Vitamin D is characterized as a regulator of homeostasis of bone and mineral metabolism, but it can also provide nonskeletal actions because vitamin D receptors have been found in various tissues including the brain, prostate, breast, colon, pancreas, and immune cells. Bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation are all biological functions of vitamin D. Vitamin D may play an important role in modifying the risk of cardiometabolic outcomes, including diabetes mellitus (DM), hypertension, and cardiovascular disease. The incidence of type 2 DM is increasing worldwide and results from a lack of insulin or inadequate insulin secretion following increases in insulin resistance. Therefore, it has been proposed that vitamin D deficiency plays an important role in insulin resistance resulting in diabetes. The potential role of vitamin D deficiency in insulin resistance has been proposed to be associated with inherited gene polymorphisms including vitamin D-binding protein, vitamin D receptor, and vitamin D 1alpha-hydroxylase gene. Other roles have been proposed to involve immunoregulatory function by activating innate and adaptive immunity and cytokine release, activating inflammation by upregulation of nuclear factor κB and inducing tumor necrosis factor α, and other molecular actions to maintain glucose homeostasis and mediate insulin sensitivity by a low calcium status, obesity, or by elevating serum levels of parathyroid hormone. These effects of vitamin D deficiency, either acting in concert or alone, all serve to increase insulin resistance. Although there is evidence to support a relationship between vitamin D status and insulin resistance, the underlying mechanism requires further exploration. The purpose of this paper was to review the current information available concerning the role of vitamin D in insulin resistance.

Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.

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At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

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Maintenance haemodialysis patients with symptoms of depression may have higher serum IL-6 and lower serum albumin levels. The prevalence of depression was lower in elderly patients at or above 75 years old, and no correlation was found with socio-economic status. Factors including co-morbid conditions, serum IL-6, albumin and age may help predict which patients may be predisposed to develop symptoms of depression.

As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling ‐ scenario, which is known as CKD‐mineral bone disease (MBD). CKD‐MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft‐tissue calcifications, either vascular or extra‐osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD‐MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.