Proton Pump Inhibitors Are Not Associated With Acute Kidney Injury in Critical Illness

Abstract

Recent epidemiologic data linking proton pump inhibitor (PPI) use to acute and chronic kidney dysfunction is yet to be validated in other populations, and mechanisms have not been explored. Using a large, well phenotyped inception cohort of 15,063 critically ill patients, we examined the risk of acute kidney injury (AKI), as defined by the Kidney Disease Improving Global Outcomes criteria guidelines, according to prior use of a PPI, histamine-2 receptor antagonist (H2RA), or neither. A total of 3,725(24.7%) patients reported PPI use prior to admission, while 905(6.0%) patients reported H2RA use. AKI occurred in 747(20.0%) and 163(18.0%) of PPI and H2RA users respectively, compared to 1,712(16.2%) of those not taking acid suppressive medications. In unadjusted analysis, PPI and H2RA users had a 28% (95% CI 1.17–1.41, p<0.001) and 10% (95% CI 0.91–1.30, p=0.31) higher risk of AKI compared to those taking neither class of medication. However, in sequential models that included adjustment for demographics, cardiovascular comorbidities, indications for PPI use, and severity of illness, the effect of PPI on the risk of AKI was attenuated, and in the adjusted analysis, PPI was not associated with AKI (OR 1.02; 95% CI 0.91–1.13, p=0.73). The presence of sterile pyuria and hypomagnesemia did not modify the association between PPI use and AKI. In summary, after adjustment for demographics, illness severity and the indication for PPI use, PPI use prior to admission is not associated with critical illness AKI.

Acid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis

“…All studies adjusted the risk estimate for gender and age at least. OR and HR were used to estimate the risk of KD by six studies and four studies, respectively (Tables S1,S2). …”

“…Of these, 503 references and 12 references were excluded after title/abstract screening and full-text review, respectively. Eventually, 10 studies out of nine 11,12,[24][25][26][27][28][29][30] articles were included in our meta-analyses ( Fig. 1).…”

“…Antoniou et al . found that PPI significantly increased the risk of acute kidney injury (AKI) in elderly patients, whereas Lee et al . did not observe such significant association in patients with critical illness.…”

“…6,7 Recently, more concerns have been raised for proton pump inhibitors (PPIs) about the related risks of acute interstitial nephritis (AIN), chronic kidney disease (CKD), and even end-stage renal disease (ESRD). [8][9][10] Antoniou et al 11 found that PPI significantly increased the risk of acute kidney injury (AKI) in elderly patients, whereas Lee et al 12 did not observe such significant association in patients with critical illness. Besides PPIs, another commonly used acid-suppressive drugs (ASDs), histamine 2 receptor antagonist (H 2 RA), has been reported similar adverse kidney effects, such as interstitial nephritis and acute renal failure.…”

Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies

“…Several case–control and cohort studies explored the association between exposure to PPIs and AKI, but the outcomes remained inconsistent 11–16. Five studies demonstrated that PPIs use was significantly associated with increased risk of AKI,12–14,16 whereas no obvious relevance was found in other studies 11,15…”