Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD

Eric Yuk Fai Wan; Esther Yee Tak Yu; Linda Chan; Anna Hoi Ying Mok; Yuan Wang; Esther Wai Yin Chan; Ian Chi Kei Wong; Cindy Lo Kuen Lam

doi:10.2215/CJN.18501120

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Abstract

Background and objectives There have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m² and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population.

Design, setting, participants, & measurements From 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m² were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient’s baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m² or eGFR decline ≥30% with reference to baseline.

Results After a median follow-up duration of 6.3 (interquartile range, 3.3–9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m² and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient’s baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m² (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m² (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m² (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41).

Conclusions Nonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m² and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen.

Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3

Received November 29, 2020.
Accepted March 4, 2021.

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