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Pediatric urolithiasis: causative factors, diagnosis and medical management

Abstract

Childhood urolithiasis is associated with considerable morbidity and recurrence. Many risk factors—including those metabolic, genetic, anatomic, dietary and environmental in nature—have been identified in children with urinary tract calculi. As pediatric urolithiasis with a metabolic etiology is the most common disease, evaluating the metabolic risk factors in patients is necessary to both effectively treat current stones and prevent recurrence. We discuss causative risk factors of pediatric urolithiasis, as well as the diagnostic and therapeutic approaches.

Key Points

  • Pediatric urolithiasis is a common health problem worldwide with many causes, including environmental, dietary and genetic; the most common disease has a metabolic etiology

  • Metabolic risk factors include hypercalciuria, hyperuricosuria, hyperoxaluria and cystinuria

  • Diagnostic evaluation should aim to rule out anatomic obstruction, determine the history of the patient (including familial risk factors) and involve urine analysis

  • Therapy should be targeted at the risk factors causing urolithiasis, although therapy should include increasing daily fluid intake

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Figure 1: Diagnostic approach for pediatric urolithiasis.

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References

  1. Clayton, D. B. & Pope J. C. The increasing pediatric stone disease problem. Ther. Adv. Urol. 3, 3–12 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Edvardsson, V., Elidottir, H., Indridason, O. S. & Palsson, R. High incidence of kidney stones in Icelandic children. Pediatr. Nephrol. 20, 940–944 (2005).

    Article  PubMed  Google Scholar 

  3. Sas, D. J., Hulsey, T. C., Shatat, I. F. & Orak, J. K. Increasing incidence of kidney stones in children evaluated in the emergency department. J. Pediatr. 157, 132–137 (2010).

    Article  PubMed  Google Scholar 

  4. Bush, N. C. Re: epidemiological trends in pediatric urolithiasis. Editorial comment. J. Urol. 18, 1104–1105 (2010).

    Article  Google Scholar 

  5. Routh, J. C., Graham, D. A. & Nelson, C. P. Epidemiological trends in pediatric urolithiasis at United States freestanding pediatric hospitals. J. Urol. 184, 1100–1104 (2010).

    Article  PubMed  Google Scholar 

  6. Milliner, D. S. & Murphy, M. E. Urolithiasis in pediatric patients. Mayo Clin. Proc. 68, 241–248 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Karabacak, O. R., Ipek, B., Ozturk, U., Demirel, F., Saltas, H. & Altug, U. Metabolic evaluation in stone disease metabolic differences between the pediatric and adult patients with stone disease. Urology 76, 238–241 (2010).

    Article  PubMed  Google Scholar 

  8. Spivacow, F. R., Negri A. L., del Valle, E. E., Calviño, I. & Zanchetta, J. R. Clinical and metabolic risk factor evaluation in young adults with kidney stones. Int. Urol. Nephrol. 42, 471–475 (2010).

    Article  PubMed  Google Scholar 

  9. Acar, B., Inci Arikan, F., Emeksiz, S. & Dallar, Y. Risk factors for nephrolithiasis in children. World J. Urol. 26, 627–630 (2008).

    Article  PubMed  Google Scholar 

  10. Dursun, I. et al. Pediatric urolithiasis: an 8-year experience of single centre. Int. Urol. Nephrol. 40, 3–9 (2008).

    Article  PubMed  Google Scholar 

  11. Naseri, M., Varasteh, A. R. & Alamdaran, S. A. Metabolic factors associated with urinary calculi in children. Iran. J. Kidney Dis. 4, 32–38 (2010).

    PubMed  Google Scholar 

  12. Gürgöze, M. K. & Sarı, M. Y. Results of medical treatment and metabolic risk factors in children with urolithiasis. Pediatr. Nephrol. 26, 933–937 (2011).

    Article  PubMed  Google Scholar 

  13. Ertan, P., Tekin, G., Öger, N., Alkan, S. & Horasan, G. D. Metabolic and demographic characteristics of children with urolithiasis in western Turkey. Urol. Res. 39, 105–110 (2011).

