Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

doi:10.1111/jgs.16961

Multicenter Study

. 2021 Mar;69(3):726-734.

doi: 10.1111/jgs.16961. Epub 2020 Dec 10.

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

Jonathan G Amatruda^{1

2}, Ronit Katz³, Carmen A Peralta^{1

2

4}, Michelle M Estrella^{2

5}, Harini Sarathy^{1

6}, Linda F Fried^{7

8}, Anne B Newman⁷, Chirag R Parikh⁹, Joachim H Ix^{10

11}, Mark J Sarnak¹², Michael G Shlipak^{2

13}; Health ABC Study

Affiliations

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.

PMID: 33305369
PMCID: PMC8021485
DOI: 10.1111/jgs.16961

Multicenter Study

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

Jonathan G Amatruda et al. J Am Geriatr Soc. 2021 Mar.

. 2021 Mar;69(3):726-734.

doi: 10.1111/jgs.16961. Epub 2020 Dec 10.

Authors

Affiliations

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.

PMID: 33305369
PMCID: PMC8021485
DOI: 10.1111/jgs.16961

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.

Keywords: NSAID; chronic kidney disease; nephrotoxicity; pharmacoepidemiology.

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Conflict of interest statement

Disclosures & Conflicts of Interest

Dr. Shlipak serves as a scientific advisor to TAI Diagnostics and reports equity in that venture, which falls outside of the submitted work. Dr. Peralta is Chief Medical Officer at Cricket Health. The other authors report no relevant disclosures.

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References

1. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550 - DOI - PMC - PubMed
1. Pathan SA, Mitra B, Cameron PA. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic. European Urology. 2018//04/ 2018;73(4):583–595. doi:10.1016/j.eururo.2017.11.001 - DOI - PubMed
1. Busse JW, Wang L, Kamaleldin M, et al. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA. 2018//12/18 2018;320(23):2448–2460. doi:10.1001/jama.2018.18472 - DOI - PMC - PubMed
1. Gross JL, Perate AR, Elkassabany NM. Pain Management in Trauma in the Age of the Opioid Crisis. Anesthesiol Clin. March 2019;37(1):79–91. doi:10.1016/j.anclin.2018.09.010 - DOI - PubMed
1. Wick EC, Grant MC, Wu CL. Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review. JAMA surgery. 2017//07/01 2017;152(7):691–697. doi:10.1001/jamasurg.2017.0898 - DOI - PubMed

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[1] Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550 - DOI - PMC - PubMed

[2] Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550 - DOI - PMC - PubMed

[3] Pathan SA, Mitra B, Cameron PA. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic. European Urology. 2018//04/ 2018;73(4):583–595. doi:10.1016/j.eururo.2017.11.001 - DOI - PubMed

[4] Pathan SA, Mitra B, Cameron PA. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic. European Urology. 2018//04/ 2018;73(4):583–595. doi:10.1016/j.eururo.2017.11.001 - DOI - PubMed

[5] Busse JW, Wang L, Kamaleldin M, et al. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA. 2018//12/18 2018;320(23):2448–2460. doi:10.1001/jama.2018.18472 - DOI - PMC - PubMed

[6] Busse JW, Wang L, Kamaleldin M, et al. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA. 2018//12/18 2018;320(23):2448–2460. doi:10.1001/jama.2018.18472 - DOI - PMC - PubMed

[7] Gross JL, Perate AR, Elkassabany NM. Pain Management in Trauma in the Age of the Opioid Crisis. Anesthesiol Clin. March 2019;37(1):79–91. doi:10.1016/j.anclin.2018.09.010 - DOI - PubMed

[8] Gross JL, Perate AR, Elkassabany NM. Pain Management in Trauma in the Age of the Opioid Crisis. Anesthesiol Clin. March 2019;37(1):79–91. doi:10.1016/j.anclin.2018.09.010 - DOI - PubMed

[9] Wick EC, Grant MC, Wu CL. Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review. JAMA surgery. 2017//07/01 2017;152(7):691–697. doi:10.1001/jamasurg.2017.0898 - DOI - PubMed

[10] Wick EC, Grant MC, Wu CL. Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review. JAMA surgery. 2017//07/01 2017;152(7):691–697. doi:10.1001/jamasurg.2017.0898 - DOI - PubMed

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Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

Affiliations

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

Authors

Affiliations

Abstract

Conflict of interest statement

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Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous