Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration. METHODS: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days. RESULTS: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs. CONCLUSION: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.

Non-steroidal anti-inflammatory drugs and risk of acute adverse renal outcomes in diabetes and diabetic kidney disease.

BACKGROUND: Individuals with diabetes mellitus (DM) may be susceptible to non-steroidal anti-inflammatory drug (NSAID)-induced acute kidney injury (AKI) but data on NSAID-related adverse renal events is sparse. OBJECTIVE: We aimed to evaluate the risk of acute kidney injury and/or hyperkalemia after systemic NSAID among individuals with DM and diabetic chronic kidney disease (CKD). METHODS: Retrospective cohort study of 3896 adults with DM with incident prescriptions between July 2015 and December 2017 from Singapore General Hospital and SingHealth Polyclinics. Laboratory, hospitalization and medication data were retrieved from electronic medical records. The primary outcome was the incidence of AKI and/ or hyperkalemia within 30 days after prescription. RESULTS: AKI and/or hyperkalemia occurred in 13.5% of all DM and 15.8% of diabetic CKD. The association between systemic NSAID >14 days and 30-day risk of AKI and/or hyperkalemia failed to reach statistical significance in unselected DM (adjusted OR 1.62, 95% CI 0.99-2.65, p = 0.05) and diabetic CKD (adjusted OR 0.64, 95% CI 0.15-2.82, p = 0.64), but the odds of AKI and/or hyperkalemia were markedly and significantly increased when NSAID was prescribed with renin-angiotensin-aldosterone system (RAAS) blocker (adjusted OR 4.17, 95% CI 1.74-9.98, p = 0.001) or diuretic (adjusted OR 3.31, 95% CI 1.09-10.08, p = 0.04) and in the absence of diabetic CKD (adjusted OR 1.98, 95% CI 1.16-3.36, p = 0.01). CONCLUSION: NSAID prescription >14 days in individuals with DM with concurrent RAAS blockers or diuretics was associated with higher 30-day risk of AKI and/or hyperkalemia.

Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model.

AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics among older adults. Adverse effects may be avoided by careful patient selection. We aimed to evaluate the incidence of acute kidney injury (AKI) and/or hyperkalemia, risk factors, and the accuracy of an NSAID risk prediction model in a cohort of Asian older adults. METHODS: We conducted a retrospective cohort study of older adults, age 65 years and above, who received prescriptions between March 2015 and December 2017 from Singapore's largest cluster of public healthcare institutions. Factors associated with 30-day incident acute kidney injury and/or hyperkalemia were evaluated with multivariable regression analysis. Calibration and discrimination of the Nash prediction model were assessed using the Hosmer-Lemeshow goodness-of-fit test and C-statistic, respectively. RESULTS: The primary outcome occurred in 16.7% of 12,798 older adults. Topical NSAIDs (adjusted OR 1.29, 95% CI 1.15-1.45), systemic NSAIDs of 1-14 days' duration (adjusted OR 1.43, 95% CI 1.27-1.62), and systemic NSAIDs > 14 days (adjusted OR 1.84, 95% CI 1.37-2.49) were independently associated with the primary outcome, compared with no NSAID. Diabetes mellitus, cardiovascular disease, lower estimated glomerular filtration rate (eGFR), and diuretics were also independently associated with increased incident AKI and/or hyperkalemia. When applied to older adults with systemic NSAIDs > 14 days (n = 305), the Nash risk model had poor calibration (p < 0.001) and poor discrimination with C-statistic 0.527 (0.438, 0.616). CONCLUSIONS: Longer NSAID duration and systemic compared with topical route were associated with incremental odds for acute renal events. Further studies are required to improve the available risk model to guide NSAID prescriptions in older adults.

Short-Course Systemic and Topical Non-Steroidal Anti-Inflammatory Drugs: Impact on Adverse Renal Events in Older Adults with Co-Morbid Disease.

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.