    Article  PubMed  Google Scholar 

  14. Spivacow, F. R. et al. Metabolic risk factors in children with kidney stone disease. Pediatr. Nephrol. 23, 1129–1133 (2008).

    Article  PubMed  Google Scholar 

  15. Sarkissian, A. et al. Pediatric urolithiasis in Armenia: a study of 198 patients observed from 1991 to 1999. Pediatr. Nephrol. 16, 728–732 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Stapleton, F. B. Clinical approach to children with urolithiasis. Semin. Nephrol. 16, 389–397 (1996).

    CAS  PubMed  Google Scholar 

  17. Alpay, H., Ozen, A., Gokce, I. & Biyikli, N. Clinical and metabolic features of urolithiasis and microlithiasis in children. Pediatr. Nephrol. 24, 2203–2209 (2009).

    Article  PubMed  Google Scholar 

  18. Sarica, K. Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment. Urol. Res. 34, 96–101 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Diamond, D. A. Clinical patterns of pediatric urolithiasis. Br. J. Urol. 68, 195–198 (1991).

    Article  CAS  PubMed  Google Scholar 

  20. Polinsky, M. S., Kaiser, B. A. & Baluarte, H. J. Urolithiasis in childhood. Pediatr. Clin. North Am. 34, 683–710 (1987).

    Article  CAS  PubMed  Google Scholar 

  21. Basaklar, A. C. & Kale, N. Experience with childhood urolithiasis. Report of 196 cases. Br. J. Urol. 67, 203–205 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. van't Hoff, W. G. Aetiological factors in pediatric urolithiasis. Nephron Clin. Pract. 98, 45–48 (2004).

    Article  Google Scholar 

  23. Cameron, M. A., Sakhaee, K. & Moe, O. W. Nephrolithiasis in children. Pediatr. Nephrol. 20, 1587–1592 (2005).

    Article  PubMed  Google Scholar 

  24. Areses Trapote, R., Urbieta Garagorri, M. A., Ubetagoyena Arrieta, M., Mingo Monge, T. & Arruebarrena Lizarraga, D. Evaluation of renal stone disease: metabolic study. An. Pediatr. (Barc). 61, 418–427 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Nicoletta, J. A. & Lande, M. B. Medical evaluation and treatment of urolithiasis. Pediatr. Clin. North Am. 53, 479–491 (2006).

    Article  PubMed  Google Scholar 

  26. Choi, H., Synder, H. M. 3rd & Duckett, J. W. Urolithiasis in childhood: current management. J. Pediatr. Surg. 22, 158–164 (1987).

    Article  CAS  PubMed  Google Scholar 

  27. Miller, L. A. & Stapleton, F. B. Urinary volume in children with urolithiasis. J. Urol. 141, 918–920 (1989).

    Article  CAS  PubMed  Google Scholar 

  28. Lande, M. B., Varade, W., Erkan, E., Niederbracht, Y. & Schwartz, G. J. Role of urinary supersaturation in the evaluation of children with urolithiasis. Pediatr. Nephrol. 20, 491–494 (2005).

    Article  PubMed  Google Scholar 

  29. Milliner, D. in Pediatric Nephrology, 6th edn Ch. 58 (eds Avner, E. D., Harmon, W. E., Niaudet, P. & Yoshikawa, N.) 1405–1431 (Springer, Berlin, 2009).

    Book  Google Scholar 

  30. Hoppe, B., Milliner, D. & Leumann, E. in Comprehensive Pediatric Nephrology, 1st edn Ch. 33 (eds Geary, D. & Schaefer, F.) 499–525 (Mosby, Philadelphia, 2008).

    Book  Google Scholar 

  31. Schwaderer, A. L., Cronin, R., Mahan, J. D. & Bates, C. M. Low bone density in children with hypercalciuria and/or nephrolithiasis. Pediatr. Nephrol. 23, 2209–2214 (2008).

