Chronic Effects on Kidney Function by “Triple Whammy” (Combination of Renin and Angiotensin Type Inhibitor, Diuretic Drug and Nonsteroidal Anti-inflammatory Drug)

Abstract

Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-inflammatory drugs increases the risk of acute kidney injury (AKI). This combination has been dubbed the “Triple Whammy”. However, there have been no reports about its chronic effects on the kidney. In this study, we investigated the chronic effects of the “Triple Whammy” on kidney function. There were 203 outpatients who were prescribed this combination in our hospital for 5 years. We excluded patients who could also confirm the combination in the previous year and patients for whom laboratory data were unavailable, thus, leaving a target patient group of 95 patients. The average estimated glomerular filtration rate (eGFR) decreased significantly from 62.6 to 58.9 mL/min/1.73 m² immediately after administering the combination (p<0.01). Although no patients were diagnosed with AKI within 90 days after being administered the combination, 7.4% of patients exhibited a ≥25% reduction in eGFR compared with that before commencing the combination. Correlation analysis of gender, age, past renal function, and renal function change demonstrated that eGFR before administration of the combination negatively correlated with changes in eGFR (p<0.01). Considering the effects of individual differences, eGFR changes before and after administering the combination were compared using a case-crossover design and eGFR after administering the combination was found to be significantly reduced (p<0.01). Therefore, it appears that the “Triple Whammy” may cause not only AKI but also chronic renal degeneration.