Review ArticleVitamin D and Kidney Stones
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
References (53)
- et al.
Prevalence of kidney stones in the United States
Eur Urol
(2012) - et al.
New insights into the pathogenesis of idiopathic hypercalciuria
Semin Nephrol
(2008) - et al.
Increasing requests for vitamin D measurement: costly, confusing, and without credibility
Lancet
(2012) - et al.
Prevalence and metabolic abnormalities of vitamin D–inadequate patients presenting with urolithiasis to a tertiary stone clinic
Urology
(2012) - et al.
Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis
Am J Clin Nutr
(1994) - et al.
Personalized intervention in monogenic stone formers
J Urol
(2018) - et al.
Stone formation in genetic hypercalciuric rats
Kidney Int
(1995) - et al.
Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats
Kidney Int
(2002) - et al.
Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial
Am J Clin Nutr
(2019) - et al.
Vitamin D status and ill health: a systematic review
Lancet Diabetes Endocrinol
(2014)
Nephrolithiasis and risk of incident bone fracture
J Urol
Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions
J Urol
A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones
N Engl J Med
Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey
J Bone Miner Res
Mutations in CYP24A1 and idiopathic infantile hypercalcemia
N Engl J Med
Calcium and phosphorus regulatory hormones and risk of incident symptomatic kidney stones
Clin J Am Soc Nephrol
Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria
J Clin Endocrinol Metab
Vitamin D receptor gene (VDR) polymorphisms and the urolithiasis risk: an updated meta-analysis based on 20 case–control studies
Urolithiasis
Calcium-sensing receptor and calcium kidney stones
Jf Transl Med
A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1
PLoS Genet
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Vitamin D and kidney stones
2023, Feldman and Pike's Vitamin D: Volume Two: Disease and Therapeutics1,25-dihydroxyvitamin D and cardiometabolic risk in healthy sedentary adults: The FIT-AGEING study
2021, International Journal of CardiologyCitation 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]).
Mechanistic approach to herbal formulations used for urolithiasis treatment
2020, Obesity Medicine
Conflict of Interest: Dr. Schulster: None; Dr. Goldfarb: Consultant: Allena, Alnylam, AstraZeneca, Retrophin; Owner, Dr. Arnie's Inc.; Research: Dicerna.