patients tracked, 1990 were eligible, and 156 patients were randomly assigned to AC607 (2 × 10⁶ human MSCs per kg; n = 77) or placebo (n = 79). Equal numbers in each group completed 30 (n = 60) and 90 days (n = 57) of follow-up. Patients were well matched for baseline characteristics, including age, sex, and baseline renal function.

There was no difference between treatment groups for any of the following parameters: median TKR (15 days- treatment vs 12 days-placebo), TKR for patients whose CPB time was > 120 minutes, TKR recovery by CPB time quartiles, or TKR by timing of dosing (< 24, > 24 to 36, or > 36 hours).

All-cause mortality or dialysis at day 30 for AC607 vs placebo was 11 vs 8, respectively; at day 90, it was 12 vs 9. All-cause mortality for AC607 vs placebo at day 30 was 6 vs 5, respectively; at day 90 it was 8 vs 6. In-hospital mortality for AC607 vs placebo was 7 vs 4 days, respectively; dialysis at day 30 for AC607 vs placebo was 7 vs 5; and median hospital length of stay for AC607 vs placebo was 14 vs 12 days. There was no statistical difference between treatment groups for any of these events.

Although AC607 appears safe and well tolerated in postcardiac surgery patients with AKI, it did not reduce the TKR compared with placebo. The low event rates make it difficult to observe a treatment effect without a large study population—but a large study would require investigators to screen a prohibitive number of patients for randomization.