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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

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Abstract

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.

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Authors and Affiliations

  1. Department of Renal Medicine, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore, 169856, Singapore

    Cynthia Ciwei Lim, Jia Liang Kwek, Su Hooi Teo, Manish Kaushik, Chieh Suai Tan & Jason Chon Jun Choo

  2. SingHealth Polyclinics, Singapore, Singapore

    Ngiap Chuan Tan & Andrew Teck Wee Ang

  3. Health Services Research Unit, Singapore General Hospital, Singapore, Singapore

    Edmund Pek Siang Teo & Hanis Bte Abdul Kadir

  4. Department of Endocrinology, Singapore General Hospital, Singapore, Singapore

    Yong Mong Bee

Authors
  1. Cynthia Ciwei Lim
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Corresponding author

Correspondence to Cynthia Ciwei Lim.

Ethics declarations

Funding

This research was supported by the SHF-Foundation Research Grant (SHF/HSRHO014/2017).

Conflict of interest

All authors declare no relevant conflict of interest.

Ethics approval

This study was conducted according to the Declaration of Helsinki.

Consent

Waiver of informed consent for the use of de-identified electronic medical record data was approved by the SingHealth Centralized Institutional Board (2018/2567).

Consent for publication

Not applicable.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available because data sharing will be subject to institutional approval.

Code availability

Not applicable.

Author contributions

CCL, TNC, and JC conceptualized and designed the study; CL, TNC, HAK, and AA obtained data; CL and ET analyzed and interpreted the data; CL wrote the first draft; all authors contributed to and approved the final version of this manuscript for submission.

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Lim, C.C., Tan, N.C., Teo, E.P.S. et al. 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. Drugs Aging 39, 75–82 (2022). https://doi.org/10.1007/s40266-021-00907-w

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