Jonathan G Amatruda1,2, Ronit Katz3, Carmen A Peralta1,2,4, Michelle M Estrella2,5, Harini Sarathy1,6, Linda F Fried7,8, Anne B Newman7, Chirag R Parikh9, Joachim H Ix10,11, Mark J Sarnak12, Michael G Shlipak2,13. 1. Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. 2. Kidney Health Research Collaborative, San Francisco VA Medical Center & University of California, San Francisco, San Francisco, California, USA. 3. Kidney Research Institute, University of Washington, Seattle, Washington, USA. 4. Chief Medical Office, Cricket Health, Inc., San Francisco, California, USA. 5. Division of Nephrology, Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA. 6. Division of Nephrology, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, California, USA. 7. University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, USA. 8. VA Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. 9. Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. 10. Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, California, USA. 11. Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California, USA. 12. Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA. 13. Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA.
Abstract
BACKGROUND/ OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Multicenter, community-based cohort. PARTICIPANTS: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. EXPOSURE: Prescription and over-the-counter NSAID use ascertained by self-report. MEASUREMENTS: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. RESULTS: Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year). CONCLUSION: Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.
BACKGROUND/ OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Multicenter, community-based cohort. PARTICIPANTS: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. EXPOSURE: Prescription and over-the-counter NSAID use ascertained by self-report. MEASUREMENTS: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. RESULTS:Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year). CONCLUSION: Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.
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