The role of vitamin D levels in the development and progression of kidney disease: The current state of the problem. A review

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Abstract

Progressive loss of kidney function is associated with significant morbidity and mortality and is an important global health concern, given the high prevalence of chronic kidney disease (CKD). Recently, there has been an increased interest in finding new therapeutic strategies that may slow the progression of renal dysfunction. Numerous studies using various experimental models have proven that treatment with active metabolites of vitamin D can have a renoprotective effect, preventing fibrosis, apoptosis, and inflammation. In addition, vitamin D deficiency and insufficiency are common conditions in CKD patients in the pre-dialysis stages. It has been established that the vitamin D serum level is directly proportional to kidney function. Recent clinical studies have shown that reducing proteinuria and mortality in CKD patients receiving active vitamin D goes beyond the classical role of vitamin D in maintaining bone and mineral metabolism. Therefore, vitamin D analogs have the potential to become components of CKD treatment to achieve better clinical outcomes in patients with advanced kidney disease and those on hemodialysis. Current guidelines recommend treatment with vitamin D only in patients with moderate CKD with secondary hyperparathyroidism and vitamin D deficiency. This review presents the results of numerous studies demonstrating the prevalence of vitamin D deficiency among patients with various kidney diseases, the effect of vitamin D in reducing the rate of CKD progression, as well as the clinical outcomes of vitamin D use in patients with infectious and non-infectious kidney diseases.

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About the authors

Irina N. Zakharova

Russian Medical Academy of Continuous Professional Education

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0003-4200-4598

D. Sci. (Med.), Prof

 

Russian Federation, Moscow

Anna N. N. Kasyanova

Stavropol State Medical University; Regional Children's Clinical Hospital

Author for correspondence.
Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0002-9524-8724

Cand. Sci. (Med.)

Russian Federation, Stavropol; Stavropol

Leonid Ya. Klimov

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0001-7248-1614

D. Sci. (Med.), Prof., Stavropol State Medical University

 

Russian Federation, Stavropol

Svetlana V. Dolbnya

Stavropol State Medical University; Regional Children's Clinical Hospital

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0002-2056-153X

Cand. Sci. (Med.)

Russian Federation, Stavropol; Stavropol

Alena A. Karaikozova

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0001-8562-651X

Student, Stavropol State Medical University

Russian Federation, Stavropol

Artem K. Minasyan

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0001-7519-8646

Graduate Student

Russian Federation, Stavropol

Natalia A. Fedko

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0002-0311-4068

D. Sci. (Med.), Prof., Stavropol State Medical University

 