    Article  PubMed  Google Scholar 

  32. Sönmez, F., Akçanal, B., Altincik, A. & Yenisey, C. Urinary calcium excretion in healthy Turkish children. Int. Urol. Nephrol. 39, 917–922 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Sorkhi, H. & Haji Aahmadi, M. Urinary calcium to creatinin ratio in children. Indian J. Pediatr. 72, 1055–1056 (2005).

    Article  PubMed  Google Scholar 

  34. Butani, L. & Kalia, A. Idiopathic hypercalciuria in children—how valid are the existing diagnostic criteria? Pediatr. Nephrol. 19, 577–582 (2004).

    Article  PubMed  Google Scholar 

  35. Ammenti, A., Neri, E., Agistri, R., Beseghi, U. & Bacchini, E. Idiopathic hypercalciuria in infants with renal stones. Pediatr. Nephrol. 21, 1901–1903 (2006).

    Article  PubMed  Google Scholar 

  36. Coward, R. J. et al. Epidemiology of paediatric renal stone disease in the UK. Arch. Dis. Child. 88, 962–965 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hulton, S. A. Evaluation of urinary tract calculi in children. Arch. Dis. Child. 84, 320–323 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Aladjem, M., Barr, J., Lahat, E. & Bistritzer, T. Renal and absorptive hypercalciuria: a metabolic disturbance with varying and interchanging modes of expression. Pediatrics 97, 216–219 (1996).

    CAS  PubMed  Google Scholar 

  39. Coe, F. L., Parks, J. H. & Moore, E. S. Familial idiopathic hypercalciuria. N. Engl. J. Med. 300, 337–340 (1979).

    Article  CAS  PubMed  Google Scholar 

  40. Reed, B. Y., Heller, H. J., Gitomer, W. L. & Pak, C. Y. Mapping a gene defect in absorptive hypercalciuria to chromosome 1q23.3–q24. J. Clin. Endocrinol. Metab. 84, 3907–3913 (1999).

    CAS  PubMed  Google Scholar 

  41. Alon, U. S., Zimmerman, H. & Alon, M. Evaluation and treatment of pediatric idiophatic urolithiasis—revisited. Pediatr. Nephrol. 19, 516–520 (2004).

    Article  PubMed  Google Scholar 

  42. Karet, F. E. Inherited distal renal tubular acidosis. J. Am. Soc. Nephrol. 13, 2178–2184 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Jha, R. et al. Clinical profile of distal renal tubular acidosis. Saudi J. Kidney Dis. Transpl. 22, 261–267 (2011).

    PubMed  Google Scholar 

  44. Matlaga, B. R., Shah, O. D. & Assimos, D. G. Drug induced urinary calculi. Rev. Urol. 5, 227–231 (2003).

    PubMed  PubMed Central  Google Scholar 

  45. Cohen-Solal, F. et al. Urinary lithiasis in medical origine. Therapie 56, 743–750 (2001).

    CAS  PubMed  Google Scholar 

  46. Cochat, P., Fargue, S. & Harambat, J. in Pediatric Nephrology, 6th edn Ch. 58 (eds Avner, E. D., Harmon, W. E., Niaudet, P. & Yoshikawa, N.) 1069–1079 (Springer, Berlin, 2009).

    Book  Google Scholar 

  47. Hoppe, B., Beck, B. B. & Milliner, D. S. The primary hyperoxalurias. Kidney Int. 75, 1264–1271 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Belostotsky, R. et al. Mutations in DHDPSL are responsible for primary hyperoxaluria type III. Am. J. Hum. Genet. 87, 392–399 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Poyrazog˘lu, H. M. et al. Urinary uric acid: creatinine ratios in healthy Turkish children. Pediatr. Int. 51, 526–529 (2009).

    Article  CAS  Google Scholar 

  50. La Manna, A., Polito, C., Marte, A., Iovene, A. & Di Toro, R. Hyperuricosuria in children: clinical presentation and natural history. Pediatrics 107, 86–90 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Polito, C., La Manna, A., Nappi, B., Villani, J. & Di Toro, R. Idiopathic hypercalciuria and hyperuricosuria: family prevalence of nephrolithiasis. Pediatr. Nephrol. 14, 1102–1104 (2009).

