Proton Pump Inhibitor Use and Progression to Major Adverse Renal Events: A Competing Risk Analysis.
QJM. 2019 Jun 28. Epub 2019 Jun 28. PMID: 31251364
Christopher H Grant
BACKGROUND: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD).
AIM: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD.
DESIGN: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 01/01/2006 until 31/12/2016.
METHODS: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis.
RESULTS: There were 3,824 patients with CKD included in the analyses of whom 1,195 were prescribed a PPI. The PPI group was younger (64.8 vs 67.0 years, p < 0.001), with lower eGFR (30 vs 35 ml/min, p < 0.001) and more proteinuria (64 vs 48 mg/mmol, p < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (HR 1.13 [95% CI 1.02-1.25], p = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs 18.9%, p < 0.001).
CONCLUSION: PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings.