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Current Hypertension Reviews
ISSN (Print): 1573-4021
ISSN (Online): 1875-6506
VOLUME: 9
ISSUE: 2
DOI: 10.2174/15734021113099990006









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

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Author(s): Gopala K. Rangan and David C. Harris
Pages 115-120 (6)
Abstract:
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.
Affiliation:
Centre for Transplant and Renal Research, Level 2, Clinical Sciences Block, Westmead Hospital, Cnr Bridge and Darcy Roads, Westmead, NSW, Australia 2145.