Russian Federation, Stavropol

Natalia V. Zaritovskaya

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0009-0009-9178-1634

D. Sci. (Med.), Assoc. Prof., Stavropol State Medical University

Russian Federation, Stavropol

Elena V. Popova

Stavropol State Medical University

Email: a.nicolaevnakasjanova@yandex.ru
ORCID iD: 0000-0003-4155-0896

Cand. Sci. (Med.), Stavropol State Medical University

Russian Federation, Stavropol

References

  1. Dybiec J, Szlagor M, Młynarska E, et al. Structural and functional changes in aging kidneys. Int J Mol Sci. 2022;23:15435. doi: 10.3390/ijms232315435
  2. Fularski P, Czarnik W, Frankenstein H, et al. Unveiling selected influences on chronic kidney disease development and progression. Cells. 2024;13:751. doi: 10.3390/cells13090751
  3. Игнатова М.С. Детская нефрология: Руководство для врачей. 3-е изд., перераб. и доп. М.: Медицинское информационное агентство, 2011 [Ignatova MS. Detskaia nefrologiia: Rukovodstvo dlia vrachei. 3-e izd., pererab. i dop. Moscow: Meditsinskoe informatsionnoe agentstvo, 2011 (in Russian)].
  4. Bikle DD, Feingold KR, Anawalt B, et al. Vitamin D: Production, Metabolism and Mechanisms of Action. 2021. In: Endotext. South Dartmouth (MA): MDText.com, Inc, 2000.
  5. Adamantidi T, Maris G, Altantsidou P, Tsoupras A. Anti-Inflammatory benefits of vitamin D and Its analogues against glomerulosclerosis and kidney diseases. Sclerosis. 2024;2:217-65. DOI:10.3390/ sclerosis2030015
  6. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062-72. doi: 10.1172/JCI29449
  7. Громова О.А., Торшин И.Ю. Витамин D – смена парадигмы. Под ред. акад. РАН Гусева Е.И., проф. Захаровой И.Н. М.: ТОРУС ПРЕСС, 2015 [Gromova OA, Torshin IYu. Vitamin D – smena paradigmy. Pod red. akad. RAN Guseva EI, prof. Zakharovoi IN. Moscow: TORUS PRESS, 2015 (in Russian)].
  8. Национальная программа «Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции». Союз педиатров России. М.: ПедиатрЪ, 2021 [Natsionalnaia programma “Nedostatochnost' vitamina D u detei i podrostkov Rossiiskoi Federatsii: sovremennyie podkhody k korrektsii”. Soiuz pediatrov Rossii. Moscow: Pediatr, 2021 (in Russian)].
  9. Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase. Mol Cell Endocrinol. 2004;215(1-2):31-8. doi: 10.1016/j.mce.2003.11.017
  10. Holick MF. Vitamin D: extraskeletal health. Rheum Dis Clin North Am. 2012;38(1):141-60. doi: 10.1016/j.rdc.2012.03.013
  11. Kim CS, Kim SW. Vitamin D and chronic kidney disease. Korean J Intern Med. 2014;29(4):416-27. doi: 10.3904/kjim.2014.29.4.416
  12. Ganimusa I, Chew E, Lu EMC. Vitamin D deficiency, chronic kidney disease and periodontitis. Medicina. 2024;60(3):420. doi: 10.3390/medicina60030420
  13. Wimalawansa SJ. Vitamin D Deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Biology. 2019;8(2):30. doi: 10.3390/biology8020030
  14. Souza CS, Deluque AL, Oliveira BM, et al. Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions. Nutr Diabetes. 2023;13(1):9. doi: 10.1038/s41387-023-00238-2
  15. Wu W, Li X, Di J, et al. Dietary inflammatory index is associated with vitamin D in CKD patients. Int Urol Nephrol. 2024;56:335-44. doi: 10.1007/s11255-023-03679-x
  16. Hilpert J, Wogensen L, Thykjaer T, et al. Expression prof iling conf irms the role of endocytic receptor megalin in renal vitamin D3 metabolism. Kidney Int. 2002;62(5):1672-81. doi: 10.1046/j.1523-1755.2002.00634.x
  17. Leheste JR, Rolinski B, Vorum H, et al. Megalin knockout mice as an animal model of low molecular weight proteinuria. Am J Pathol. 1999;155(4):1361-70. doi: 10.1016/S0002-9440(10)65238-8
  18. Liu W, Yu WR, Carling T, et al. Regulation of gp330/megalin expression by vitamins A and D. Eur J Clin Invest. 1998;28(2):100-7. doi: 10.1046/j.1365-2362.1998.00253.x
  19. Perwad F, Azam N, Zhang MY, et al. Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology. 2005;146(12):5358-64. doi: 10.1210/en.2005-0777
  20. Perwad F, Zhang MYH, Tenenhouse HS, Portale AA. Fibroblast frowth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Ren Physiol. 2007;293(5):F1577-83. doi: 10.1152/ajprenal.00463.2006
  21. Imanishi Y, Inaba M, Nakatsuka K, et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int. 2004;65(5):1943-6. doi: 10.1111/j.1523-1755.2004.00604.x
  22. Larsson T, Nisbeth U, Ljunggren O, et al. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003;64(6):2272-9. doi: 10.1046/j.1523-1755.2003.00328.x
  23. Zand L, Kumar R. The use of vitamin D metabolites and analogs in the treatment of chronic kidney disease. Endocrinol Metab Clin N Am. 2017;46(4):983-1007. doi: 10.1016/j.ecl.2017.07.008
