Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury

Abstract

Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m, incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy.

Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRD

“…45,46 Details on the VA datasets used are provided in Supplemental Material. [47][48][49][50][51] Data from the US Renal Database System (USRDS) was used to supplement ESRD status information. The Center for Disease Control's (CDC) National Environmental Public Health Tracking Network furnished annual particulate matter estimates for the contiguous United States that originate from Community Multiscale Air Quality modeled output.…”

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial

“…Mediation analyses were also utilized to evaluate the proportion of the total effect on the primary outcome and death from any cause associated with AKI. Accelerated failure time models with Weibull distributions for time to the outcomes were used and logistic regression was utilized for AKI as the mediator [21]. Models used for mediation analysis were also estimated and included baseline clinical risk factors as co-variates (age, sex, race, systolic blood pressure, BMI, number of antihypertensive medications, clinical cardiovascular disease and CKD status).…”

A big data approach to examine the association of high density lipoprotein cholesterol and mortality: lessons for future investigations

“…A big data approach might provide further insight and offer significant value that should be realized through innovative research endeavors to challenge prior assumptions, and fill important and consequential knowledge gaps (11)(12)(13). We predict that the pursuit of big data research will very likely upend several long-held assumptions, and as a result will enrich our understanding of health and disease and favorably impact the human condition.…”