C1-inhibitor may help prevent contrast-induced nephropathy

Given before coronary angiography in high-risk patients, recombinant human C1-esterase-inhibitor (rhC1INH) reduces biomarkers for contrast-induced kidney injury, reports a trial in JACC: Cardiovscular Interventions.

The Prophylactic RhC1-inhibitor to Prevent Contrast-induced Nephropathy (PROTECT) trial included 77 high-risk patients scheduled for elective coronary angiography. All had an eGFR of ≤50 mL/min per 1.73 m2 plus one additional risk factor (diabetes, age ≥75, anemia, congestive heart failure, or history of pulmonary edema). The patients were 54 men and 23 women, mean age 77 years and mean eGFR 40 mL/min per 1.73 m2.

Patients were randomly assigned to treatment with rhC1INH 50 IU/kg or placebo before and 1 hour after coronary angiography. The main efficacy outcome was peak change in neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of kidney injury. Secondary outcomes included contrast-induced nephropathy (CIN), based on serum creatinine increase of at least 25% or 0.5 mg/dL, and a ≥10% increase in cystatin C.

On per-protocol analysis, rhC1INH was associated with a lower peak change in NGAL: 4.7 ng/mL versus 22.5 ng/mL. However, a modified intention-to-treat analysis found no significant difference: 7.2 ng/mL versus 22.5 ng/mL, respectively.

On a post hoc analysis of patients undergoing percutaneous coronary intervention, the peak change in NGAL was sharply lower in the rhC1INH group: median 1.8 ng/mL versus 26.2 ng/mL.

Sixteen percent of patients receiving rhC1INH had a cystatin C increase of ≥10% within 24 hours, compared with 33% of the placebo group. The CIN rate was similar between groups: 10.5% and 5.6%, respectively. Adverse events were comparable as well.

New approaches are needed to prevent contrast-associated kidney injury in high-risk patients. rhC1INH, which is approved for the treatment of hereditary angioedema, has been shown to reduce renal ischemia/reperfusion injury in animal models.

This proof-of-concept study reports reductions in NGAL and cystatin C in high-risk patients receiving rhC1INH before elective coronary angiography. The protective effect appears larger in patients undergoing percutaneous coronary interventions.

The authors call for larger clinical trials of rhC1INH for this indication, addressing CIN rate and other meaningful clinical outcomes [Panagiotou A, et al. A randomized trial of recombinant human C1-esterase-inhibitor in the prevention of contrast-induced kidney injury. JACC: Cardiovasc Interv 2020; 13:833–842].

June 2020 (Vol. 12, Number 6)