Skip to main content

Advertisement

Springer Nature Link
Log in

The role of uric acid in mineral bone disorders in chronic kidney disease

  • Review
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Increasing survival in the chronic kidney disease (CKD) population exposes the bone to the cumulative detrimental sequelae of CKD, now defined physiologically and histopathologically as chronic kidney disease mineral bone disorder (CKD-BMD). This disorder is increasingly recognized as a “nontraditional” driver of morbidity and mortality and presents an opportunity to improve CKD outcomes via research. However, recent advances in the literature on this topic have not yet been collected into a single review. Therefore, this report aims to discuss the disordered renal-bone axis in CKD-BMD, molecular and hormonal drivers, novel treatment strategies, and forthcoming research in a clinician-directed format. A key novel topic will be the unique impact of uric acid on CKD-BMD, which is poised to apply extensive existing research in the uric acid domain to benefit the CKD-BMD population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Covic A, Kanbay M, Voroneanu L, Turgut F, Serban DN, Serban IL et al (2010) Vascular calcification in chronic kidney disease. Clin Sci (Lond). 119(3):111–121

    Article  CAS  PubMed  Google Scholar 

  2. Sag AA, Covic A, London G, Vervloet M, Goldsmith D, Gorriz JL et al (2016) Clinical imaging of vascular disease in chronic kidney disease. Int Urol Nephrol 48(6):827–837

    Article  PubMed  Google Scholar 

  3. Kanbay M, Goldsmith D, Akcay A, Covic A (2009) Phosphate—the silent stealthy cardiorenal culprit in all stages of chronic kidney disease: a systematic review. Blood Purif 27(2):220–230

    Article  CAS  PubMed  Google Scholar 

  4. Afsar B, Turkmen K, Covic A, Kanbay M (2014) An update on coronary artery disease and chronic kidney disease. Int J Nephrol 2014:767424

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kanbay M, Nicoleta M, Selcoki Y, Ikizek M, Aydin M, Eryonucu B et al (2010) Fibroblast growth factor 23 and fetuin A are independent predictors for the coronary artery disease extent in mild chronic kidney disease. Clin J Am Soc Nephrol 5(10):1780–1786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kanbay M, Vervloet M, Cozzolino M, Siriopol D, Covic A, Goldsmith D et al (2017) Novel Faces of Fibroblast Growth Factor 23 (FGF23): iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury. Calcif Tissue Int 100(3):217–228

    Article  CAS  PubMed  Google Scholar 

  7. Kanbay M, Solak Y, Siriopol D, Aslan G, Afsar B, Yazici D et al (2016) Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis. Int Urol Nephrol 48(12):2029–2042

    Article  CAS  PubMed  Google Scholar 

  8. Kanbay M, Siriopol D, Saglam M, Kurt YG, Gok M, Cetinkaya H et al (2014) Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab 99(10):E1854–E1861

    Article  CAS  PubMed  Google Scholar 

  9. Hruska KA, Sugatani T, Agapova O, Fang Y (2017) The chronic kidney disease—mineral bone disorder (CKD-MBD): advances in pathophysiology. Bone 100:80–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hahn K, Kanbay M, Lanaspa MA, Johnson RJ, Ejaz AA (2017) Serum uric acid and acute kidney injury: a mini review. J Adv Res. 8(5):529–536

    Article  CAS  PubMed  Google Scholar 

  11. Jensen T, Niwa K, Hisatome I, Kanbay M, Andres-Hernando A, Roncal-Jimenez CA et al (2018) Increased serum uric acid over five years is a risk factor for developing fatty liver. Sci Rep. 8(1):11735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kanbay M, Jensen T, Solak Y, Le M, Roncal-Jimenez C, Rivard C et al (2016) Uric acid in metabolic syndrome: from an innocent bystander to a central player. Eur J Intern Med. 29:3–8

    Article  CAS  PubMed  Google Scholar 

  13. Takir M, Kostek O, Ozkok A, Elcioglu OC, Bakan A, Erek A et al (2015) Lowering uric acid with allopurinol improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. J Investig Med 63(8):924–929

