Abstract
Background
Recent studies suggest that cytokines modulate bone turnover. Idiopathic hypercalciuria (IH) seems to be associated with bone mineral loss. Therefore, the aim of this study was to assess cytokines involved in bone turnover in patients with IH.
Methods
Plasma and spot-urine levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein (MCP-1) were measured in 70 children and adolescents with IH and in 37 healthy controls. Patients with IH were subdivided according to their calciuria at the time of sample collection: ≥4 mg/kg/day (persistent IH, n=27) and below 4 mg/kg/day (controlled IH, n=43). Cytokines were determined by enzyme-linked immunoassay.
Results
Plasma and urinary concentrations of IL-1β, IL-6, IL-8, and TNF-α were undetectable in all groups. No differences were found between controlled and persistent hypercalciuria for plasma and urinary levels of MCP-1 and TGF-β1. On the other hand, MCP-1 levels were significantly higher in both subgroups of IH in comparison to healthy controls. Furthermore, urinary MCP-1 levels of IH patients correlated positively with bone mineral content (p=0.013).
Conclusion
Although cytokine measurements did not allow the differentiation between persistent and controlled IH, our findings suggest that MCP-1 might play a role in patients with IH.
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References
Albright F, Henneman P, Benedict PH, Forbes AP (1953) Idiopathic hypercalciuria: a preliminary report. Proc R Soc Med 46:1077–1081
Ammenti A, Neri E, Agistri R, Beseghi U, Bacchini E (2006) Idiopathic hypercalciuria in infants with renal stones. Pediatr Nephrol 21:1901–1903
Moore ES, Coe FL, McMann BJ, Favus MJ (1978) Idiopathic hypercalciuria in children: prevalence and metabolic characteristics. J Pediatr 92:906–910
Spivacow FR, Negri AL, del Valle EE, Calvino I, Zanchetta JR (2010) Clinical and metabolic risk factor evaluation in young adults with kidney stones. Int Urol Nephrol 42:471–475
Frick KK, Bushinsky DA (2003) Molecular mechanisms of primary hypercalciuria. J Am Soc Nephrol 14:1082–1095
Zerwekh JE (2010) Bone disease and hypercalciuria in children. Pediatr Nephrol 25:395–401
Zerwekh JE (2008) Bone disease and idiopathic hypercalciuria. Semin Nephrol 28:133–142
Weisinger JR, Alonzo E, Carlini RG, Paz-Martinez V, Martinis R, Bellorin-Font E (1998) Bone disease in hypercalciuria: a new form of osteodystrophy? Nephrol Dial Transplant 13 [Suppl 3]:88–90
Weisinger JR (1996) New insights into the pathogenesis of idiopathic hypercalciuria: the role of bone. Kidney Int 49:1507–1518
Tasca A, Dalle Carbonare L, Nigro F, Giannini S (2009) Bone disease in patients with primary hypercalciuria and calcium nephrolithiasis. Urology 74:22–27
Skalova S, Palicka V, Kutilek S (2005) Bone mineral density and urinary N-acetyl-beta-D-glucosaminidase activity in paediatric patients with idiopathic hypercalciuria. Nephrology (Carlton) 10:99–102
Schwaderer AL, Cronin R, Mahan JD, Bates CM (2008) Low bone density in children with hypercalciuria and/or nephrolithiasis. Pediatr Nephrol 23:2209–2214
Polito C, Iolascon G, Nappi B, Andreoli S, La Manna A (2003) Growth and bone mineral density in long-lasting idiopathic hypercalciuria. Pediatr Nephrol 18:545–547
Giannini S, Nobile M, Sella S, Dalle Carbonare L (2005) Bone disease in primary hypercalciuria. Crit Rev Clin Lab Sci 42:229–248
Garcia-Nieto V, Ferrandez C, Monge M, de Sequera M, Rodrigo MD (1997) Bone mineral density in pediatric patients with idiopathic hypercalciuria. Pediatr Nephrol 11:578–583
Garcia-Nieto V, Navarro JF, Ferrandez C (1998) Bone loss in children with idiopathic hypercalciuria. Nephron 78:341–342
Penido MG, Lima EM, Souto MF, Marino VS, Tupinamba AL, Franca A (2006) Hypocitraturia: a risk factor for reduced bone mineral density in idiopathic hypercalciuria? Pediatr Nephrol 21:74–78
Penido MG, Lima EM, Marino VS, Tupinamba AL, Franca A, Souto MF (2003) Bone alterations in children with idiopathic hypercalciuria at the time of diagnosis. Pediatr Nephrol 18:133–139
Pfeilschifter J, Chenu C, Bird A, Mundy GR, Roodman GD (1989) Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res 4:113–118
Weisinger JR, Alonzo E, Bellorin-Font E, Blasini AM, Rodriguez MA, Paz-Martinez V, Martinis R (1996) Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. Kidney Int 49:244–250
Gowen M, Mundy GR (1986) Actions of recombinant interleukin 1, interleukin 2, and interferon-gamma on bone resorption in vitro. J Immunol 136:2478–2482
