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Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis.
Clin Nutr. 2018 06; 37(3):1041-1045.CN

Abstract

BACKGROUND & AIMS

While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D2 and Vitamin D3 is becoming increasingly common in these patients, little is known about 24,25(OH)2D3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH)2D3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH)2D3 levels from three controlled trials of Vitamin D2 and Vitamin D3 supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis.

METHODS

680 samples from three controlled trials of Vitamin D2 or Vitamin D3 supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D3, or 50,000 IU Vitamin D2, or weekly doses of 10,000 IU or 20,000 IU Vitamin D3. Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH)2D3 levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time.

RESULTS

The subjects given Vitamin D3 had significant increases in 25(OH)D levels. Serum 24,25(OH)2D3 levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH)2D3 in healthy populations.

CONCLUSIONS

We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012.

Authors+Show Affiliations

Department of Diabetes, Endocrinology & Metabolism, University of Nebraska Medical Center, 984130 Nebraska Medical Center, Omaha, NE, 68198-4130, USA. Electronic address: laura.armas@unmc.edu.Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L3N6, Canada. Electronic address: martin.kaufmann@queensu.ca.Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, 984375 Nebraska Medical Center, Omaha, NE, 68198-4375, USA. Electronic address: elyden@unmc.edu.Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L3N6, Canada. Electronic address: gj1@queensu.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28506446

Citation

Graeff-Armas, Laura A., et al. "Serum 24,25-dihydroxyvitamin D3 Response to Native Vitamin D2 and D3 Supplementation in Patients With Chronic Kidney Disease On Hemodialysis." Clinical Nutrition (Edinburgh, Scotland), vol. 37, no. 3, 2018, pp. 1041-1045.
Graeff-Armas LA, Kaufmann M, Lyden E, et al. Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis. Clin Nutr. 2018;37(3):1041-1045.
Graeff-Armas, L. A., Kaufmann, M., Lyden, E., & Jones, G. (2018). Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis. Clinical Nutrition (Edinburgh, Scotland), 37(3), 1041-1045. https://doi.org/10.1016/j.clnu.2017.04.020
Graeff-Armas LA, et al. Serum 24,25-dihydroxyvitamin D3 Response to Native Vitamin D2 and D3 Supplementation in Patients With Chronic Kidney Disease On Hemodialysis. Clin Nutr. 2018;37(3):1041-1045. PubMed PMID: 28506446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis. AU - Graeff-Armas,Laura A, AU - Kaufmann,Martin, AU - Lyden,Elizabeth, AU - Jones,Glenville, Y1 - 2017/04/30/ PY - 2016/10/13/received PY - 2017/04/04/revised PY - 2017/04/24/accepted PY - 2017/5/17/pubmed PY - 2019/10/1/medline PY - 2017/5/17/entrez KW - 24,25-Dihydroxyvitamin D(3) KW - Chronic renal disease KW - Drug metabolism KW - Hemodialysis KW - Vitamin D SP - 1041 EP - 1045 JF - Clinical nutrition (Edinburgh, Scotland) JO - Clin Nutr VL - 37 IS - 3 N2 - BACKGROUND & AIMS: While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D2 and Vitamin D3 is becoming increasingly common in these patients, little is known about 24,25(OH)2D3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH)2D3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH)2D3 levels from three controlled trials of Vitamin D2 and Vitamin D3 supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis. METHODS: 680 samples from three controlled trials of Vitamin D2 or Vitamin D3 supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D3, or 50,000 IU Vitamin D2, or weekly doses of 10,000 IU or 20,000 IU Vitamin D3. Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH)2D3 levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time. RESULTS: The subjects given Vitamin D3 had significant increases in 25(OH)D levels. Serum 24,25(OH)2D3 levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH)2D3 in healthy populations. CONCLUSIONS: We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012. SN - 1532-1983 UR - https://www.unboundmedicine.com/medline/citation/28506446/Serum_2425_dihydroxyvitamin_D3_response_to_native_vitamin_D2_and_D3_Supplementation_in_patients_with_chronic_kidney_disease_on_hemodialysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0261-5614(17)30159-0 DB - PRIME DP - Unbound Medicine ER -