    Google Scholar 

  52. Abate, N., Chandalia, M., Cabo-Chan, A. V., Moe, O. W. & Sakhaee, K. The metabolic syndrome and uric acid nephrolithiasis; novel features of renal manifestation of insulin resistance. Kidney Int. 65, 386–392 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Goodyer, P., Saadi, I., Ong, P., Elkas, G. & Rozen, R. Cystinuria subtype and risk of nephrolithiasis. Kidney Int. 54, 56–61 (1998).

    Article  CAS  PubMed  Google Scholar 

  54. Cochat, P. et al. Nephrolithiasis related to inborn metabolic disease. Pediatr. Nephrol. 25, 415–424 (2010).

    Article  PubMed  Google Scholar 

  55. Gargah, T., Essid, A., Labassi, A., Hamzaoui, M. & Lakhoua, M. R. Xanthine urolithiasis. Saudi J. Kidney Dis. Transpl. 21, 328–331 (2010).

    PubMed  Google Scholar 

  56. van den Berghe, G., Vincent, M. F. & Marie, S. in Inborn metabolic diseases: diagnosis and treatment. 5th edn (eds Fernandes, J., Saudubray, J. M., van den Berghe, G. & Walter, J. H.) 433–449 (Springer, Heidelberg, 2006).

    Book  Google Scholar 

  57. Sutor, D. J., Wooley, S. E. & Krízek, V. The composition of calculi from patients with alcaptonuria. Br. J. Urol. 42, 386–388 (1970).

    Article  CAS  PubMed  Google Scholar 

  58. Habbig, S., Beck, B. B. & Hoppe, B. Nephrocalcinosis and urolithiasis in children. Kidney Int. 80, 1278–1297 (2011).

    Article  PubMed  Google Scholar 

  59. Tekin, A. et al. A study of the etiology of idiopathic calcium urolithiasis in children: hypocitruria is the most important risk factor. J. Urol. 164, 162–165 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Akcay, T., Konukoglu, D. & Dincer, Y. Urinary glycosaminoglycan excretion in urolithiasis. Arch. Dis. Child. 80, 271–272 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Khan, S. R. & Kok, D. J. Modulators of urinary stone formation. Front. Biosci. 9, 1450–1482 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Gleeson, M. J. & Griffith, D. P. Struvite calculi. Br. J. Urol. 71, 503–511 (1993).

    Article  CAS  PubMed  Google Scholar 

  63. Griffith, D. P. et al. Randomized, double-blind trial of Lithostat (acetohydroxamic acid) in the palliative treatment of infection-induced urinary calculi. Eur. Urol. 20, 243–247 (1991).

    Article  CAS  PubMed  Google Scholar 

  64. Grases, F., Costa-Bauza, A. & Prieto, R. M. Renal lithiasis and nutrition. Nutr. J. 6, 23 (2006).

    Article  CAS  Google Scholar 

  65. Curhan, G. C., Willett, W. C., Speizer, F. E. & Stampfer, M. J. Beverage use and risk for kidney stones in women. Ann. Intern. Med. 128, 534–540 (1998).

    Article  CAS  PubMed  Google Scholar 

  66. Sampath, A., Kossoff, E. H., Furth, S. L., Pyzik, P. L. & Vining, E. P. Kidney stones and the ketogenic diet: risk factors and prevention. J. Child. Neurol. 22, 375–378 (2007).

    Article  PubMed  Google Scholar 

  67. Sarica, K., Eryildirim, B., Yencilek, F. & Kuyumcuoglu, U. Role of overweight status on stone-forming risk factors in children: a prospective study. Urology 73, 1003–1007 (2009).

    Article  PubMed  Google Scholar 

  68. Guan, N. et al. Melamine-contaminated powdered formula and urolithiasis in young children. N. Engl. J. Med. 360, 1067–1074 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Zhang, X. et al. Melamine-induced infant urinary calculi: a report on 24 cases and a 1-year follow-up. Urol. Res. 38, 391–395 (2010).

