Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study

Abstract

Background: Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim: The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods: A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results: Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions: The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

Fig 1. Selection of cases and controls.

Fig 2. Association between NSAIDs and risk of CKD, stratified by classes and time windows.

NSAID = non-steroidal anti-inflammatory drug; ID = index date; OR = odds ratio. OR was adjusted for malignant neoplasm, ischemic heart disease, diabetes mellitus, liver disease, gout, dyslipidemia, hypertension, cerebrovascular disease, lupus erythematosus systemic (LES), amyloidosis, vasculitis, myeloma, polycystic kidney, prior use of nephrotoxic drugs (other than NSAIDs). Oxicam: piroxicam, meloxicam, lornoxicam, tenoxicam; Acetic acid derivatives and related substances: aceclofenac, ketorolac, acemetacin, etodolac, diclofenac, diclofenac and combinations; Coxib: celecoxib and etoricoxib; Propionic and derivatives: ibuprofen, naproxen, ketoprofen, dexibuprofen, tiaprofenic acid, dexketoprofen, naproxen and esomeprazole; Other anti-inflammatory and anti-rheumatic agents, non-steroids: nimesulide, niflumic acid, acetylsalicylic acid, acetylsalicylic acid combinations excl. psycholeptics; More than one NSAID drug: at least two different drugs belonging to different classes prescribed during the observed time window.

Fig 3. Association between individual NSAIDs and risk of CKD, stratified by time windows.

NSAID = non-steroidal anti-inflammatory drug; ID = index date; OR = odds ratio. OR was adjusted for malignant neoplasm, ischemic heart disease, diabetes mellitus, liver disease, gout, dyslipidemia, hypertension, cerebrovascular disease, lupus erythematosus systemic (LES), amyloidosis, vasculitis, myeloma, polycystic kidney, prior use of nephrotoxic drugs (other than NSAIDs); Coxib: celecoxib and etoricoxib; Others: tenoxicam, aceclofenac, tiaprofenic acid, acetylsalicylic acid, acetylsalicylic acid combinations excl. psycholeptics, niflumic acid; More than one NSAID: at least two different drugs prescribed during the observed time window.

Fig 4. Effect of cumulative exposure to piroxicam, meloxicam, ketorolac and NSAIDs as a whole among current users on the CKD risk.

NSAID = non-steroidal anti-inflammatory drug; ID = index date; OR = odds ratio. OR was adjusted for malignant neoplasm, ischemic heart disease, diabetes mellitus, liver disease, gout, dyslipidemia, hypertension, cerebrovascular disease, lupus erythematosus systemic (LES), amyloidosis, vasculitis, myeloma, polycystic kidney, prior use of nephrotoxic drugs (other than NSAIDs).