Journal Mobile Options
Table of Contents
Vol. 110, No. 1, 2008
Issue release date: September 2008
Nephron Clin Pract 2008;110:c58

Evidence for Persistent Vitamin D 1-Alpha-Hydroxylation in Hemodialysis Patients: Evolution of Serum 1,25-Dihydroxycholecalciferol after 6 Months of 25-Hydroxycholecalciferol Treatment

Jean G. · Terrat J.C. · Vanel T. · Hurot J.M. · Lorriaux C. · Mayor B. · Chazot C.
Centre de Rein Artificiel, Tassin, France

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: End-stage renal disease (ESRD) patients are thought to have impaired 1-α-hydroxylase capacity, but an extrarenal source of 1,25(OH)2D has been recognized. Objective: The aim of this study was to assess the evolution of serum 1,25(OH)2D in hemodialysis (HD) patients with vitamin D deficiency after 6 months of 25(OH)D3 supplementation, and to identify the factors associated with persistent 1,25(OH)2D production. Methods: HD patients in a HD center with vitamin D deficiency (i.e. 25(OH)D <75 nmol/l) who were not receiving any vitamin D derivatives or calcimimetics were studied. Patients who had previously undergone parathyroidectomy or nephrectomy or those with uncontrolled hypercalcemia or hyperphosphatemia were excluded from this study. The patients were administrated a dose of 10–30 µg/day of oral 25(OH)D3 based on the severity of their deficiency. The serum levels of 25(OH)D and 1,25(OH)2D evolution after 6 months were recorded. Responders were defined as patients with an increase in serum 1,25(OH)2D levels greater than the median value. Changes in mineral metabolism parameters were compared with those in the nonresponders. Results: Of the 253 patients, 225 (89%) were vitamin D-deficient, and 43 met the inclusion criteria. The patients were 72.6 ± 10 years old and had been on dialysis for 71 ± 70 months; 39% of the patients were female and 45% were diabetics. From baseline to 6 months of treatment, serum 25(OH)D levels increased from 27.8 ± 18 to 118 ± 34 nmol/l (p < 0.001) and serum 1,25(OH)2D levels increased from 7.7 ± 5 to 30.5 ± 15 pmol/l (p < 0.001) with a median increase of 20 pmol/l. The mean serum calcium level increased from 2.19 ± 0.1 to 2.25 ± 0.1 mmol/l (p = 0.009), the intact parathyroid hormone (iPTH) level decreased from 144 ± 108 to 108 ± 63 pg/ml (p = 0.05), and the bone alkaline phosphatase (BALP) level remained unchanged. The serum phosphate level increased slightly from 1.22 ± 0.3 to 1.34 ± 0.2 mmol/l (p = 0.04) with reduced hypophosphatemia. Compared with the responders (n = 24), most of the nonresponders (n = 19) were diabetic (63 vs. 29%, p = 0.02) and had a lesser increase of their 25(OH)D serum level. The serum level of FGF-23 was not significant. A positive correlation was observed between serum 1,25(OH)2D and serum 25(OH)D levels after 6 months of 25(OH)D3 treatment (p = 0.02). Conclusion: The Kidney Disease Outcomes Quality Improvement (KDOQI) guidelines do not recommend checking and treating vitamin D deficiency in chronic kidney disease (CKD) stage 5 patients due to the supposed lack of 1,25(OH)2D production. These data confirm persistent renal or extra-renal production of 1,25(OH)2D in HD patients after 6 months of 25(OH)D3 administration. Diabetes is the main factor associated with impaired 1,25(OH)2D production. 25(OH)D3 administration corrects vitamin D deficiency with few effects on mineral metabolism and stability of bone turnover markers.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Holick MF: Vitamin D deficiency. N Engl J Med 2007;357:266–281.
  2. Taskapan H, Ersoy FF, Passadakis PS, Tam P, Memmos DE, Katopodis KP, Ozener C, Akcicek F, Camsari T, Ates K, Ataman R, Vlachojannis JG, Dombros NA, Utas C, Akpolat T, Bozfakioglu S, Wu G, Karayaylali I, Arinsoy T, Stathakis CP, Yavuz M, Tsakiris DJ, Dimitriades AD, Yilmaz ME, Gultekin M, Oreopoulos DG: Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis. Clin Nephrol 2006;66:247–255.
  3. Saab G, Young DO, Gincherman Y, Giles K, Norwood K, Coyne DW: Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients. Nephron Clin Pract 2007;105:c132–c138.
  4. Del Valle E, Negri AL, Aguirre C, Fradinger E, Zanchetta JR: Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis. Hemodialysis Int 2007;11:315–321.
  5. Eknoyan G, Levin A, Levin NW: Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:1–201.
  6. Lambert PW, Stern PH, Avioli RC, Brackett NC, Turner RT, Greene A, Fu IY, Bell NH: Evidence for extrarenal production of 1 alpha,25-dihydroxyvitamin D in man. J Clin Invest 1982;69:722–725.
  7. Dusso A, Lopez-Hilker S, Rapp N, Slatopolsky E: Extra-renal production of calcitriol in chronic renal failure. Kidney Int 1988;34:368–375.
  8. Dusso AS, Finch J, Brown A, Ritter C, Delmez J, Schreiner G, Slatopolsky E: Extrarenal production of calcitriol in normal and uremic humans. J Clin Endocrinol Metab 1991;72:157–164.
  9. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T: Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004;113:561–568.
  10. Weber TJ, Liu S, Indridason OS, Quarles LD: Serum FGF23 levels in normal and disordered phosphorus homeostasis. J Bone Miner Res 2003;18:1227–1234.
  11. Fukagawa M, Fukuda N, Yi H, Kurokawa K: Resistance of parathyroid cell to calcitriol as a cause of parathyroid hyperfunction in chronic renal failure. Nephrol Dial Transplant 1995;10:316–319.
  12. Patel SR, Ke HQ, Vanholder R, Koenig RJ, Hsu CH: Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins. J Clin Invest 1995;96:50–59.
  13. Korkor AB: Reduced binding of 1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 1987;316:1573–1577.
  14. Rodriguez M, Caravaca F, Fernandez E, Borrego MJ, Lorenzo V, Cubero J, Martin-Malo A, Betriu A, Rodriguez AP, Felsenfeld AJ: Evidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism. J Bone Miner Res 1997;12:347–355.
  15. LaClair RE, Hellman RN, Karp SL, Kraus M, Ofner S, Li Q, Graves KL, Moe SM: Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States. Am J Kidney Dis 2005;45:1026–1033.
  16. Khan S: Vitamin D deficiency and secondary hyperparathyroidism among patients with chronic kidney disease. Am J Med Sci 2007;333:201–207.
  17. Chang JM, Lin SP, Kuo HT, Tsai JC, Tomino Y, Lai YH, Chen HC: 7–84 parathyroid hormone fragments are proportionally increased with the severity of uremic hyperparathyroidism. Clin Nephrol 2005;63:351–355.
  18. Glendenning P, Taranto M, Noble JM, Musk AA, Hammond C, Goldswain PR, Fraser WD, Vasikaran SD: Current assays overestimate 25-hydroxyvitamin D3 and underestimate 25-hydroxyvitamin D2 compared with HPLC: need for assay-specific decision limits and metabolite-specific assays. Ann Clin Biochem 2006;43:23–30.
  19. Martinez I, Saracho R, Montenegro J, Llach F: A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism. Nephrol Dial Transplant 1996;11(suppl 3):22–28.

