The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

Turner, Mandy E; Rowsell, Tyler S; White, Christine; Kaufmann, Martin; Norman, Patrick; Neville, Kathryn; Petkovich, Martin; Jones, Glenville; Adams, Michael; Holden, Rachel M.

doi:10.1038/s41598-022-15033-9

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…the animal. Later in vitro studies by Inouye and Sakaki (26) and Tang et al (27) explored the catalytic properties of the 1-hydroxylase enzyme and confirmed that 1,24,25-(OH) 3 (29) It should be noted that the renewed interest in the catabolite 1,24,25-(OH) 3 D 3 is not confined to its role in bone metabolism but is also implicated in the dysfunctional metabolism in chronic kidney disease (30,31) as well as in normal neonatal calcium homeostasis and skeletal development. (32) Although 1,25-(OH) 2 D 3 is considered the active form of vitamin D, the other metabolites measured in this study possess VDR binding capabilities and actions.…”

Section: Discussionmentioning

confidence: 96%

“…( 28 ) In support of the possibility that circulating 1,24,25‐(OH) 3 D 3 could be derived from CYP27B1 hydroxylation of high levels of circulating 24,25‐(OH) 2 D 3 , Martineau et al demonstrated increased 1,24,25‐(OH) 3 D 3 (without an increase in 1,25‐[OH] 2 D 3 ) in response to pharmacological doses of 24,25‐(OH) 2 D 3 given to mice undergoing bone fracture repair. ( 29 ) It should be noted that the renewed interest in the catabolite 1,24,25‐(OH) 3 D 3 is not confined to its role in bone metabolism but is also implicated in the dysfunctional metabolism in chronic kidney disease ( 30,31 ) as well as in normal neonatal calcium homeostasis and skeletal development. ( 32 )…”

Section: Discussionmentioning

confidence: 99%

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Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Burt

Kaufmann

Rose

et al. 2023

J of Bone & Mineral Res

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In a 36‐month randomized controlled trial examining the effect of high‐dose vitamin D3 on radial and tibial total bone mineral density (TtBMD), measured by high‐resolution peripheral quantitative tomography (HR‐pQCT), participants (311 healthy males and females aged 55–70 years with dual‐energy X‐ray absorptiometry T‐scores > −2.5 without vitamin D deficiency) were randomized to receive 400 IU (N = 109), 4000 IU (N = 100), or 10,000 IU (N = 102) daily. Participants had HR‐pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36 months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25‐(OH)D3; 24,25‐(OH)2D3; 1,25‐(OH)2D3; and 1,24,25‐(OH)3D3]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36 months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25‐(OH)D3, 24,25‐(OH)2D3 and 1,24,25‐(OH)3D3, but no dose‐related change in plasma 1,25‐(OH)2D3 was observed. There was a significant negative slope for radius TtBMD and 1,24,25‐(OH)3D3 (−0.05, 95% confidence interval [CI] −0.08, −0.03, p < 0.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25‐(OH)D3 (female: −0.01, 95% CI −0.12, −0.07; male: −0.04, 95% CI −0.06, −0.01, p = 0.001) and 24,25‐(OH)2D3 (female: −0.75, 95% CI −0.98, −0.52; male: −0.35, 95% CI −0.59, −0.11, p < 0.001). For the tibia there was a significant negative slope for 25‐(OH)D3 (−0.03, 95% CI −0.05, −0.01, p < 0.001), 24,25‐(OH)2D3 (−0.30, 95% CI −0.44, −0.16, p < 0.001), and 1,24,25‐(OH)3D3 (−0.03, 95% CI −0.05, −0.01, p = 0.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25‐(OH)2D3 may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25‐(OH)2D3 did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25‐(OH)3D3 prevented the detection of a dose‐related rise in plasma 1,25‐(OH)2D3. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Burt

Kaufmann

Rose

et al. 2023

J of Bone & Mineral Res

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“…A reduction in CYP27B1 activity occurs in kidney disease, which subsequently inhibits the production of 1,25(OH) 2 D 3 and impairs the reabsorption of 25(OH)D [ 1 ]. A significant decrease in 1,25(OH) 2 D 3 levels is observed when the GFR is 40 mL/min or less [ 33 , 34 ]. The decrease in CYP27B1 enzyme activity and 1,25(OH) 2 D 3 levels can be explained by the increase in FGF-23 activity observed in the early stages of kidney disease [ 35 , 36 ].…”

Section: Vitamin D Signaling Pathway In Diabetic Kidney Diseasementioning

confidence: 99%

Vitamin D and Diabetic Kidney Disease

Huang

Lin

Hong

et al. 2023

IJMS

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Vitamin D is a hormone involved in many physiological processes. Its active form, 1,25(OH)2D3, modulates serum calcium–phosphate homeostasis and skeletal homeostasis. A growing body of evidence has demonstrated the renoprotective effects of vitamin D. Vitamin D modulates endothelial function, is associated with podocyte preservation, regulates the renin–angiotensin–aldosterone system, and has anti-inflammatory effects. Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease worldwide. There are numerous studies supporting vitamin D as a renoprotector, potentially delaying the onset of DKD. This review summarizes the findings of current research on vitamin D and its role in DKD.

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“…Furthermore, the goal should not be complete normalization of iPTH levels. New developments, such as extended-release formulations [ 109 , 110 ] (which correct both vitamin D deficiency and are more effective than native in decreasing iPTH levels) and new analogs, biomarkers, molecular targets, and even renal pathologies [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ], may then help us better define optimal VD and iPTH levels or the best formulation at different CKD stages [ 92 , 107 , 109 ], thereby directing us towards an improved, personalized medicine. It is possible that the approaches that we took to correct VD deficiency are at least partially wrong and that current interventions with native and/or active VD were not properly targeted at more effective goals.…”

Section: Kdigo Guidelines: Secondary Hyperparathyroidism and Active V...mentioning

confidence: 99%

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines

et al. 2023

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Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

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The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

Cited by 7 publications

References 26 publications

Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Vitamin D and Diabetic Kidney Disease

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines

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