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

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.

Relative risks of adverse events among older adults receiving opioids versus NSAIDs after hospital discharge: A nationwide cohort study

“…Although we adjusted for several predictors of renal failure, including preexisting chronic kidney disease (CKD), prior episodes of acute renal failure, and use of angiotensin converting enzyme inhibitors and receptor blockers, it is still possible that our results reflect confounding by the fact that physicians tend to avoid NSAIDs in patients at high risk for adverse renal effects. However, a recent analysis of older adults did not find increased risk of kidney dysfunction or injury among those who reported taking NSAIDs [ 26 ]. Another recent analysis of patients with CKD found that opioid use had a stronger association with renal adverse events than NSAIDs [ 27 ].…”

Correlation between perioperative parecoxib use and postoperative acute kidney injury in patients undergoing radical mastectomy: a retrospective cohort analysis

“…And another meta-analysis demonstrated selective COX-2 inhibitors was related with the increasing risk of AKI [23]. However, a study revealed that there were no statistical differences in kidney function between the groups with and without NSAIDs among elderly patients [24]. Even more, a prospective and multicenter study by STARSurg showed that NSAIDs in the postoperative was safer for the patients undergoing gastrointestinal surgery.…”

NSAID use in orthopedic surgery: A review of current evidence and clinical practice guidelines

“…CKD is a major cause of morbidity and mortality, both in the United States and worldwide, and its incidence is expected to increase following the anticipated increase in both obesity and diabetes. However, similar to studies examining normotensive patients, there is substantial evidence that NSAIDs do not cause moderate or severe CKD 67 nor progression of pre‐existing CKD 68–70 . While some published studies have shown a link between NSAID use and moderate to severe CKD, 16,17 these studies have had small sample sizes and were lower quality than those who show no link 69,70 .…”

“…Similarly, multiple studies have shown that neither selective nor nonselective NSAIDs affect blood pressure or renal function in patients without hypertension 65,66 . This has been found to be true even in older adults, as self‐reported use of NSAIDs was not associated with kidney dysfunction or kidney injury in ambulatory patients with a mean age of 74 67 …”

“…65,66 This has been found to be true even in older adults, as self-reported use of NSAIDs was not associated with kidney dysfunction or kidney injury in ambulatory patients with a mean age of 74. 67 Perhaps more closely considered is the development or progression of chronic kidney disease (CKD). CKD is a major cause of morbidity and mortality, both in the United States and worldwide, and its incidence is expected to increase following the anticipated increase in both obesity and diabetes.…”