Risk of nephrotic syndrome among non-steroidal anti-inflammatory drug users: a population-based study in the United Kingdom

Study type
Protocol
Date of Approval
Study reference ID
17_268
Lay Summary

It is well-known that non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for their anti-inflammatory and painkilling effects can lower kidney function and lead to water and salt retention. Less clear is the role of NSAIDs in the occurrence of nephrotic syndrome (NS). This syndrome is characterized by protein loss in urine, a lower level of proteins in blood and the formation of oedema (fluid accumulation under the skin and around organs). A possible relation between NSAIDs and NS has been suggested in several case reports but a systematic study has not been performed. Therefore, the aim of our study is to evaluate the association between NSAIDs use and the risk of NS in a population-based study. Furthermore, when there is an association, it will be evaluated whether there are patient groups extra vulnerable for this side effect.

Technical Summary

We aim to evaluate the association between NSAIDs and the risk of NS by conducting a case-control study in CPRD. Cases will be patients with a first diagnosis of NS (index-date), while controls will be those without a diagnosis of NS prior to the index-date. Each case will be matched to up to 3 controls by age, sex, practice, and the index-date. Exposure of interest will be NSAID use directly prior or at the index-date. Patients who were not using any NSAIDs prior to the index-date will be categorized as nonusers. Potential confounders taken into account will be comorbidities, co-medications, body mass index (BMI), and lifestyle. The strength of the association between NSAID use and NS will be estimated using conditional logistic regression model with different adjustment models, i.e. 1) no adjustment, 2) adjusted for comorbidities that are known to be associated with NS, 3) additionally adjusted for other potential confounders associated with renal toxicity, and 4) additionally adjusted for BMI and lifestyle factors (full model). Duration of NSAID use in relation to NS will also be studied. Finally, we will assess potential effect modification by age, sex, diabetes mellitus (DM), and membranous glomerulonephritis.

Health Outcomes to be Measured

Nephrotic syndromes

Collaborators

Olaf Klungel - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Anthonius de Boer - Collaborator - Utrecht University
Mohammad Bakhriansyah - Collaborator - Utrecht University

Linkages

HES Admitted Patient Care