Date of publication: May 30, 2017

News & Views

The Role of 25 Hydroxyvitamin D in MBD: What is the Right Target Level?

Vitamin D is an integral and vital part of the complex management of calcium, phosphate and parathyroid hormone homeostasis.[1] In patients with chronic kidney disease (CKD) vitamin D insufficiency (25 hydroxyvitamin D (25(OH)D) < 30ng/mL) is extremely common and is estimated to affect 71–83% of patients with stage 3 or 4 CKD.[2,3]

The effectiveness of vitamin D treatment for secondary hyperparathyroidism (SHPT), an early indicator of MBD in CKD, is well known. Hormone replacement therapy with ‘active’ or ‘vitamin D receptor activator’ (VDRA) compounds are effective in correcting parathyroid hormone levels (PTH), as they directly target the vitamin D receptor. However, the recently observed lack of cardiovascular benefits but increased risk of hypercalcaemia in the OPERA and PRIMO trials highlights the need for careful risk/benefit assessment when using calcitriol or other VDRAs in pre-dialysis patients.[4,5]

When increased PTH levels are first detected, KDIGO treatment guidelines recommend the same vitamin D replacement strategies as those used for the general population, although it is recognized that this guidance was opinion based on the limited trials available.[6]

The evidence that replacement therapy with nutritional vitamin D supplements lowers PTH is mixed, particularly in pre-dialysis patients.[7] Such nutritional vitamin D supplements include ergocalciferol and cholecalciferol.

It also remains debatable whether the hydroxyvitamin D levels recommended for the general population are adequate for early correction of PTH levels in CKD settings. A target for 25(OH)D of >30ng/mL is suggested by the KDOQI 2003 guidelines, although some analysts have used a value of <20ng/mL to define deficiency.[1],[8] Other questions that remain include:

  • whether continued vitamin D therapy results in continued impact on SHPT, and
  • at what point do increased vitamin D levels begin to lead to hypercalcemia or hyperphosphataemia?

In an effort to shed light on these uncertainties one study has found evidence for an optimal level of 25(OH)D.[9] Data from over 14,000 patients showed a significant inverse relationship between PTH and 25(OH)D, which plateaued at between 42-48ng/mL in all 5 stages of CKD.[9] Importantly, the authors also found no association between the higher 25(OH)D levels and either hyperphosphataemia or hypercalcemia.[9]The potential importance of higher 25(OH)D levels is supported by the results of two studies in stage 3–4 CKD, in which correction of 25(OH)D levels above 30 ng/mL was also associated with a significant lowering of PTH levels.[2]

While the data for nutritional vitamin D supplements is not definitive, and the use of hormone replacement therapy with active vitamin D may be revised in the future, current approaches to the management of vitamin D insufficiency may need to be revisited in pre-dialysis patients.

References:

  1. Goldsmith DJA. Pro: Should we correct Vitamin D deficiency/insufficiency in chronic kidney disease patients with inactive forms of Vitamin D or just treat them with active Vitamin D forms? Nephrol Dial Transplant. 2016;31(5):698-705. doi:10.1093/ndt/gfw082.
  2. Sprague SM, Crawford PW, Melnick JZ, et al. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. Am J Nephrol. 2016;44(4):316-325. doi:10.1159/000450766.
  3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. doi:10.1210/jc.2011-0385.
  4. Thadhani R, Wenger J, Tamez H, et al. Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease. 2012;307(7):674-684.
  5. Wang AY-M, Fang F, Chan J, et al. Effect of paricalcitol on left ventricular mass and function in CKD–the OPERA trial. J Am Soc Nephrol. 2014;25(1):175-86. doi:10.1681/ASN.2013010103.
  6. KDIGO. KDIGO Clinical Practice Guideline for the diagnosis, evaluation, prevention and treatment of CKD-MBD. Kidney Int. 2009;76(August):Supplement 113.
  7. Agarwal R, Georgianos PI. Con: Nutritional Vitamin D replacement in chronic kidney disease and end-stage renal disease. Nephrol Dial Transplant. 2016;31(5):706-713. doi:10.1093/ndt/gfw080.
  8. Eknoyan G, Levin A, Levin NW. Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4):1-201. doi:10.1016/S0272-6386(03)00905-3.
  9. Ennis JL, Worcester EM, Coe FL, Sprague SM. Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. J Nephrol. 2016;29(1):63-70. doi:10.1007/s40620-015-0186-0.

 

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