Rationale and Design of an Observational Study to Determine the Effects of Cholecalciferol on Hypertension, Proteinuria and Urinary MCP-1 in ADPKD

Author(s): Gopala K. Rangan, David C. Harris

Journal Name: Current Hypertension Reviews

Volume 9 , Issue 2 , 2013

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure in the world. Currently there are no treatments to prevent kidney due to ADPKD. Vitamin D is traditionally known for its role in maintaining calcium balance and normal bone health, but it is being increasingly being recognised for a number of other important physiological functions, including reducing blood pressure and proteinuria as well as kidney inflammation andfibrosis. Vitamin D deficiency is associated with proteinuria, increased mortality and may mediate the progression to kidney failure. Recent data from an Australian cohort study (AusDiab) reveals that vitamin D deficiency and insufficiency are common conditions, affecting 26.6% and 42.1% of the Australian community respectively. Preclinical studies from our laboratory have identified that vitamin D deficiency exacerbates proteinuria and hypertension in experimental PKD, and that this is reversed by treatment with vitamin D receptor agonist. In this manuscript, we report the rational and design of an open-label observational study of humans with ADPKD (eGFR>30 ml/min/1.73m2). All subjects will undergo screening for vitamin D levels at the beginning of study, and those that are found to be either deficient (<50 nmol/L) or insufficient (<75 nmol/L) will be repleted with oral cholecalciferol for 6 months. We predict that cholecalciferol will attenuate hypertension, proteinuria and reduce the urinary excretion of a biomarker, monocyte chemoattractant protein-1 (MCP-1, a surrogate inflammatory marker of progression in ADPKD). This study will provide evidence as to whether a simple intervention such as vitamin D repletion, in either deficient or insufficient states, is a treatment to prevent kidney failure in ADPKD.

Keywords: Vitamin D, polycystic kidney disease, progression.

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Article Details

Year: 2013
Page: [115 - 120]
Pages: 6
DOI: 10.2174/15734021113099990006
Price: $65

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PDF: 30