Vitamin D and Arteriovenous Fistulae

Patients requiring hemodialysis following kidney failure need a form of dialysis vascular access in order to undergo the dialysis procedure. Dialysis vascular access dysfunction is an enormous clinical problem. While the best form of vascular access is the arteriovenous fistula (AVF), its primary problem is early, aggressive cellular ingrowth that leads to poor maturation of the vessel, preventing its use for dialysis. Strategies to prevent AVF failure are needed. Vitamin D is a hormone present in all human bodies and is important for good bone formation and immune function. There is new information that links vitamin D to the function of our veins and arteries, which are used in the creation of an arteriovenous fistulae. Our bodies can make vitamin D and can also get vitamin D from our diet. However, a majority of patients with chronic kidney disease and end-stage renal disease (ESRD) have low vitamin D levels (vitamin D deficiency). There are several benefits to correcting low vitamin D levels, however, it is not know whether correcting low vitamin D in the body will lead to better function of the vein and artery used for arteriovenous fistulae creation. The main goal of this pilot study is to examine the role of vitamin D supplementation on AVF maturation and useability for dialysis. Study results will be used to develop larger studies to examine the specific effect that vitamin D supplementation has on the vessels used for AVF creation and whether vitamin D promotes AVF maturation.

Hemodialysis vascular access dysfunction is a major source of morbidity and cost among ESRD patients, accounting for up to 25% of all hospital stays, and 50% of all costs within the first year of initiating dialysis.The AVF provides higher blood flow rates, fewer thrombotic and infectious complications, and lower morbidity and cost compared with prosthetic grafts or central venous catheters.However,up to 50% of newly created AVF's fail to mature sufficiently for chronic hemodialysis use. Clearly, determining factors predictive of poor AVF maturation are important from both patient care and health policy perspectives and are worthy of investigation. Vitamin D has antiproliferative, antioxidant and antiangiogenic properties. The observed association of vitamin D deficiency and increased risk of cardiovascular and peripheral vascular disease may extend to the vasculature used in the creation of an AVF. As renal function worsens, patients with chronic kidney disease (CKD) produce less vitamin D, due to impaired renal conversion of 25-hydroxy- to 1,25-dihydroxyvitamin D by declining renal 1-alpha hydroxylase. As a result, at the time of dialysis initiation,78%-90% of ESRD patients are vitamin D deficient. Until recently, vitamin D deficiency among CKD and ESRD patients was only treated if hyperparathyroidism was present, however, more attention is now paid to nutritional vitamin D deficiency given its association with a range of comorbid conditions.Furthermore, 1,25-dihydroxyvitamin D and its analogue compounds are associated with improved survival in the CKD and ESRD populations. We believe that the observed benefits of vitamin D may improve AVF maturation among a population in which vitamin D deficiency is highly prevalent.

Maturation of an AVF is the ability to stick the AVF with two large bore needles at ≥ 6 consecutive dialysis sessions, and achievement of an AVF blood flow >300 ml/min, assessed at six months following AVF creation.

Inclusion Criteria Patients with patients with end-stage renal disease (ESRD) who are suitable candidates for AVF creation (as assessed by pre-operative vein mapping) and plan to undergo AVF creation are eligible to participate Study subjects must agree to participate in the study and provide written informed consent Age: Study subjects must be > 18 years old Sites: Emory University affiliated hospitals (including Emory University Hospital, Emory Midtown Hospital, Grady Memorial Hospital) and Emory University affiliated outpatient dialysis units Informed consent requirements: All study subjects must agree to participate in the study and provide written informed consent. Exclusion Criteria Age < 18 years Patients with a corrected serum calcium > 10.5 mg/dL within 4 weeks of study screening Current intake of > 2000 IU per day of Vitamin D3 Subjects unable to provide informed consent or who plan to relocate outside of Atlanta during the study duration

Mohamed I, Kamarizan MFA, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev. 2021 Jul 23;7(7):CD002786. doi: 10.1002/14651858.CD002786.pub4.

Wasse H, Huang R, Long Q, Zhao Y, Singapuri S, McKinnon W, Skardasis G, Tangpricha V. Very high-dose cholecalciferol and arteriovenous fistula maturation in ESRD: a randomized, double-blind, placebo-controlled pilot study. J Vasc Access. 2014 Mar-Apr;15(2):88-94. doi: 10.5301/jva.5000187. Epub 2013 Oct 7.

Wasse H, Huang R, Long Q, Singapuri S, Raggi P, Tangpricha V. Efficacy and safety of a short course of very-high-dose cholecalciferol in hemodialysis. Am J Clin Nutr. 2012 Feb;95(2):522-8. doi: 10.3945/ajcn.111.025502. Epub 2012 Jan 11.