Influence of non-steroidal anti-inflammatory drugs on chronic kidney disease progression: an epidemiological study in general practice populations

Abstract

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. Identifying and avoiding disease progression risk factors is important in the management of CKD. Non-Steroidal Anti-inflammatory Drugs (NSAIDs), which are commonly prescribed analgesia, are widely regarded as one risk factor which influences CKD progression. However, the published literature is conflicting and the association between NSAID use and CKD is unclear.

This thesis encompasses a systematic review and a two phase observational study. The systematic review found that high dose NSAID use significantly increased the risk of accelerated CKD progression but normal dose NSAID use did not. However, NSAID doses were unstandardised, the effects of co-morbidity or co-drug therapy were unknown and outcome measures were varied.

The observational phases were performed using linked consultation and prescription general practice data. Subjects aged 40 years and over with at least one estimated Glomerular Filtration Rate (eGFR) measurement (N=7,657) between the 1st/Jan/2009 and 31st/Dec/2010 were included. Cumulative drug prescription (NSAID, aspirin or paracetamol) was standardised using the defined daily dose (DDD) and use categorised into non-user (0 DDD), normal (DDD’s =85th percentile) groups. Phase 1 (cross-sectional study) characterised the CKD population and explored associations between drug prescription and moderate to severe CKD. Phase 2 (cohort design study) investigated the effects of drug prescribing on the development of moderate to severe CKD and significant CKD progression. Multiple logistic regression analyses, adjusting for socio-demographic, co-morbidity and co-drug therapy factors, were used to estimate risk.

Phase 1 findings were that drug prescribing was not significantly associated with moderate to severe CKD. Phase 2 findings were that NSAID or paracetamol prescription did not affect the risk of significant CKD progression. However, high dose aspirin prescribing significantly decreased the risk of significant CKD progression but normal dose aspirin did not.