Gomes SA, dos Reis LM, Noronha IL, Jorgetti V, Heilberg IP (2008) RANKL is a mediator of bone resorption in idiopathic hypercalciuria. Clin J Am Soc Nephrol 3:1446–1452
Freundlich M, Alonzo E, Bellorin-Font E, Weisinger JR (2002) Reduced bone mass in children with idiopathic hypercalciuria and in their asymptomatic mothers. Nephrol Dial Transplant 17:1396–1401
Misael da Silva AM, dos Reis LM, Pereira RC, Futata E, Branco-Martins CT, Noronha IL, Wajchemberg BL, Jorgetti V (2002) Bone involvement in idiopathic hypercalciuria. Clin Nephrol 57:183–191
Santos ACS Jr, Lima EM, Oliveira EA, Simões e Silva AC (2011) Bone disease and cytokines in idiopathic hypercalciuria: a review. J Pediatr Endocrinol Metab 24:405–410
Butani L, Kalia A (2004) Idiopathic hypercalciuria in children—how valid are the existing diagnostic criteria? Pediatr Nephrol 19:577–582
Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115:2598–2608
Hughes P (2007) The CARI guidelines. Kidney stones: metabolic evaluation. Nephrology (Carlton) 12 [Suppl 1]:31–33
Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S (2008) International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions. Bone 43:1115–1121
Brandao CM, Camargos BM, Zerbini CA, Plapler PG, Mendonca LM, Albergaria BH, Pinheiro MM, Prado M, Eis SR (2009) 2008 official positions of the Brazilian Society for Clinical Densitometry—SBDens. Arq Bras Endocrinol Metabol 53:107–112
Baroncelli GI, Bertelloni S, Sodini F, Saggese G (2005) Osteoporosis in children and adolescents: etiology and management. Paediatr Drugs 7:295–323
Souto MF, Teixeira AL, Russo RC, Penido MG, Silveira KD, Teixeira MM, Simoes e Silva AC (2008) Immune mediators in idiopathic nephrotic syndrome: evidence for a relation between interleukin 8 and proteinuria. Pediatr Res 64:637–642
Volejnikova S, Laskari M, Marks SC Jr, Graves DT (1997) Monocyte recruitment and expression of monocyte chemoattractant protein-1 are developmentally regulated in remodeling bone in the mouse. Am J Pathol 150:1711–1721
Yadav A, Saini V, Arora S (2010) MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta 411:1570–1579
Posner LJ, Miligkos T, Gilles JA, Carnes DL, Taddeo DR, Graves DT (1997) Monocyte chemoattractant protein-1 induces monocyte recruitment that is associated with an increase in numbers of osteoblasts. Bone 21:321–327
Lorenzo J, Horowitz M, Choi Y (2008) Osteoimmunology: interactions of the bone and immune system. Endocr Rev 29:403–440
Quinn JM, Itoh K, Udagawa N, Hausler K, Yasuda H, Shima N, Mizuno A, Higashio K, Takahashi N, Suda T, Martin TJ, Gillespie MT (2001) Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res 16:1787–1794
Pacifici R (2010) The immune system and bone. Arch Biochem Biophys 503:41–53
Pacifici R, Rothstein M, Rifas L, Lau KH, Baylink DJ, Avioli LV, Hruska K (1990) Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria. J Clin Endocrinol Metab 71:138–145
Giannini S, Nobile M, Sartori L, Dalle Carbonare L, Ciuffreda M, Corrò P, D’Angelo A, Calò L, Crepaldi G (1999) Acute effects of moderate dietary protein restriction in patients with idiopathic hypercalciuria and calcium nephrolithiasis. Am J Clin Nutr 69:267–271
Shroff R, Knott C, Rees L (2010) The virtues of vitamin D—but how much is too much? Pediatr Nephrol 25:1607–1620
Soylemezoglu O, Ozkaya O, Gonen S, Misirlioglu M, Kalman S, Buyan N (2004) Vitamin D receptor gene polymorphism in hypercalciuric children. Pediatr Nephrol 19:724–727
Borges JL, Brandao CM (2006) Low bone mass in children and adolescents. Arq Bras Endocrinol Metabol 50:775–782
Ghazali A, Fuentes V, Desaint C, Bataille P, Westeel A, Brazier M, Prin L, Fournier A (1997) Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria. J Clin Endocrinol Metab 82:32–38
Acknowledgements
This study was partially supported by CNPq (Brazilian National Research Council) and FAPEMIG (Foundation of Research Support of Minas Gerais). Dr. A.C. Simões e Silva, Dr. E.A. Oliveira, Dr E.M. Lima, and Dr. M.M. Teixeira had a scientific productivity grant from the CNPq. Dr. A.C. Simões e Silva and Dr. E.A. Oliveira also received the Grant INCT-MM (FAPEMIG: CBB-APQ-00075-09 / CNPq 573646/2008-2).
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Santos, A.C.S., Lima, E.M., Penido, M.G.M.G. et al. Plasma and urinary levels of cytokines in patients with idiopathic hypercalciuria. Pediatr Nephrol 27, 941–948 (2012). https://doi.org/10.1007/s00467-011-2094-4
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DOI: https://doi.org/10.1007/s00467-011-2094-4