  24. Kuro-o M. Klotho and the aging process. Korean J Intern Med. 2011;26(2):113-22. doi: 10.3904/kjim.2011.26.2.113
  25. Negrea L. Active vitamin D in chronic kidney disease: getting right back where we started from? Kidney Dis. 2018;5(2):59-68. doi: 10.1159/000495138
  26. Dusso AS, Tokumoto M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int. 2011;79(7):715-29. doi: 10.1038/ki.2010.543
  27. Jacob AI, Sallman A, Santiz Z, Hollis BW. Defective photoproduction of cholecalciferol in normal and uremic humans. J Nutr. 1984;114(7):1313-9. doi: 10.1093/jn/114.7.1313
  28. Ye JJ, Zhou TB, Zhang YF, et al. Levels of vitamin D receptor and CYP24A1 in patients with end-stage renal disease. Afr Health Sci. 2016;16(2):462-7. doi: 10.4314/ahs.v16i2.14
  29. Захарова И.Н., Мальцев С.В., Заплатников А.Л., и др. Влияние витамина D на иммунный ответ организма. Педиатрия. Consilium Medicum. 2020;2:29-37 [Zakharova IN, Maltsev SV, Zaplatnikov AL, et al. Influence of vitamin D on the immune response of the organism. Pediatrics. Consilium Medicum. 2020;2:29-37 (in Russian)]. doi: 10.26442/26586630.2020.2.200238
  30. Захарова И.Н., Климов Л.Я., Касьянова А.Н., и др. Современные представления об иммунотропных эффектах витамина D. Вопросы практической педиатрии. 2019;14(1):7-17 [Zakharova IN, Klimov LYa, Kasyanova AN, et al. Modern conception about vitamin D immunotropic effects. Clinical Practice in Pediatrics. 2019;14(1):7-17 (in Russian)]. doi: 10.20953/1817-7646-2019-1-7-17
  31. Rapa SF, Di Iorio BR, Campiglia P, et al. Inflammation and oxidative stress in chronic kidney disease – potential therapeutic role of minerals, vitamins and plant-derived metabolites. Int J Mol Sci. 2020;21(1):263. doi: 10.3390/ijms21010263
  32. Mihai S, Codrici E, Popescu ID, et al. Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome. J Immunol Res. 2018:2180373. doi: 10.1155/2018/2180373
  33. Sanchez-Nino MD, Bozic M, Cordoba-Lanus E, et al. Beyond proteinuria: VDR activation reduces renal inflammation in experimental diabetic nephropathy. Am J Physiol Renal Physiol. 2012;302:F647-57. doi: 10.1152/ajprenal.00090.2011
  34. Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. J Am Soc Nephrol. 2008;19(9):1741-52. doi: 10.1681/ASN.2007060666
  35. Deb DK, Sun T, Wong KE, et al. Combined vitamin D analog and AT1 receptor antagonist synergistically block the development of kidney disease in a model of type 2 diabetes. Kidney Int. 2010;77:1000-9. doi: 10.1038/ki.2010.22
  36. Park JW, Bae EH, Kim IJ, et al. Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats. Am J Physiol Renal Physiol. 2010;298:F301-13. doi: 10.1152/ajprenal.00471.2009
  37. He W, Kang YS, Dai C, Liu Y. Blockade of Wnt/beta-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. J Am Soc Nephrol. 2011;22:90-103. doi: 10.1681/ASN.2009121236
  38. Schwarz U, Amann K, Orth SR, et al. Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats. Kidney Int. 1998;53(6):1696-705. doi: 10.1046/j.1523-1755.1998.00951.x
  39. Park JW, Bae EH, Kim IJ, et al. Paricalcitol attenuates cyclosporine-induced kidney injury in rats. Kidney Int. 2010;77(12):1076-85. doi: 10.1038/ki.2010.69
  40. Park JW, Cho JW, Joo SY, et al. Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation. Eur J Pharmacol. 2012;683(1-3):301-9. doi: 10.1016/j.ejphar.2012.03.019
  41. Xiao H, Shi W, Liu S, et al. 1,25-Dihydroxyvitamin D(3) prevents puromycin aminonucleoside-induced apoptosis of glomerular podocytes by activating the phosphatidylinositol 3-kinase/Akt-signaling pathway. Am J Nephrol. 2009;30(1):34-43. doi: 10.1159/000200769
  42. Rampanelli E, Rouschop K, Teske GJ, et al. CD44v3-v10 reduces the profibrotic effects of TGF-beta1 and attenuates tubular injury in the early stage of chronic obstructive nephropathy. Am J Physiol Renal Physiol. 2013;305:F1445-54. doi: 10.1152/ajprenal.00340.2013
  43. Tan X, Li Y, Liu Y. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol. 2006;17(12):3382-93. doi: 10.1681/ASN.2006050520
  44. Panichi V, Migliori M, Taccola D, et al. Effects of 1,25(OH)2D3 in experimental mesangial proliferative nephritis in rats. Kidney Int. 2001;60(1):87-95. doi: 10.1046/j.1523-1755.2001.00775.x
  45. Li YC. Chapter 45 – Vitamin D and the Renin-Angiotensin System. In: Vitamin D, 4th ed, Feldman D, Ed., MA, USA, 2018; p. 825-47. doi: 10.1016/B978-0-12-809965-0.00045-8
  46. Hamzawy M, Gouda SAA, Rashed L, et al. 22-Oxacalcitriol prevents acute kidney injury via inhibition of apoptosis and enhancement of autophagy. Clin Exp Nephrol. 2019;23(1):43-55. doi: 10.1007/s10157-018-1614-y
