Mechanisms of triple whammy acute kidney injury

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• 作者：Laura Prieto-Garc&iacute ; a^a ; ^b ; ^d ; ^e ; ^f ; Miguel Pericacho^a ; ^b ; ^d ; Sandra M. Sancho-Mart&iacute ; nez^b ; ^d ; ^e ; ^f ; &Aacute ; ngel S&aacute ; nchez^a ; ^c ; Carlos Mart&iacute ; nez-Salgado^a ; ^b ; ^d ; ^e ; ^f ; Jos&eacute ; Miguel L&oacute ; pez-Novoa^a ; ^b ; ^d ; ^e ; ^f ; Francisco J. L&oacute ; pez-Hern&aacute ; ndez^a ; ^b ; ^d ; ^e ; ^f ; ^{flopezher@usal.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACEI ; Angiotensin-converting enzyme inhibitor ; ADH ; Antidiuretic hormone ; AKI ; Acute kidney injury ; AKIN ; Acute kidney injury network ; ANP ; Atrial natriuretic peptide ; ARA ; Angiotensin receptor antagonist ; AT1 ; Angiotensin type 1 receptor ; AT2 ; Angiotensin type 2 receptor ; ATP ; Adenosine triphosphate ; BP ; Blood pressure ; BR ; Baroreceptor ; cTALH ; thick ascending limb of Henle ; COX ; Cyclooxygenase ; Cr ; Creatinine ; Crpl ; Plasma creatinine concentration ; EPI ; Epinephrin ; GFR ; Glomerular filtration r
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：167
• 期：Complete
• 页码：132-145
• 全文大小：1319 K

文摘

Pre-renal acute kidney injury (AKI) results from glomerular haemodynamic alterations leading to reduced glomerular filtration rate (GFR) with no parenchymal compromise. Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARAs), non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, are highly prescribed drugs that are frequently administered together. Double and triple associations have been correlated with increased pre-renal AKI incidence, termed “double whammy” and “triple whammy”, respectively. This article presents an integrative analysis of the complex interplay among the effects of NSAIDs, ACEIs/ARAs and diuretics, acting alone and together in double and triple therapies. In addition, we explore how these drug combinations alter the equilibrium of regulatory mechanisms controlling blood pressure (renal perfusion pressure) and GFR to increase the odds of inducing AKI through the concomitant reduction of blood pressure and distortion of renal autoregulation. Using this knowledge, we propose a more general model of pre-renal AKI based on a multi whammy model, whereby several factors are necessary to effectively reduce net filtration. The triple whammy was the only model associated with pre-renal AKI accompanied by a course of other risk factors, among numerous potential combinations of clinical circumstances causing hypoperfusion in which renal autoregulation is not operative or is deregulated. These factors would uncouple the normal BP-GFR relationship, where lower GFR values are obtained at every BP value.