Are nonsteroidal anti-inflammatory drugs safe for the kidney in ankylosing spondylitis?

Abstract

www.jrd.or.kr Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for controlling pain and inflammation in rheumatic and musculoskeletal diseases. NSAIDs reduce the production of prostaglandin (PG) by inhibiting cyclooxygenase, thereby reducing inflammation. However, PGs are involved in renal hemodynamics to preserve renal blood flow. PGE2 and PGI2 exert vasodilatory action at the afferent arteriole, which maintains glomerular filtration and blood supply to the kidney [1]. Therefore, inhibition of PGs by NSAIDs can cause vasoconstriction of afferent arterioles and leads to renal injury. In addition, PGs also play roles in the regulation of systemic blood volume and blood pressure. By inhibiting natriuresis and diuresis, NSAIDs can cause sodium and water retention and blood pressure elevation [1]. Previous cohort studies have shown that NSAID use can have negative impacts on renal function. Dose-response relationships between NSAID cumulative dose and changes in renal function have been observed in community-based elderly populations [2]. In a retrospective longitudinal cohort study of US Army soldiers, the highest exposure level of NSAIDs was associated with modest but significant increases of acute kidney injury and chronic kidney disease [3]. These findings highlight concerns regarding renal toxicity associated with long-term use of NSAIDs in patients with ankylosing spondylitis (AS). A recent study by Koo et al. [4] published in the Journal of Rheumatic Diseases investigated the relationship between longterm use of NSAIDs and renal function using the electronic medical records of 1,280 patients with AS. NSAID exposure was determined by the Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score for time intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The authors concluded that there was no clinically significant correlation between NSAID Intake Score and change in estimated glomerular filtration rate (eGFR) in AS patients. To interpret the results of this study, some points need to be considered. First, the finding that there was no clinically significant deterioration of renal function in patients treated with higher doses of NSAIDs might be due to channeling bias, where patients with better renal function and less comorbidities may have been prescribed more NSAIDs than those with poorer renal function and more comorbidities. In a Swedish national population-based cohort study of spondyloarthritis patients examining the cardiovascular and renal safety of nonselective NSAIDs and selective COX-2 inhibitors, the relative risk of renal insufficiency was higher in the NSAID-nonexposed group compared with the nonselective NSAID-exposed group, reflecting selection of patients being prescribed NSAIDs [5]. Second, considering the young age of the study population, relatively few patients experienced decline in renal function. In the ASAScomorbidities in spondyloarthritis (COMOSPA) cohort, the prevalence of renal impairment defined as an eGFR <60 mL/ min/1.73 m was 5.2% [6], which was higher than that in a study by Koo et al. [4]. The mean age was 45.3 years in the ASAS-COMOSPA cohort, while much younger patients (mean age, 30.2 years) were included in the present study [4]. Age is a strong risk factor for renal impairment in the general population, as