Cynthia Ciwei Lim1, Andrew Teck Wee Ang2, Hanis Bte Abdul Kadir3, Puay Hoon Lee4,5, Bandy Qiuling Goh2, Sudha Harikrishnan5, Jia Liang Kwek6, Sheryl S W Gan6, Jason Chon Jun Choo6, Ngiap Chuan Tan2. 1. Department of Renal Medicine, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore, 169856, Singapore. cynthia.lim.c.w@singhealth.com.sg. 2. SingHealth Polyclinic, Singapore, Singapore. 3. Health Services Research Unit, Singapore General Hospital, Singapore, Singapore. 4. Pharmacy, Singapore General Hospital, Singapore, Singapore. 5. Health Service Research Center, SingHealth, Singapore, Singapore. 6. Department of Renal Medicine, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore, 169856, Singapore.
Abstract
BACKGROUND: Prolonged systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with adverse renal outcomes among older adults. However, there is scant data regarding the renal safety of topical and short-course systemic NSAIDs. We aimed to evaluate the risk of acute adverse renal outcomes among older adults prescribed topical and short-term systemic NSAIDs. METHODS: We conducted a retrospective cohort study of all older adults, age 60 years and above, who received prescriptions between July 2015 and December 2017 from the largest tertiary hospital and a major public primary care institution in Singapore. Data from 6 months before until 30 days after the first prescription were retrieved from electronic medical records. The primary outcome was the incidence of acute kidney injury (serum creatinine increased >26.5 µmol/L or >50% from baseline) and/or hyperkalemia within 30 days. A multi-variate analysis taking into account age, sex, co-morbidities, baseline-estimated glomerular filtration rate and serum potassium, NSAID route of administration, and concurrent renin-angiotensin-aldosterone system blocker and diuretic prescription was performed to evaluate factors associated with the primary outcome. RESULTS: We identified 12,773 older adults with incident prescriptions: 3982 (31.2%) received short-course systemic NSAIDs, 3784 (29.6%) received topical NSAIDs, and 5007 (39.2%) did not receive any NSAID. Both short-course systemic NSAIDs (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.41-1.80, p < 0.001) and topical NSAIDs (adjusted OR 1.48, 95% CI 1.31-1.67, p < 0.001), compared with the no-NSAID group, were independently associated with the primary outcome. Among older adults with co-morbid conditions and prescribed NSAIDs, topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in diabetes mellitus (adjusted OR 0.78, 95% CI 0.65-1.06, p = 0.007), chronic kidney disease (adjusted OR 0.74, 95% CI 0.60-0.90, p = 0.003), and cardiovascular disease (adjusted OR 0.54, 95% CI 0.37-0.79, p < 0.001), compared with short-course systemic NSAIDs. CONCLUSIONS: NSAIDs increased the risk of acute adverse renal events. Topical NSAIDs, compared with short-course systemic NSAIDs, were associated with a reduced incidence of acute kidney injury and/or hyperkalemia among older adults with additional risk factors.
BACKGROUND: Prolonged systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with adverse renal outcomes among older adults. However, there is scant data regarding the renal safety of topical and short-course systemic NSAIDs. We aimed to evaluate the risk of acute adverse renal outcomes among older adults prescribed topical and short-term systemic NSAIDs. METHODS: We conducted a retrospective cohort study of all older adults, age 60 years and above, who received prescriptions between July 2015 and December 2017 from the largest tertiary hospital and a major public primary care institution in Singapore. Data from 6 months before until 30 days after the first prescription were retrieved from electronic medical records. The primary outcome was the incidence of acute kidney injury (serum creatinine increased >26.5 µmol/L or >50% from baseline) and/or hyperkalemia within 30 days. A multi-variate analysis taking into account age, sex, co-morbidities, baseline-estimated glomerular filtration rate and serum potassium, NSAID route of administration, and concurrent renin-angiotensin-aldosterone system blocker and diuretic prescription was performed to evaluate factors associated with the primary outcome. RESULTS: We identified 12,773 older adults with incident prescriptions: 3982 (31.2%) received short-course systemic NSAIDs, 3784 (29.6%) received topical NSAIDs, and 5007 (39.2%) did not receive any NSAID. Both short-course systemic NSAIDs (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.41-1.80, p < 0.001) and topical NSAIDs (adjusted OR 1.48, 95% CI 1.31-1.67, p < 0.001), compared with the no-NSAID group, were independently associated with the primary outcome. Among older adults with co-morbid conditions and prescribed NSAIDs, topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in diabetes mellitus (adjusted OR 0.78, 95% CI 0.65-1.06, p = 0.007), chronic kidney disease (adjusted OR 0.74, 95% CI 0.60-0.90, p = 0.003), and cardiovascular disease (adjusted OR 0.54, 95% CI 0.37-0.79, p < 0.001), compared with short-course systemic NSAIDs. CONCLUSIONS: NSAIDs increased the risk of acute adverse renal events. Topical NSAIDs, compared with short-course systemic NSAIDs, were associated with a reduced incidence of acute kidney injury and/or hyperkalemia among older adults with additional risk factors.
Authors: Sharon X Lin; Thomas Phillips; David Culliford; Christopher Edwards; Christopher Holroyd; Kinda Ibrahim; Ravina Barrett; Clare Howard; Ruth Johnson; Jo Adams; Mathew Stammers; Adam Rischin; Paul Rutter; Nicola Barnes; Paul J Roderick; Simon Ds Fraser Journal: BJGP Open Date: 2022-03-22