「Triple Whammy」（レニン・アンジオテンシン系阻害薬，利尿薬，非ステロイド性抗炎症薬の3剤併用）による腎機能への慢性的な影響

Abstract

Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-in‰ammatory 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 eŠects on the kidney. In this study, we investigated the chronic eŠects 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 conˆrm 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 glomerularˆltration rate (eGFR) decreased signiˆcantly from 62.6 to 58.9 mL/min/1.73 m 2 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 eŠects of individual diŠerences, 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 signiˆcantly reduced (p ＜ 0.01). Therefore, it appears that the``Triple Whammy'' may cause not only AKI but also chronic renal degeneration.

A cross-sectional exploratory survey on occurrence of triple-whammy prescription pattern in Japan

“…We found that 0.3% of the included patients received triple-whammy prescriptions. Although this proportion was lower than the 0.8% reported in a single-center study [4], we think our results are reasonable because the JMDC claims database only covers patients under 75 years of age [6]. Elderly people have a high risk of AKI induced by the triple-whammy, and polypharmacy is common [7,8].…”

“…Drugs were identified by the Anatomical Therapeutic Chemical (ATC) system: NSAIDs (M01A); RAAS blockers (C09A, C09C, and C09D); and Diuretics (C03). RAAS blockers were defined as angiotensin II receptor blockers (ARB) and angiotensin-converting-enzyme inhibitors (ACE-I) [4]. Clinical departments and institutions were extracted from text codes and institution IDs.…”

“…Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), renin-angiotensin-aldosterone system (RAAS) blockers, and diuretics is strongly related to the occurrence of acute kidney injury (AKI); this combination of drugs is called the "triple-whammy" [1][2][3][4]. AKI induced by the triple-whammy is caused by a combination of pharmacological activities: (1) NSAIDs lead to renal afferent arteriolar constriction;…”

Acute Kidney Injury associated with "Triple whammy" combination: a protocol for a systematic review.

“…3 Specifically, the triple association has been associated with an increase of about 30% in the risk of AKI. 4,5 Furthermore, in the case-control study carried out by Lapi et al it was concluded that the risk of developing AKI was higher during the first 30 days of treatment with the triple therapy. 6 AKI has important social and economic consequences.…”

“… 13 Descriptive, cross-sectional, and retrospective studies in Australia 3 , 14 and Japan. 5 Only three investigations carried out in Spain have been identified, 12 , 15 , 16 of which only two analyzed the incidence of AKI, mortality and costs associated with “triple whammy”. The third study analyzed the effect of pharmaceutical interventions on the frequency of prescription of the combination therapy.…”