    Article  CAS  PubMed  Google Scholar 

  14. Kanbay M, Yilmaz MI, Sonmez A, Turgut F, Saglam M, Cakir E et al (2011) Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease. Am J Nephrol 33(4):298–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kanbay M, Siriopol D, Nistor I, Elcioglu OC, Telci O, Takir M et al (2014) Effects of allopurinol on endothelial dysfunction: a meta-analysis. Am J Nephrol 39(4):348–356

    Article  CAS  PubMed  Google Scholar 

  16. Kanbay M, Solak Y, Dogan E, Lanaspa MA, Covic A (2010) Uric acid in hypertension and renal disease: the chicken or the egg? Blood Purif 30(4):288–295

    Article  CAS  PubMed  Google Scholar 

  17. Toyama T, Furuichi K, Shimizu M, Hara A, Iwata Y, Sakai N et al (2015) Relationship between serum uric acid levels and chronic kidney disease in a japanese cohort with normal or mildly reduced kidney function. PLoS One 10(9):e0137449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kanbay M, Yilmaz MI, Sonmez A, Solak Y, Saglam M, Cakir E et al (2012) Serum uric acid independently predicts cardiovascular events in advanced nephropathy. Am J Nephrol 36(4):324–331

    Article  CAS  PubMed  Google Scholar 

  19. Kanbay M, Ikizek M, Solak Y, Selcoki Y, Uysal S, Armutcu F et al (2011) Uric acid and pentraxin-3 levels are independently associated with coronary artery disease risk in patients with stage 2 and 3 kidney disease. Am J Nephrol 33(4):325–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. von Lueder TG, Girerd N, Atar D, Agewall S, Lamiral Z, Kanbay M et al (2015) Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the high-risk myocardial infarction database initiative. Eur J Heart Fail 17(11):1144–1151

    Article  CAS  Google Scholar 

  21. Turak O, Ozcan F, Tok D, Isleyen A, Sokmen E, Tasoglu I et al (2013) Serum uric acid, inflammation, and nondipping circadian pattern in essential hypertension. J Clin Hypertens (Greenwich). 15(1):7–13

    Article  CAS  Google Scholar 

  22. Cagli K, Turak O, Canpolat U, Ozcan F, Tok D, Mendi MA et al (2015) Association of serum uric acid level with blood pressure variability in newly diagnosed essential hypertension. J Clin Hypertens (Greenwich). 17(12):929–935

    Article  CAS  PubMed Central  Google Scholar 

  23. Kuwabara M, Kanbay M, Hisatome I (2018) Uric acid and hypertension because of arterial stiffness. Hypertension 72(3):582–584

    Article  CAS  PubMed  Google Scholar 

  24. Lundquist AL, Nigwekar SU (2016) Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease. Curr Opin Nephrol Hypertens 25(2):120–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA et al (2007) 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 71(1):31–38

    Article  CAS  PubMed  Google Scholar 

  26. Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H et al (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79(12):1370–1378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Farrow EG, Davis SI, Summers LJ, White KE (2009) Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J Am Soc Nephrol 20(5):955–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Juppner H, Wolf M, Salusky IB (2010) FGF-23: more than a regulator of renal phosphate handling? J Bone Miner Res 25(10):2091–2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Vervloet MG, Sezer S, Massy ZA, Johansson L, Cozzolino M, Fouque D et al (2017) The role of phosphate in kidney disease. Nat Rev Nephrol. 13(1):27–38

    Article  CAS  PubMed  Google Scholar 

  30. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: improving Global Outcomes (KDIGO). Kidney Int 69(11):1945–1953

    Article  CAS  PubMed  Google Scholar 

  31. Goodman WG (2005) The evolution of assays for parathyroid hormone. Semin Dial 18(4):296–301

    Article  PubMed  Google Scholar 

  32. Ferreira A, Drueke TB (2000) Biological markers in the diagnosis of the different forms of renal osteodystrophy. Am J Med Sci 320(2):85–89

    Article  CAS  PubMed  Google Scholar 

  33. Reiss AB, Miyawaki N, Moon J, Kasselman LJ, Voloshyna I, D’Avino R Jr et al (2018) CKD, arterial calcification, atherosclerosis and bone health: inter-relationships and controversies. Atherosclerosis. 278:49–59

