Use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a higher risk of nephrotic syndrome, new study findings suggest.

“A patient who develops nephrotic syndrome should be asked about the use of NSAIDs, including over the counter,” Mohammad Bakhriansyah, MD, of Utrecht University in Utrecht, The Netherlands, and colleagues concluded in a paper published in the Clinical Journal of the American Society of Nephrology.

In a matched case-control study, the investigators found that current use (use at the nephrotic syndrome diagnosis date) of conventional NSAIDs for 15 to 28 days and more than 28 days was associated with significant 34% and 42% increased odds of nephrotic syndrome, respectively, compared with nonuse, in adjusted analyses. Recent use of conventional NSAIDs (discontinuation of the drugs 1 to 2 months before the date of nephrotic syndrome diagnosis) was associated with significant 55% increased odds of nephrotic syndrome. Past use (discontinuation of NSAIDs 2 months to 2 years before the diagnosis date) was associated with significant 24% increased odds.

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The study found no significant association between nephrotic syndrome and current NSAID use for less than 15 days and past use defined by NSAID discontinuation more than 2 years before the diagnosis date.

In addition, categorization based on chemical groups revealed that recent acetic acid derivative use was significantly associated with a nearly 2-fold increased odds of nephrotic syndrome compared with nonuse in adjusted analyses, whereas recent use of propionic acid derivatives and other conventional NSAIDs were not significantly associated with nephrotic syndrome. Past use (discontinuation of NSAIDs 2 months to 2 years before the diagnosis date) of acetic acid derivatives and propionic acid derivatives were significantly associated with 36% and 14% increased odds of nephrotic syndrome, respectively, compared with nonuse. The study found no significant association between past use of other conventional NSAIDs and selective COX-2 inhibitors.

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The study included 2620 cases (patients with a first diagnosis of nephrotic syndrome) and 10,454 controls (patients without nephrotic syndrome) identified using the UK primary care database. The mean ages of cases and controls were 58 and 57 years, respectively.

With respect to study strengths, the investigators noted that they extracted data over a long observation time and the database contained longitudinal data of patients’ medical history and lifestyle. “Many potential risk factors were available, allowing us to adjust for many potential confounders,” they wrote.

The investigators acknowledged study limitations, including the possibility of a delay in establishing the diagnosis of nephrotic syndrome from patients’ first complaints. “The index date was the date of diagnosis entered into the database, whereas the first complaints that cause patients to seek help might have preceded this index date,” Dr Bakhriansyah and colleagues pointed out. If the delay is substantial—and weeks to months are not uncommon in nephrotic syndrome—and patients take an NSAID within this period, it inadvertently attributes to misclassification of the exposure status, they explained.


Bakhriansyah M, Souverein PC, van den Hoogen MWF, et al. Risk of nephrotic syndrome for non-steroidal anti-inflammatory drug users. Clin J Am Soc Nephrol. 2019; doi: 10.2215/CJN.14331218