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Peroxisome proliferator-activated receptor-alpha agonists in the management of the diabetic acute kidney injury: Is the verdict out?

Volume No : (2018) Volume: 06 Issue : 31 Year : 2018 Page No: 37-41

Authors : Vishal Arvind Chakkarwar, P. S. Kawtikwar

Abstract :

The growing evidence of diabetic acute kidney injury (AKI) suggested that diabetes is one of the detrimental causes. AKI is associated with glomerular hypertrophy, glomerulosclerosis, tubulointerstitial fibrosis, and mesangial cell expansion followed by albuminuria and reduction in glomerular filtration rate. Indeed, no promising therapeutic options are available in the present clinical scenario to manage efficiently the AKI. However, angiotensin-converting enzyme inhibitors and angiotensin-II-AT (1)  receptor blockers are currently employed to improve the structural and functional status of the AKI.  These interventions, however, are not optimal in improving overall outcomes of AKI. Hence, there is a continuing need for developing promising therapeutic interventions to manage this insidious condition adequately. Recent bench and clinical studies strongly suggest the potentials of peroxisome proliferator-activated receptor alpha (PPAR-α) agonists in the management of AKI by keeping the view that renal lipid accumulation-induced lipotoxicity is one of the risk factors for nephropathy during chronic diabetes mellitus. As inflammation, oxidative stress and dyslipidemia are common consequences of renal dysfunction, PPAR-α agonists could serve as promising therapeutic agents for controlling the progression of AKI. In fact, fenofibrate, a hypolipidemic agent acts as a PPAR-α agonist, reduced renal lipotoxicity, inflammation, fibrosis, and oxidative stress, and subsequently prevented the symptoms of diabetic nephropathy. However, fenofibrate has been shown to cause renal dysfunction in established renal disorders. The present review addressed the rationale of employing  PPAR-α agonists in the management of AKI.

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