P-CABs Linked With Lower Risk for Kidney Decline Than PPIs

Proton pump inhibitors (PPIs) are known to increase the risk for acute kidney injury and incident chronic kidney disease (CKD). Potassium-competitive acid blockers (P-CABs) have emerged as a potentially safer alternative, but their impact on kidney health is still unclear. Researchers in South Korea, led by Minyoung Jang, PhD, conducted a retrospective observational study designed to compare renal outcomes of P-CABs with those of PPIs.

The study was conducted from January 2019 to May 2023 at a tertiary referral hospital in Seoul, South Korea. Eligible participants were aged 18 years or older and were prescribed a once-daily oral PPI (esomeprazole 40 mg) or P-CAB (tegoprazan 50 mg) during hospitalization or outpatient visits.

Renal outcomes of interest were doubling of creatinine levels and a 50% or greater decline in estimated glomerular filtration rate (eGFR). Censoring events included the end of follow-up, loss to follow-up, death, or transfer to another facility. The researchers used Cox proportional hazard analyses to adjust for multiple covariates.

The overall cohort comprised 6,941 participants (P-CAB: n=1,820; PPI: n=5,121). During a median follow-up of 447 days, patients underwent a median of five creatinine measurements. The two groups were similar in baseline demographic characteristics, except the P-CAB group was slightly older and included fewer males. Diabetes and hypertension were more common in the P-CAB group. Prescription of the study drug duration was comparable between the two groups.

The incidence rates per 1,000 person-years of creatinine doubling were lower in the P-CAB group than in the PPI group (13.4 vs 36.5, respectively; log-rank, P<0.001). Incidence rates of decline in eGFR of 50% or greater were also lower in the P-CAB group compared with the PPI group (18.4 vs 39, respectively; log-rank, P<0.001).

Univariate analysis showed a lower risk for both creatinine doubling and eGFR decline with P-CBA compared with PPI (hazard ratio [HR], 0.42; 95% CI, 0.30-0.59; P<0.001 and HR, 0.50; 95% CI, 0.37-0.69; P<0.001, respectively). Following adjustment for multiple covariates, hazard ratios for creatinine doubling and eGFR decline with P-CAB were 0.52 (95% CI, 0.37-0.74; P<0.001) and 0.63 (95% CI, 0.46-0.87; P=0.005).

The researchers cited several limitations to the study findings, including the possibility of residual confounding due to the single-center retrospective design, likely overrepresentation of patients at higher risk for renal dysfunction, and a lack of data on some clinically relevant factors.

In conclusion, the authors wrote, “Our study suggests that P-CABs may be a relatively safer alternative in terms of renal function for patients at risk of CKD progression who require long-term PPI use.” However, they noted that further prospective studies with long-term follow-up and larger cohorts are required to validate and supplement the findings.