    External Resources

  20. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL: Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71:31–38.
  21. Feldman D, Pike W Jr, Glorieux, FH: Vitamin D. Elsevier Academic Press, 2005.
  22. Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T, Ono K, Kakitani M, Tomizuka K, Fujita T, Fukumoto S, Yamashita T: Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol 2005;289:F1088–F1095.
  23. Barthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper HAT, Hsieh JC, Slater SA, Hsieh G, Kaczmarska M, Jurutka PW, Kolek OI, Ghishan FK, Haussler MR: 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Molec Biol 2007;103:381–388.
  24. Sato T: Renal bioactivation of vitamin D and its key modulators. Clin Calcium 2007;17:686–690.
  25. Elder GJ: Vitamin D levels, bone turnover and bone mineral density show seasonal variation in patients with chronic kidney disease stage 5. Nephrology 2007;12:90–94.
  26. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS: Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777–783.
  27. Chiu KC, Chu A, Go VL, Saad MF: Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004;79:820–825.
  28. Sanchez CM, Bajo AM, Selgas R, Mate A, Millan I, Martinez EM, Lopez-Barea F: Parathormone secretion in peritoneal dialysis patients with adynamic bone disease. Am J Kidney Dis 2000;36:953–961.
  29. Malluche HH, Monier-Faugere MC: Risk of adynamic bone disease in dialyzed patients. Kidney Int Suppl 1992;38:S62–S67.
  30. Halloran BP, Schaefer P, Lifschitz M, Levens M, Goldsmith RS: Plasma vitamin D metabolite concentrations in chronic renal failure: effect of oral administration of 25-hydroxyvitamin D3. J Clin Endocrinol Metab 1984;59:1063–1069.
  31. Hewison M, Zehnder D, Bland R, Stewart PM: 1Alpha-hydroxylase and the action of vitamin D. J Mol Endocrinol 2000;25:141–148.
  32. Dusso A, Lopez-Hilker S, Lewis-Finch J, Grooms P, Brown A, Martin K, Slatopolsky E: Metabolic clearance rate and production rate of calcitriol in uremia. Kidney Int 1989;35:860–864.
  33. Dusso A, Finch J, Delmez J, Rapp N, Lopez-Hilker S, Brown A, Slatopolsky E: Extrarenal production of calcitriol. Kidney Int Suppl 1990;29:S36–S40.
  34. Holick MF: Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 2004;80:1678S–1688S.
  35. Jones G: Expanding role for vitamin D in chronic kidney disease: Importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3). Semin Dial 2007;20:316–324.
  36. Monge M, Shahapuni I, Oprisiu R, El Esper N, Moriniere P, Massy Z, Choukroun G, Fournier A: Reappraisal of 2003 NKF-K/DOQI guidelines for management of hyperparathyroidism in chronic kidney disease patients. Nat Clin Pract 2006;2:326–336.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50