Blog entry by Meguid El Nahas

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by Meguid El Nahas - Monday, 9 May 2016, 6:44 AM
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J Am Soc Nephrol. 2016 Apr 14. pii: ASN.2015121377. [Epub ahead of print]

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.


The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure toPPI associates with incident CKDCKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2blockers;n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKDCKD progression, and ESRD.


PPI have been over prescribed and over used in the last 2 decades...

Whilst we all came across many cases of AIN due to PPIs, new concern about incident and progressive CKD linked to PPIs is being raised (see above).

This is difficult to ascertain in terms of causality as these associations are often biased and confounded by analgesics and CKD...those with underlying medical problems, comorbidities, consume them...then of course those same individuals are at increased risk of CKD...and ESRD! Also, those with ischemic heart disease and atherosclerotic renal ischemia are often given anti-platelet agents and...PPIs prophylactically...

Of interest, a similar association has been put forward between PPIs and CVD, adverse cardiac events,

...the same logic of "confounded by indication" may underly such association; those with CVD are often are on anti-platelt agents and...PPIs prophylactically?!

However, the use of PPIs in renal transplant recipients, in association with steroids, has been linked to osteoporosis and fractures... in fact, there are 34 studies in almost 2 million participants that have reported an association between PPIs and risk of fracture... again, this association doesnt prove causality as older patients are prescribed PPIs more than younger individuals...and the former also tend to be more prone to falls and fractures...

PPIs are more expensive than H2-blockers and tend to be for life...with rebound acidity making rapid withdrawal quite difficult...

So, should we still prescribe them...with doubts over their association with CVD, MBD, CKD progression and ESRD... or is it time to ditch them?!

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