Non-steroidal anti-inflammatory drugs and risk of kidney cancer: A Swedish nationwide cohort study in the general and high-use populations

Background. Data on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and kidney cancer (KC) are conflicting. This study aimed to evaluate this association in the general population and in patients with extensive NSAID use: rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods. We conducted a nationwide register-based cohort study of the Swedish general population and among patients with RA or SpA, among whom NSAID use was around five times higher. In each of these cohorts, we assessed the incidence of KC 2010 through 2021 by NSAID exposure as defined by repeated prescriptions. We also evaluated KC mortality in individuals treated (vs. not) with NSAIDs, taking the cancer stage into account. Adjusted hazard ratios (HRs) were calculated through Cox regression, taking age, sex, educational level, comorbidities and family history of KC into account. Results. Based on 751 incident cases of KC among 393,709 individuals in the general population (33% NSAID-exposed), the HR for NSAID-exposure was 1.32 (95% confidence interval [CI] 1.13-1.54), with the highest HRs during the first year of follow-up (HR thereafter 1.20). The corresponding cancer stage-adjusted HR for mortality from KC with NSAID-exposure was 1.26 (95%CI 0.87-1.82). In RA and SpA, the HRs for KC incidence with NSAID exposure were 0.83 (95%CI 0.58-1.18) and 1.60 (95%CI 0.78-3.29), respectively. Conclusions. We found up to a 30% increase in the overall incidence and mortality from KC with NSAID in the general population. This association was attenuated beyond the first year of follow-up and inconsistent in populations with much higher NSAID use.