    Article  PubMed  Google Scholar 

  70. Liu, J. M. et al. Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: a population-based screening and follow-up study. CMAJ 182, 439–443 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Daneman, A. et al. Renal pyramids: focused sonography of normal and pathologic processes. Radiographics 30, 1287–1307 (2010).

    Article  PubMed  Google Scholar 

  72. Hoppe, B. & Kemper, M. J. Diagnostic examination of the child with urolithiasis or nephrocalcinosis. Pediatr. Nephrol. 25, 403–413 (2010).

    Article  PubMed  Google Scholar 

  73. McNally, M. A., Pyzik, P. L., Rubenstein, J. E., Hamdy, R. F. & Kossoff, E. H. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics 124, 300–304 (2009).

    Article  Google Scholar 

  74. Alon, U. S. Medical treatment of pediatric urolithiasis. Pediatr. Nephrol. 24, 2129–2135 (2009).

    Article  PubMed  Google Scholar 

  75. Alon, U. S., Costanzo, L. S. & Chan, J. C. Additive hypocalciuric effects of amiloride and hydrochlorothiazide in patients treated with calcitriol. Miner. Electrolyte Metab. 10, 379–386 (1984).

    CAS  PubMed  Google Scholar 

  76. Odvina, C. V. Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin. J. Am. Soc. Nephrol. 1, 1269–1274 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Kurtz, M. P. & Eisner, B. H. Dietary therapy for patients with hypocitraturic nephrolithiasis. Nat. Rev. Urol. 8, 146–152 (2011).

    Article  CAS  PubMed  Google Scholar 

  78. Milliner, D. Treatment of the primary hyperoxalurias: a new chapter. Kidney Int. 70, 1198–1200 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Jiang, J. et al. Impact of dietary calcium and oxalate, and Oxalobacter formigenes colonization on urinary oxalate excretion. J. Urol. 186, 135–139 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kavukçu, S. et al. Combined liver-kidney transplantation and follow-up in primary hyperoxaluria treatment: report of three cases. Transplant. Proc. 40, 316–319 (2008).

    Article  PubMed  Google Scholar 

  81. Curhan, G. C., Willett, W. C., Rimm, E. B. & Stampfer M. J. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N. Engl. J. Med. 328, 833–838 (1993).

    Article  CAS  PubMed  Google Scholar 

  82. Jaeger, P., Portmann, L., Saunders, L., Rosenberg, L. E. & Thier S. O. Anticystinuric effects of glutamine and of dietary sodium restriction. N. Engl. J. Med. 315, 1120–1123 (1986).

    Article  CAS  PubMed  Google Scholar 

  83. Printza, N., Koukourgianni, F., Papathanasiou, A., Augoustides-Savvopoulou, P. & Papachristou, F. Efficacy of captopril therapy in cystinuria lithiasis. A case report. Hippokratia 11, 83–85 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Brikowski, T. H., Lotan, Y. & Pearle, M. S. Climate-related increase in the prevalence of urolithiasis in the United States. Proc. Natl Acad. Sci. USA 15, 9841–9846 (2008).

    Article  Google Scholar 

  85. Matos, V., Van Melle, G., Werner, D., Bardy, D. & Guignard, J. P. Urinary oxalate and urate to creatinine ratios in a healthy pediatric population. Am. J. Kidney Dis. 34, e1 (1999).

    Article  CAS  PubMed  Google Scholar 

  86. Matos, V. et al. Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J. Pediatr. 131, 252–257 (1997).

    Article  CAS  PubMed  Google Scholar 

  87. Habbig, S., Beck, B. B. & Hoppe, B. Nephrocalcinosis and urolithiasis in children. Kidney Int. 80, 1278–1291 (2011).

    Article  PubMed  Google Scholar 

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F. Baştuğ conducted the research for the article, wrote the article and contributed to the discussion of content. R. Düşünsel contributed to the discussion of content and reviewed the manuscript before submission.

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Correspondence to Funda Baştuğ.

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Baştuğ, F., Düşünsel, R. Pediatric urolithiasis: causative factors, diagnosis and medical management. Nat Rev Urol 9, 138–146 (2012). https://doi.org/10.1038/nrurol.2012.4

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