Elsevier

Urology

Volume 139, May 2020, Pages 1-7
Urology

Review Article
Vitamin D and Kidney Stones

https://doi.org/10.1016/j.urology.2020.01.030Get rights and content

This review explores the relationship between vitamin D supplementation and lithogenesis. A causal relationship has been assumed despite myriad studies demonstrating that therapeutic doses of vitamin D do not increase lithogenic risk. Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations. Additionally, the evidence for who is vitamin D deficient, and the benefits of supplementation in those not at risk for rickets, is sparse. Concerns may be avoidable as vitamin D screening appears unnecessary in most patients, and superior pharmacology is available which increases bone density, while decreasing stone formation.

Section snippets

GENESIS OF CALCIUM KIDNEY STONES

Calcium stone formation is a complex physiological process, extensively investigated with multiple purported mechanistic models, the details of which are beyond the scope of this review. While much is still unknown, the broad prerequisites for stone formation are higher supersaturation, crystallization, growth, and aggregation. The complex chemical properties of urine such as pH, poly-ionic content, concentrations of promoters, and inhibitors all contribute. A common urinary abnormality in

VITAMIN D METABOLISM

Vitamin D is a fat-soluble vitamin, inactive in its natural form and obtained largely and efficiently from sunlight-stimulated synthesis in the skin, and less so from diet. Vitamin D undergoes hydroxylation in the liver by 25-hydroxylase (CYP2PR1) resulting in 25-hydroxyvitamin D3. Subsequent hydroxylation, largely in the kidney, by 1α-hydroxylase (CYP27B1) results in the production of the bioactive form 1,25-dihydroxyvitamin D3 (calcitriol). Calcitriol binds to intracellular receptors in

GENETIC VARIATIONS IN VITAMIN D METABOLISM IN STONE FORMERS

Various mechanisms have been proposed to answer this question, with recent evidence suggests the answer may be related to mutations in CYP24A1, creating an inability to deactivate calcitriol (Fig. 1), as evidenced in idiopathic infantile hypercalcemia.10 Schlingmann et al demonstrated that in children with idiopathic infantile hypercalcemia, significant nephrocalcinosis and hypercalcemia were seen in the setting of suppressed serum PTH and markedly elevated 1,25-dihydroxyvitamin D3 due to

VITAMIN D SUPPLEMENTATION AND KIDNEY STONE RISK

In the largest study to date on vitamin D and kidney stones, 3 well-characterized cohorts were studied: men in the Health Professionals Follow-up Study and women in the Nurses’ Health Studies I and II.6 In nearly 200,000 men and women with long-term prospective follow-up, no association was found between vitamin D intake and risk of stones after multivariate adjustment. The Nurses’ Health Studies II group had a suggestion of higher risk with a P value of .02; however the confidence interval

IS VITAMIN D SUPPLEMENTATION NECESSARY?

Low levels of 25-(OH)D have been associated with a host of adverse events including fractures, falls, cardiovascular disease, colorectal cancer, diabetes, depression, cognitive decline, and death.32 Randomized trials of vitamin D supplementation have generally not supported these associations as causal in nature. With regards to bone health, meta-analysis looking at supplementation in asymptomatic vitamin D deficient populations found a reduction in the average number of falls but no reduction

TREATMENT OF REDUCED BMD IN STONE FORMERS

Symptomatic populations with nontraumatic fractures, liver or kidney dysfunction or malabsorptive diseases clearly will need intervention for bone health, and stone formers are no exception. Indeed, a history of kidney stones and higher urine calcium excretion predispose to lower BMD3 and are independently associated with a higher risk of wrist fracture in both men and women.40 Additionally, in patients presenting with urolithiasis, the prevalence of inadequate vitamin D levels was more than

CONCLUSION

Kidney stones have significant cost and quality of life implications. The prevalence in relation to obesity and diet is indisputable. Widespread screening for vitamin D leading to supplementation does not appear to have contributed to kidney stone risk in the general population at therapeutic doses. Elevated calcitriol in known stone formers does pose an increased lithogenic risk and vitamin D may increase stones in patients with CYP24A1 mutations. Genetic testing, while possibly useful for

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      Citation Excerpt :

      Concretely, an increased incidence of vitamin D deficiency has been described in elderly individuals with CVD [28]. However, excessive levels of vitamin D have been also associated with CVD-related problems [8] including hypercalcemia, hypercalciuria, and kidney stones, among others [28,33,53]. Several molecular and physiological pathways have been described as an explanation of the mechanistic basis of the influence of 1,25(OH)2D on cardiovascular function (P. E. [41]).

    Conflict of Interest: Dr. Schulster: None; Dr. Goldfarb: Consultant: Allena, Alnylam, AstraZeneca, Retrophin; Owner, Dr. Arnie's Inc.; Research: Dicerna.

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