Introduction
Vitamin D, a crucial component in the human body, holds significant importance in maintaining health and combating illnesses. It falls under the category of fat-soluble secosteroids and can be obtained through dietary sources or the skin's exposure to sunlight, where it transforms 7-dehydroxycholesterol into its precursor. Alternatively, bio-activation occurs, producing the active form of vitamin D (vitamin D3), which is involved in numerous essential functions such as regulating calcium levels, promoting bone health, influencing fertility, controlling glucose levels, and aiding in detoxification. This article explains vitamin D and kidney damage.
What Is Vitamin D?
Vitamin D plays multiple roles in the normal functioning and metabolism of the kidneys. Studies have shown its crucial impact on kidney disease, with deficiency leading to kidney dysfunction and subsequent renal disorders. Beyond its direct influence on kidney health, research has explored the connection between adipocytes, adipokines, vitamin D, and kidney function. Various studies have delved into the significant role of vitamin D in kidney disease, highlighting its pivotal function in kidney function and metabolism. Further investigation could unveil more detailed insights into the precise relationship between vitamin D and kidney disorders.
Initially, vitamin D is synthesized from 7-hydrocholesterol in the skin and transported to the liver via its transporter, vitamin D-binding protein (DBP). The first hydroxylation converts the vitamin D precursor into 25-hydroxyvitamin D (25(OH)D), the inactive form of vitamin D. Subsequently, it is transported to the kidney, where it undergoes the second hydroxylation, producing 1,25-dihydroxy vitamin D (1,25(OH)D), the active form of vitamin D.
This active circulating form binds to DBP in the plasma. It influences various targets through the vitamin D receptor (VDR). The half-life of vitamin D in the body is approximately three weeks and should be supplemented either through diet or sunlight exposure. Vitamin D exerts its effects through genomic reactions and protein synthesis via its specific receptor (VDR) or through non-genomic actions via another receptor called the 1,25D3-membrane-associated, rapid response steroid-binding receptor (MARRS) (ERp57).
Vitamin D regulates genes responsible for bone remodeling, fertility, and glucose control in bone. Optimal vitamin D concentrations facilitate bone formation, while higher levels limit resorption and mineralization, affecting bone structure. Vitamin D has both catabolic and anabolic functions on bone, attenuating osteoblast genesis (as opposed to parathyroid hormone) and promoting osteoblast survival, growth, and migration. Vitamin D promotes calcium absorption in the small intestine through active (transcellularly in the duodenum) and passive (paracellularly across the length of the small intestine) mechanisms. Vitamin D receptor (VDR) is expressed at higher levels in colonocytes and skin compared to other tissues like the intestine, kidney, and bone. Vitamin D affects colonocyte detoxification by affecting detoxification-related genes, including CYPs, SULTs, and ABC transporters mRNA.
What Is the Physiology of Vitamin D?
The changes in vitamin D metabolism, calcium and phosphate balance, and bone metabolism in chronic kidney disease (CKD) are complex and linked to CKD-MBD (mineral and bone disorder). A large proportion, 70 to 80 %, of CKD patients have plasma 25(OH)D levels below 50 nmol/L, with most falling well below the recommended level for those with renal impairment (>75 nmol/L) if untreated. Various factors contribute to the high prevalence of vitamin D deficiency in CKD patients, and alterations in vitamin D metabolism occur on multiple fronts.
Vitamin D is diminished due to reduced skin production caused by hyperpigmentation, aging, sun avoidance, and dietary restrictions. Losses are increased in cases of proteinuria, where vitamin D-binding protein, albumin, and associated vitamin D metabolites are excreted in urine. Additionally, the hepatic conversion of vitamin D to 25(OH)D is reported to be suppressed in CKD patients. Consequently, the dose-response appears lower than in healthy individuals, although this is poorly understood. The decline in functional kidney tissue reduces the ability to convert 25 (OH)D to 1,25 (OH)2D (calcitriol), leading to lower plasma levels of 1,25 (OH)2D. The kidney's ability to internalize 25(OH)D may also be compromised, decreasing availability. In healthy individuals, plasma 25(OH)D levels between 15 and 40 nmol/L are sufficient to avoid substrate limitation for renal 1,25(OH)2D production. However, people with CKD may require higher concentrations.
What Is the Link between Vitamin D and Kidney Damage?
Vitamin D levels in various populations, including 60 percent of older and younger individuals in North America, are suboptimal due to inadequate outdoor activity, urbanization, air pollution, demographic shifts, and decreased skin production of vitamin D with age. Reports vary on vitamin D status across different countries.
Clinical studies on patients with kidney disease have shown abnormal mineral metabolism in early chronic kidney disease (CKD). In these patients, the active form of vitamin D is higher than the glomerular filtration rate (GFR). There is an inverse relationship between vitamin D levels and parathyroid hormone (PTH), serum phosphate, fibroblast growth factor 23 (FGF-23), and GFR. A recent population-based study found a significant association between PTH, vitamin D, and CKD.
In CKD, the expression of renal 1α-hydroxylase is inhibited to compensate for phosphate retention, leading to increased 24-hydroxylase expression, which degrades vitamin D. Dialysis patients have lower vitamin D levels than healthy individuals, and this adverse mechanism contributes to vitamin D deficiency in kidney disease patients. Kidney dysfunction, joint in these patients impairs vitamin D production, causing hypocalcemia and secondary hyperparathyroidism (HPT), which can lead to secondary osteoporosis. Vitamin D deficiency becomes more severe as kidney disease progresses. Due to the inverse correlation between vitamin D status and CKD progression, guidelines recommend maintaining vitamin D levels at 30 ng/mL or higher.
Conclusion
There are significant gaps in the evidence regarding managing vitamin D status in CKD-MBD, particularly concerning the dose-response relationship, secondary hyperparathyroidism (SHPT), altered bone metabolism, bone density and integrity, and fracture risk. The recent studies included in this systematic review showed considerable variability in their design and the forms of vitamin D used, with significant heterogeneity in duration, dosage, and population characteristics.
Our systematic review found that the impact of vitamin D on PTH concentrations was inconsistent across studies, and meta-analyses revealed a non-significant reduction. This contrasts with findings from studies on patients without pre-existing CKD. The likely explanation for this discrepancy is the small sample size of the studies and the presence of other dominant factors in some CKD patients that inhibit the reduction of PTH secretion.
