Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury.
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/1.73m2 (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/1.73m2, 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.
['Xie|Yan|Y|', 'Bowe|Benjamin|B|', 'Li|Tingting|T|', 'Xian|Hong|H|', 'Yan|Yan|Y|', 'Al-Aly|Ziyad|Z|']
D058186:Acute Kidney Injury D000328:Adult D000368:Aged D015897:Comorbidity D016208:Databases, Factual D018450:Disease Progression D004334:Drug Administration Schedule D005260:Female D005919:Glomerular Filtration Rate D006635:Histamine H2 Antagonists D006801:Humans D015994:Incidence D007668:Kidney D007676:Kidney Failure, Chronic D008297:Male D008875:Middle Aged D011379:Prognosis D054328:Proton Pump Inhibitors D012307:Risk Factors D013997:Time Factors D014481:United States D014493:United States Department of Veterans Affairs
acute kidney injury chronic kidney disease clinical nephrology