    Article  CAS  PubMed  Google Scholar 

  34. Kanbay M, Afsar B, Gusbeth-Tatomir P, Covic A (2010) Arterial stiffness in dialysis patients: where are we now? Int Urol Nephrol 42(3):741–752

    Article  PubMed  Google Scholar 

  35. Bikle DD (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21(3):319–329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Peng H, Li H, Li C, Chao X, Zhang Q, Zhang Y (2013) Association between vitamin D insufficiency and elevated serum uric acid among middle-aged and elderly Chinese Han women. PLoS One 8(4):e61159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yilmaz H, Kaya M, Sahin M, Delibasi T (2012) Is vitamin D status a predictor glycaemic regulation and cardiac complication in type 2 diabetes mellitus patients? Diabetes Metab Syndr. 6(1):28–31

    Article  PubMed  Google Scholar 

  38. Vanholder R, Patel S, Hsu CH (1993) Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure. J Am Soc Nephrol 4(4):1035–1038

    CAS  PubMed  Google Scholar 

  39. Takahashi S, Yamamoto T, Moriwaki Y, Tsutsumi Z, Yamakita J, Higashino K (1998) Decreased serum concentrations of 1,25(OH)2-vitamin D3 in patients with gout. Metabolism. 47(3):336–338

    Article  CAS  PubMed  Google Scholar 

  40. Hsu CH, Patel SR, Young EW, Vanholder R (1991) Effects of purine derivatives on calcitriol metabolism in rats. Am J Physiol 260(4 Pt 2):F596–F601

    CAS  PubMed  Google Scholar 

  41. Chen W, Roncal-Jimenez C, Lanaspa M, Gerard S, Chonchol M, Johnson RJ et al (2014) Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo. Metabolism. 63(1):150–160

    Article  CAS  PubMed  Google Scholar 

  42. Thakkinstian A, Anothaisintawee T, Chailurkit L, Ratanachaiwong W, Yamwong S, Sritara P et al (2015) Potential causal associations between vitamin D and uric acid: bidirectional mediation analysis. Sci Rep. 5:14528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Chin KY, Nirwana SI, Ngah WZ (2015) Significant association between parathyroid hormone and uric acid level in men. Clin Interv Aging 10:1377–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hui JY, Choi JW, Mount DB, Zhu Y, Zhang Y, Choi HK (2012) The independent association between parathyroid hormone levels and hyperuricemia: a national population study. Arthritis Res Ther. 14(2):R56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alemzadeh R, Kichler J (2016) Uric acid-induced inflammation is mediated by the parathyroid hormone: 25-hydroxyvitamin D ratio in obese adolescents. Metab Syndr Relat Disord. 14(3):167–174

    Article  CAS  PubMed  Google Scholar 

  46. Saleh F, Jorde R, Sundsfjord J, Haug E, Figenschau Y (2006) Causes of secondary hyperparathyroidism in a healthy population: the Tromso study. J Bone Miner Metab 24(1):58–64

    Article  PubMed  Google Scholar 

  47. Hisatome I, Ishimura M, Sasaki N, Yamakawa M, Kosaka H, Tanaka Y et al (1992) Renal handling of urate in two patients with hyperuricemia and primary hyperparathyroidism. Intern Med 31(6):807–811

    Article  CAS  PubMed  Google Scholar 

  48. Westerdahl J, Valdemarsson S, Lindblom P, Bergenfelz A (2001) Urate and arteriosclerosis in primary hyperparathyroidism. Clin Endocrinol (Oxf) 54(6):805–811

    Article  CAS  Google Scholar 

  49. Bergenfelz A, Bladstrom A, Their M, Nordenstrom E, Valdemarsson S, Westerdahl J (2007) Serum levels of uric acid and diabetes mellitus influence survival after surgery for primary hyperparathyroidism: a prospective cohort study. World J Surg. 31(7):1393–1400 (discussion 401-2)

