The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Abstract

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a “controversies conference” on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D “adequacy” as concentrations > 20 ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15 ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20 ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

“…Low serum 25(OH)D 3 values are associated with muscle weakness and increased risk of falls in patients on dialysis, independent of 1,25(OH) 2 D 3 values . Concentration of serum 25(OH)D 3 exhibited significant seasonal variation, and deficiency of 25(OH)D 3 is common in patients with chronic kidney disease and is associated with poor outcomes such as progression to end‐stage kidney disease, infections, fracture rates, hospitalizations, and all‐cause mortality . Apart from the classical VDR signalling pathway, other cytosol receptors such as annexin II and membrane‐associated rapid response steroid‐binding proteins could induce rapid effects of vitamin D in muscle .…”

“…16 Concentration of serum 25(OH)D 3 exhibited significant seasonal variation, and deficiency of 25(OH)D 3 is common in patients with chronic kidney disease and is associated with poor outcomes such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. 17,18 Apart from the classical VDR signalling pathway, other cytosol receptors such as annexin II and membrane-associated rapid response steroid-binding proteins could induce rapid effects of vitamin D in muscle. 19,20 In this study, we investigated the effects of vitamin D repletion in a mouse model of INC-associated cachexia, with particular focus on adipose tissue browning and muscle wasting.…”

Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D3 kinetics for extrapolation from mouse to man: Commentary

“…With regard to cardiovascular disease, large epidemiological studies have routinely highlighted a link between vitamin D insufficiency or deficiency and increased risks of hypertension (Ke, Mason, Kariuki, Mpofu, & Brock, 2015), promotion of atherosclerosis (Kunadian, Ford, Bawamia, Qiu, & Manson, 2014; Nsengiyumva et al, 2015), chronic kidney disease (CKD) progression (Junarta, Jha, & Banerjee, 2019; Melamed et al, 2018), and cardiovascular mortality and morbidity (Wang, 2016; Wang et al, 2012). Vitamin D‐mediated suppression of the renin‐angiotensin‐aldosterone system (RAAS) appears to be the most likely mechanism through which vitamin D exerts its potential cardiovascular benefits.…”

The Role of Vitamin D and Oxidative Stress in Chronic Kidney Disease

“…Thus, the 24,25(OH) 2 D to 25D ratio [vitamin D metabolite ratio (VMR)] may reflect free circulating 25D and could represent a more physiologically precise measure of bioactive 25D that should be independent of racial/ethnic differences in vitamin D binding protein levels and/or polymorphisms. Thus, the VMR may represent a new candidate biomarker for vitamin D status Thus, modestly lower levels of serum 25D in African Americans may not require treatment and differing rates of these polymorphisms in different clinical studies may contribute to the conflicting outcomes following vitamin D administration.Observational studies have linked low 25D levels in patients with CKD to progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality 43. A recent panel convened by the National Kidney Foundation recommended patients with CKD and 25D levels less than 15 ng/mL should be treated, while those with serum 25D levels between 15 and 20 ng/mL may not require treatment unless there is evidence of counter-regulatory hormone activity 43.…”

“…Thus, the VMR may represent a new candidate biomarker for vitamin D status Thus, modestly lower levels of serum 25D in African Americans may not require treatment and differing rates of these polymorphisms in different clinical studies may contribute to the conflicting outcomes following vitamin D administration.Observational studies have linked low 25D levels in patients with CKD to progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality 43. A recent panel convened by the National Kidney Foundation recommended patients with CKD and 25D levels less than 15 ng/mL should be treated, while those with serum 25D levels between 15 and 20 ng/mL may not require treatment unless there is evidence of counter-regulatory hormone activity 43. Whether evidence of increased oxidative stress and inflammation are other indicators of increased risk requiring treatment at modestly low serum levels is still to be determined.…”