title: Rationale and design of an observational study to determine the effects of cholecalciferol on hypertension, proteinuria and urinary MCP-1 in ADPKD.
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.
authors: Centre for Transplant and Renal Research, Westmead Millennium Institute, Sydney Medical School – Westmead, The University of Sydney, Sydney, Australia. g.rangan@sydney.edu.au
authors: Gopala K
authors: GK
authors: Rangan
authors: David C
authors: DC
authors: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia; D015415:Biomarkers / Q000652:urine*; D018932:Chemokine CCL2 / Q000652:urine*; D002762:Cholecalciferol / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000652:urine; D011507:Proteinuria / Q000188:drug therapy* / Q000652:urine; D012107:Research Design; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D014807:Vitamin D; D002762:Cholecalciferol