KEY POINTS:
- Ouabain, a cardiac glycoside that is structurally similar to digoxin, has been shown to impair renal function in animal models. This finding suggests that Digifab, which binds to ouabain receptors, may help prevent AKI
- Digifab, an antidote for digoxin toxicity, was associated with a lower incidence of AKI in patients with high levels of endogenous ouabain undergoing CABG, but did not significantly impact eGFR
Investigators aimed to determine whether Digifab reduces the risk of acute kidney injury (AKI), a common and serious complication, in patients undergoing coronary artery bypass grafting (CABG).
Endogenous ouabain (EO), a cardiac glycoside that is structurally similar to digoxin, is elevated in patients with hypertension and demonstrated to cause decreased renal function in mice models. Digifab, an antidote for digoxin toxicity, binds to ouabain receptors with high affinity, preventing ouabain from activating them.
In this double-blind, placebo-controlled pilot trial, 250 patients undergoing CABG with high AKI risk, defined by an Hgb A1c ≥ 6.5% or estimated glomerular filtration rate (eGFR) <60, were randomized in a 1:1 fashion to receive 80mg Digifab or placebo 12-15 hours before surgery and again at the time of surgery. Patients with AKI before CABG, kidney transplant, eGFR < 15, or who had received contrast within 36 hours were excluded.
The primary outcome was a change in eGFR in patients with EO levels above population median (high EO), assessed three-days post-CABG. There was no significant change in eGFR in patients with high EO between the Digifab or placebo group with a median eGFR change of 2.08 [-5.10, 9.82] in the Digifab group and median eGFR change of 1.59 [-7.93, 8.31] in the placebo group.
Secondary outcomes included incidence of AKI, defined as serum creatinine increase of 0.3mg/dl or 150% of baseline and markers of renal injury (NGAL, KIM1).
The incidence of AKI was lower in the Digifab group with 5 of 59 patients (8.5%) affected, compared to 12 of 66 patients (18.2%) in the placebo group. Among patients with high EO, after adjusting for baseline eGFR, Digifab administration was associated with a lower rate of AKI (OR 0.274, 95 % CI [0.073-0883], p=0.039).
Pre-operative Digifab reduced the incidence of acute kidney injury in CABG patients with high preoperative EO but did not affect eGFR or markers of renal damage. Larger studies are needed to evaluate the benefit of Digifab in preventing kidney injury.