    Article  PubMed  Google Scholar 

  50. Valdemarsson S, Lindblom P, Bergenfelz A (1998) Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 244(3):241–249

    Article  CAS  PubMed  Google Scholar 

  51. Christensson T (1977) Serum urate in subjects with hypercalcaemic hyperparathyroidism. Clin Chim Acta 80(3):529–533

    Article  CAS  PubMed  Google Scholar 

  52. Dalbeth N, Horne A, Gamble GD, Ames R, Mason B, McQueen FM et al (2009) The effect of calcium supplementation on serum urate: analysis of a randomized controlled trial. Rheumatology (Oxford) 48(2):195–197

    Article  CAS  Google Scholar 

  53. Miller PD, Schwartz EN, Chen P, Misurski DA, Krege JH (2007) Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 18(1):59–68

    Article  CAS  PubMed  Google Scholar 

  54. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y et al (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19(3):429–435

    Article  CAS  PubMed  Google Scholar 

  55. Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson KB (2003) 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 64(6):2272–2279

    Article  CAS  PubMed  Google Scholar 

  56. Mirza MA, Larsson A, Lind L, Larsson TE (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis. 205(2):385–390

    Article  CAS  PubMed  Google Scholar 

  57. Sakoh T, Nakayama M, Tsuchihashi T, Yoshitomi R, Tanaka S, Katafuchi E et al (2016) Associations of fibroblast growth factor 23 with urate metabolism in patients with chronic kidney disease. Metabolism. 65(10):1498–1507

    Article  CAS  PubMed  Google Scholar 

  58. Asicioglu E, Kahveci A, Arikan H, Koc M, Tuglular S, Ozener C (2014) Fibroblast growth factor-23 levels are associated with uric acid but not carotid intima media thickness in renal transplant recipients. Transplant Proc. 46(1):180–183

    Article  CAS  PubMed  Google Scholar 

  59. Gutierrez OM, Wolf M, Taylor EN (2011) Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin J Am Soc Nephrol 6(12):2871–2878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wolf M (2010) Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 21(9):1427–1435

    Article  CAS  PubMed  Google Scholar 

  61. Andres M, Quintanilla MA, Sivera F, Sanchez-Paya J, Pascual E, Vela P et al (2016) Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: an exploratory study. Arthritis Rheumatol. 68(6):1531–1539

    Article  CAS  PubMed  Google Scholar 

  62. Kim H, Kim SH, Choi AR, Kim S, Choi HY, Kim HJ et al (2017) Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease: a single-center cross-sectional study. Medicine (Baltimore). 96(14):e6565

    Article  PubMed  PubMed Central  Google Scholar 

  63. Mehta T, Nuccio E, McFann K, Madero M, Sarnak MJ, Jalal D (2015) Association of uric acid with vascular stiffness in the framingham heart study. Am J Hypertens 28(7):877–883

    Article  CAS  PubMed  Google Scholar 

  64. Lee CT, Chua S, Hsu CY, Tsai YC, Ng HY, Kuo CC et al (2013) Biomarkers associated with vascular and valvular calcification in chronic hemodialysis patients. Dis Markers 34(4):229–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Andrews ES, Perrenoud L, Nowak KL, You Z, Pasch A, Chonchol M et al (2018) Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post hoc analysis of a randomized clinical trial. PLoS One 13(10):e0205831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kanbay M, Ozkara A, Selcoki Y, Isik B, Turgut F, Bavbek N et al (2007) Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol 39(4):1227–1233

    Article  CAS  PubMed  Google Scholar 

  67. Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincon A et al (2010) Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 5(8):1388–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kanbay M, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I et al (2011) A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol 6(8):1887–1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nabipour I, Sambrook PN, Blyth FM, Janu MR, Waite LM, Naganathan V et al (2011) Serum uric acid is associated with bone health in older men: a cross-sectional population-based study. J Bone Miner Res 26(5):955–964

    Article  CAS  PubMed  Google Scholar 

  70. Ahn SH, Lee SH, Kim BJ, Lim KH, Bae SJ, Kim EH et al (2013) Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women. Osteoporos Int 24(12):2961–2970

