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The Concomitant Use of Diuretics, Non-Steroidal Anti-Inflammatory Drugs, and Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers (Triple Whammy), Extreme Heat, and In-Hospital Acute Kidney Injury in Older Medical Patients



We investigated whether the concomitant use of diuretics, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (triple whammy, TW) predicts in-hospital acute kidney injury (AKI) and whether admission during recorded periods of extreme heat influences this association.


We retrospectively collected data on patient characteristics and use of TW/non-TW drugs on admission, AKI (increase in serum creatinine ≥ 27 µmol/l either within the first 48 h of admission or throughout hospitalization, primary outcome), length of stay (LOS), and mortality (secondary outcomes) in medical patients ≥65 years admitted (1) during five consecutive heat waves (HWs) between 2007 and 2009 (n = 382) or (2) either before or after each HW, matched for HW period, age, and admission day of the week (non-HW, controls, n = 1339).


Number of TW and non-TW drugs, co-morbidities, number of daily admissions, incidence of in-hospital AKI, LOS, and mortality were similar in the HW and non-HW groups. After adjusting for clinical and demographic confounders, logistic regression showed that TW use did not predict AKI within 48 h of admission either during non-HW periods (OR 0.79, 95% CI 0.34–1.83, P = 0.58) or during HWs (OR 1.02, 95% CI 0.21–2.97, P = 0.97). Similar results were observed when AKI was captured throughout hospitalization. TW use did not predict LOS or mortality irrespective of environmental temperature on admission.


TW use on admission did not predict in-hospital AKI, LOS, or mortality in older medical patients admitted either during periods of normal environmental temperature or during HWs.

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This study was supported by a Research Grant from the Faculty of Medicine, Nursing, and Health Sciences, Flinders University (ref 01.601.38927). The article processing charges were funded by the authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. The data sets analyzed during the current study are available from the corresponding author on reasonable request.


Arduino A. Mangoni, Feruza Kholmurodova, Lidia Mayner, Paul Hakendorf and Richard J. Woodman have nothing to disclose.

Compliance with ethics guidelines

The study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (HREC/14/SAC).

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Correspondence to Arduino A. Mangoni.

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Mangoni, A.A., Kholmurodova, F., Mayner, L. et al. The Concomitant Use of Diuretics, Non-Steroidal Anti-Inflammatory Drugs, and Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers (Triple Whammy), Extreme Heat, and In-Hospital Acute Kidney Injury in Older Medical Patients. Adv Ther 34, 2534–2541 (2017).

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  • Acute kidney injury
  • Heat waves
  • Length of stay
  • Mortality
  • Nephrology
  • Triple whammy