Does Thiazolidinedione therapy exacerbate fluid retention in congestive heart failure?

被引:29
作者
Goltsman, Ilia [1 ]
Khoury, Emad E. [1 ]
Winaver, Joseph [1 ]
Abassi, Zaid [1 ,2 ]
机构
[1] Technion, Rappaport Fac Med, Bruce Rappaport, Dept Physiol Biophys & Syst Biol, Haifa, Israel
[2] Rambam Human Hlth Care Campus, Dept Lab Med, Haifa, Israel
关键词
Thiazolidinediones; Peroxisome proliferator-activated receptor-gamma; Congestive heart failure; Diabetes mellitus; Fluid retention; Kidney; ACTIVATED-RECEPTOR-GAMMA; TYPE-2; DIABETIC-PATIENTS; RENIN-ANGIOTENSIN SYSTEM; MESENTERIC RESISTANCE ARTERIES; IMPROVES INSULIN SENSITIVITY; ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL GROWTH-FACTOR; OUTPUT CARDIAC-FAILURE; LOWERS BLOOD-PRESSURE; INDUCIBLE KINASE SGK1;
D O I
10.1016/j.pharmthera.2016.09.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ever-growing global burden of congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM) as well as their co-existence necessitate that anti-diabetic pharmacotherapy will modulate the cardiovascular risk inherent to T2DM while complying with the accompanying restrictions imposed by CHF. The thiazolidinedione (TZD) family of peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists initially provided a promising therapeutic option in T2DM owing to anti-diabetic efficacy combined with pleiotropic beneficial cardiovascular effects. However, the utility of TZDs in T2DM has declined in the past decade, largely due to concomitant adverse effects of fluid retention and edema formation attributed to salt-retaining effects of PPAR gamma activation on the nephron. Presumably, the latter effects are potentially deleterious in the context of pre-existing fluid retention in CHF. However, despite a considerable body of evidence on mechanisms responsible for TZD-induced fluid retention suggesting that this class of drugs is rightfully prohibited from use in CHF patients, there is a paucity of experimental and clinical studies that investigate the effects of TZDs on salt and water homeostasis in the CHF setting. In an attempt to elucidate whether TZDs actually exacerbate the pre-existing fluid retention in CHF, our review summarizes the pathophysiology of fluid retention in CHF. Moreover, we thoroughly review the available data on TZD-induced fluid retention and proposed mechanisms in animals and patients. Finally, we will present recent studies challenging the common notion that TZDs worsen renal salt and water retention in CHF. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:75 / 97
页数:23
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