    Article  CAS  PubMed  Google Scholar 

  71. Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y (2009) Oxidative stress in bone remodelling and disease. Trends Mol Med. 15(10):468–477

    Article  CAS  PubMed  Google Scholar 

  72. Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS et al (2005) A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106(3):852–859

    Article  CAS  PubMed  Google Scholar 

  73. Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P et al (2003) Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab 88(4):1523–1527

    Article  CAS  PubMed  Google Scholar 

  74. Makovey J, Macara M, Chen JS, Hayward CS, March L, Seibel MJ et al (2013) Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: a longitudinal study. Bone 52(1):400–406

    Article  CAS  PubMed  Google Scholar 

  75. Kim BJ, Baek S, Ahn SH, Kim SH, Jo MW, Bae SJ et al (2014) Higher serum uric acid as a protective factor against incident osteoporotic fractures in Korean men: a longitudinal study using the National Claim Registry. Osteoporos Int 25(7):1837–1844

    Article  CAS  PubMed  Google Scholar 

  76. Zhao DD, Jiao PL, Yu JJ, Wang XJ, Zhao L, Xuan Y et al (2016) Higher serum uric acid is associated with higher bone mineral density in Chinese men with type 2 diabetes mellitus. Int J Endocrinol. 2016:2528956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Chen Z, Ding Z, Fu C, Yu C, Ma G (2014) Correlation between serum uric Acid and renal function in patients with stable coronary artery disease and type 2 diabetes. J Clin Med Res. 6(6):443–450

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Kamei K, Konta T, Hirayama A, Suzuki K, Ichikawa K, Fujimoto S et al (2014) A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population. Nephrol Dial Transplant 29(12):2286–2292

    Article  CAS  PubMed  Google Scholar 

  79. Malmgren L, McGuigan F, Christensson A, Akesson KE (2017) Reduced kidney function is associated with BMD, bone loss and markers of mineral homeostasis in older women: a 10-year longitudinal study. Osteoporos Int 28(12):3463–3473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhang D, Bobulescu IA, Maalouf NM, Adams-Huet B, Poindexter J, Park S et al (2015) Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia. J Bone Miner Res 30(6):992–999

    Article  CAS  PubMed  Google Scholar 

  81. Nybo M, Jespersen B, Aarup M, Ejersted C, Hermann AP, Brixen K (2013) Determinants of bone mineral density in patients on haemodialysis or peritoneal dialysis—a cross-sectional, longitudinal study. Biochem Med (Zagreb). 23(3):342–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Denburg MR, Tsampalieros AK, de Boer IH, Shults J, Kalkwarf HJ, Zemel BS et al (2013) Mineral metabolism and cortical volumetric bone mineral density in childhood chronic kidney disease. J Clin Endocrinol Metab 98(5):1930–1938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Park SH, Jia T, Qureshi AR, Barany P, Heimburger O, Larsson TE et al (2013) Determinants and survival implications of low bone mineral density in end-stage renal disease patients. J Nephrol. 26(3):485–494

    Article  CAS  PubMed  Google Scholar 

  84. Perez-Gomez MV, Bartsch LA, Castillo-Rodriguez E, Fernandez-Prado R, Kanbay M, Ortiz A. Potential dangers of serum urate-lowering therapy. Am J Med. 2019

  85. Barreto FC, Costa C, Reis LMD, Custodio MR. Bone biopsy in nephrology practice. J Bras Nefrol. 2018

  86. Cheng Q, Wu X, Du Y, Hong W, Tang W, Li H et al (2018) Levels of serum sclerostin, FGF-23, and intact parathyroid hormone in postmenopausal women treated with calcitriol. Clin Interv Aging 13:2367–2374

    Article  PubMed  PubMed Central  Google Scholar 

  87. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  CAS  PubMed  Google Scholar 

  88. Grieco GE, Cataldo D, Ceccarelli E, Nigi L, Catalano G, Brusco N et al (2018) Serum levels of miR-148a and miR-21-5p are increased in Type 1 diabetic patients and correlated with markers of bone strength and metabolism. Noncoding RNA. 4(4):37