  47. Suh SH, Lee KE, Park JW, et al. Antiapoptotic effect of paricalcitol in gentamicin-induced kidney injury. Korean J Physiol Pharmacol. 2013;17(5):435-40. doi: 10.4196/kjpp.2013.17.5.435
  48. Ali SB, Perdawood D, Abdulrahman R, et al. Vitamin D deficiency as a risk factor for urinary tract infection in women at reproductive age. Saudi J Biol Sci. 2020;27(11):2942-7. doi: 10.1016/j.sjbs.2020.08.008.
  49. Haghdoost S, Pazandeh F, Darvish S, et al. Association of serum vitamin D levels and urinary tract infection in pregnant women: A case control study. Eur J Obstet Gynecol Reprod Biol. 2019;243:51-6. doi: 10.1016/j.ejogrb.2019.10.015
  50. Цуцаева А.Н., Захарова И.Н., Климов Л.Я., и др. Обеспеченность витамином D у детей с инфекцией мочевыводящих путей. Педиатрия. Consilium Medicum; 2023:2:193-7 [Tsutsaeva AN, Zakharova IN, Klimov LYa, et al. Vitamin D supplementation in children with urinary tract infection. Pediatrics. Consilium Medicum. 2023;2:193-7 (in Russian)]. doi: 10.26442/26586630.2023.2.202321
  51. Deng QF, Chu H, Wen Z, Cao YS. Vitamin D and Urinary Tract Infection: A systematic review and meta-analysis. Ann Clin Lab Sci. 2019;49(1):134-42. Available at: http://www.annclinlabsci.org/content/49/1/134.long. Accessed: 15.01.2024
  52. Kwon YE, Kim H, Oh HJ, et al. Vitamin D deficiency is an independent risk factor for urinary tract infections after renal transplants. Medicine (Baltimore). 2015;94(9):e594. doi: 10.1097/MD.0000000000000594
  53. Hertting O, Lüthje P, Sullivan D, et al. Vitamin D-deficient mice have more invasive urinary tract infection. PLoS One. 2017;12(7):e0180810. doi: 10.1371/journal.pone.0180810
  54. Захарова И.Н., Цуцаева А.Н., Долбня С.В., и др. Инфекции мочевых путей и витамин D: перспективы использования в профилактие и лечении. Медицинский совет. 2021;11:148-55 [Zakharova IN, Tsutsaeva AN, Dolbnya SV, et al. Urinary tract infections and vitamin D: prospects for use in prevention and treatment. Meditsinskiy sovet. 2021;11:148-55 (in Russian)]. doi: 10.21518/2079-701X-2021-11-148-155
  55. Захарова И.Н., Османов И.М., Климов Л.Я., и др. Роль антимикробных пептидов в защите от инфекций мочевых путей. Медицинский совет. 2019;2:143-50 [Zakharova IN, Osmanov IM, Klimov LYa, et al. The role of antimicrobial peptides in defending the urinary tract against infections. Meditsinsky Sovet. 2019;2:143-50 (in Russian)]. doi: 10.21518/2079-701X-2019-2-143-150
  56. Цуцаева А.Н., Климов Л.Я., Минасян А.К., и др. Уровень антимикробных пептидов у детей с инфекцией мочевыводящих путей. Медицинский вестник Северного Кавказа. 2024;19(1):34-8 [Tsutsaeva AN, Klimov LYa, Minasyan AK, et al. Level of antimicrobial peptides in children with urinary tract infection. Medical News of North Caucasus. 2024;19(1):34-8 (in Russian)]. doi: 10.14300/mnnc.2024.19007
  57. Teng M, Wolf M, Ofsthun MN, et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005;16(4):1115-25. doi: 10.1681/ASN.2004070573
  58. Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70(4):771-80. doi: 10.1038/sj.ki.5001514
  59. Ravani P, Malberti F, Tripepi G, et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2009;75(1):88-95. doi: 10.1038/ki.2008.501
  60. Pilz S, Iodice S, Zittermann A, et al. Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis. 2011;58(3):374-82. doi: 10.1053/j.ajkd.2011.03.020
  61. Verma V, Lamture Y, Ankar R. Management of Uremic Xerosis and Chronic Kidney Disease (CKD)-Associated Pruritus (CKD-Ap) With Topical Preparations: A Systematic Review and Implications in the Indian Context. Cureus. 2023;15(7):e42587. doi: 10.7759/cureus.42587
  62. de Zeeuw D, Agarwal R, Amdahl M, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010;376(9752):1543-51. doi: 10.1016/S0140-6736(10)61032-X
  63. de Borst MH, Hajhosseiny R, Tamez H, et al. Active vitamin D treatment for reduction of residual proteinuria: a systematic review. J Am Soc Nephrol. 2013;24(11):1863-71. doi: 10.1681/ASN.2013030203
  64. Bai YJ, Li YM, Hu SM, et al. Vitamin D supplementation reduced blood Inflammatory cytokines expression and Improved graft function in kidney transplant recipients. Front Immunol. 2023;14:1152295. doi: 10.3389/fimmu.2023.1152295

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2. Fig. 1. Vitamin D metabolism in health [adapted from 4, 5].

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3. Fig. 2. Features of vitamin D metabolism in patients with impaired renal function (adapted from [11]).

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