    CAS  PubMed Central  Google Scholar 

  89. Yao CJ, Lv Y, Zhang CJ, Jin JX, Xu LH, Jiang J et al (2018) MicroRNA-185 inhibits the growth and proliferation of osteoblasts in fracture healing by targeting PTH gene through down-regulating Wnt/beta-catenin axis: in an animal experiment. Biochem Biophys Res Commun 501(1):55–63

    Article  CAS  PubMed  Google Scholar 

  90. Shilo V, Mor-Yosef Levi I, Abel R, Mihailovic A, Wasserman G, Naveh-Many T et al (2017) Let-7 and MicroRNA-148 regulate parathyroid hormone levels in secondary hyperparathyroidism. J Am Soc Nephrol 28(8):2353–2363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Jeong S, Oh JM, Oh KH, Kim IW (2017) Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients. PLoS One 12(2):e0170535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Shao Y, Ren H, Lv C, Ma X, Wu C, Wang Q (2017) Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease. Endocrine 55(1):130–138

    Article  CAS  PubMed  Google Scholar 

  93. Tang ZM, Fang M, Wang JP, Cai PC, Wang P, Hu LH (2014) Clinical relevance of plasma miR-21 in new-onset systemic lupus erythematosus patients. J Clin Lab Anal 28(6):446–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Hong Q, Yu S, Geng X, Duan L, Zheng W, Fan M et al (2015) High concentrations of uric acid inhibit endothelial cell migration via miR-663 which regulates phosphatase and tensin homolog by targeting transforming growth factor-beta1. Microcirculation. 22(4):306–314

    Article  CAS  PubMed  Google Scholar 

  95. Yu S, Hong Q, Wang Y, Hou K, Wang L, Zhang Y et al (2015) High concentrations of uric acid inhibit angiogenesis via regulation of the Kruppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a. Circ J 79(11):2487–2498

    Article  CAS  PubMed  Google Scholar 

  96. Evenepoel P, D’Haese P, Brandenburg V (2015) Sclerostin and DKK1: new players in renal bone and vascular disease. Kidney Int 88(2):235–240

    Article  CAS  PubMed  Google Scholar 

  97. Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register TC et al (2014) CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol 25(8):1760–1773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sugatani T, Agapova OA, Fang Y, Berman AG, Wallace JM, Malluche HH et al (2017) Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease. Kidney Int 91(1):86–95

    Article  CAS  PubMed  Google Scholar 

  99. Sugatani T (2018) Systemic activation of activin a signaling causes chronic kidney disease-mineral bone disorder. Int J Mol Sci. 19(9):2490

    Article  CAS  PubMed Central  Google Scholar 

  100. Peng LN, Chou MY, Liang CK, Lee WJ, Kojima T, Lin MH et al (2018) Association between serum activin A and metabolic syndrome in older adults: potential of activin A as a biomarker of cardiometabolic disease. Exp Gerontol 111:197–202

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

MK The authors gratefully acknowledge use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.

Funding

This study was not funded by any grant.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey

    Baris Afsar

  2. Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, USA

    Alan A. Sag

  3. Department of Medicine, School of Medicine, Koç University, Istanbul, Turkey

    Cinar Oztosun

  4. Department of Cardiology, Toranomon Hospital, Tokyo, Japan

    Masanari Kuwabara

  5. Renal Division, Department of Health Sciences, University of Milan, 20142, Milan, Italy

    Mario Cozzolino

  6. Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, Iasi, Romania

    Adrian Covic

  7. Division of Nephrology, Department of Medicine, Koc University School of Medicine, Rumelifeneri Yolu, Sariyer, 34450, Istanbul, Turkey

    Mehmet Kanbay

Authors
  1. Baris Afsar
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Alan A. Sag
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Cinar Oztosun
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Masanari Kuwabara
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Mario Cozzolino
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Adrian Covic
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Mehmet Kanbay
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Mehmet Kanbay.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afsar, B., Sag, A.A., Oztosun, C. et al. The role of uric acid in mineral bone disorders in chronic kidney disease. J Nephrol 32, 709–717 (2019). https://doi.org/10.1007/s40620-019-00615-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-019-00615-0

Keywords