https://doi.org/10.4081/aiua.2025.13954
Urinary biomarker as a predictor of urolithiasis in children: a systematic review and meta-analysis
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 5 August 2025
Introduction: Urolithiasis in children has become a clinical concern because of its longterm impact on kidney function and quality of life. In previous studies, the role of urinary biomarkers in predicting the risk of urolithiasis in children was still unclear due to inconsistent findings. This meta-analysis aimed to evaluate the diagnostic potential of various urinary risk factors in children with urolithiasis.
Methods: A systematic review and meta-analysis was performed based on PRISMA 2020 guidelines, registered in PROSPERO (CRD42025644893). A total of six studies (1 cohort and 5 case-control) involving 2,060 pediatric patients (817 with urolithiasis; 1,243 controls) were analyzed. Urinary risk factors - including citrate/creatinine (Cit/Cr), oxalate/creatinine (Ox/Cr), calcium/creatinine (Ca/Cr), phosphorus/creatinine (P/Cr), magnesium/ creatinine (Mg/Cr), and urea/creatinine (Ur/Cr) - were examined. Standard Mean Differences (SMD) were calculated, and heterogeneity was assessed using the I² statistic.
Results: Significant differences were obtained in the Cit/Cr, Ca/Cr, Ox/Cr, and Mg/Cr ratios between children with urolithiasis and controls. Hypocitraturia (Cit/Cr SMD: -0.60, 95% CI: -0.90 to -0.30, p = 0.0001), hyperoxaluria (Ox/Cr SMD: 0.76, 95% CI: 0.37-1.16, p = 0.0001), hypercalciuria (Ca/Cr SMD: 0.55, 95% CI: 0.10-1.01, p = 0.02), and hypomagnesuria (SMD -0.13 (95% CI: -0.24 to -0.01), p = 0.03) were significantly associated with the formation of stones in the urinary tract. On the contrary, there were no significant relationships for P/Cr and Ur/Cr ratios.
Conclusions: This meta-analysis highlights Cit/Cr, Ox/Cr, and Ca/Cr ratios as potential urinary biomarkers to identify the risk of urolithiasis in pediatric patients. Hypocitraturia, hyperoxaluria, and hypercalciuria are the main metabolic abnormalities that contribute to urinary tract stone formation. Future studies with standardized methodology are essential to confirm these findings and guide clinical management strategies.
Downloads
Murray CJL; GBD 2021 Collaborators. Findings from the Global Burden of Disease Study 2021. Lancet 2024;403:2259-2262.
Copelovitch L. Urolithiasis in children: Medical approach. Pediatr Clin North Am. 2012; 59:881-96.
Sorokin I, Mamoulakis C, Miyazawa K, et al. Epidemiology of stone disease across the world. World J Urol 2017; 35:1301-20.
Coward RJM, Peters CJ, Duffy PG, et al. Epidemiology of paediatric renal stone disease in the UK. Arch Dis Child. 2003; 88:962-5.
Khan SR, Pearle MS, Robertson WG, et al. Kidney stones. Nat Rev Dis Primers. 2016; 2:16008.
Gao H, Lin J, Xiong F, et al. Urinary microbial and metabolomic profiles in kidney stone disease. Front Cell Infect Microbiol. 2022;12:953392.
Duan X, Zhang T, Ou L, et al. 1h nmr-based metabolomic study of metabolic profiling for the urine of kidney stone patients. Urolithiasis. 2020; 48:27-35.
Kovacevic L, Lu H, Kovacevic N, et al. Cystatin c, neutrophil gelatinase-associated lipocalin, and lysozyme c: Urinary biomarkers for detection of early kidney dysfunction in children with urolithiasis. Urology. 2020; 143:221-6.
Tasdemir M, Fuçucuoglu D, Küçük SH, et al. Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis. Clin Exp Nephrol. 2018; 22:133-141.
Kuroczycka-Saniutycz E, Porowski T, Protas PT, et al. Does obesity or hyperuricemia influence lithogenic risk profile in children with urolithiasis? Pediatr Nephrol. 2015; 30:797-803.
Reusz GS, Dobos M, Byrd D, et al. Urinary calcium and oxalate excretion in children. Pediatr Nephrol. 1995; 9:39-44.
Porowski T, Kirejczyk JK, Konstantynowicz J, et al. Correspondence between ca²+ and calciuria, citrate level and ph of urine in pediatric urolithiasis. Pediatr Nephrol. 2013; 28:1079-84.
Tekin A, Tekgul S, Atsu N, et al. A study of the etiology of idiopathic calcium urolithiasis in children: Hypocitruria is the most important risk factor. J Urol. 2000; 164:162-5.
Srivastava T, Alon US. Pathophysiology of hypercalciuria in children. Pediatr Nephrol. 2007; 22:1659-73.
Habbig S, Beck BB, Hoppe B. Nephrocalcinosis and urolithiasis in children. Kidney Int 2011; 80:1278-91.
Tasian GE, Ziemba J, Casale P. Unilateral hypercalciuria: A stealth culprit in recurrent ipsilateral urolithiasis in children. J Urol. 2012; 188:2330-5.
Kamel AS, Al-Gameel A, Mahmoud M, et al. Role of urinary calcium/creatinine ratio in diagnosis of hypercalciuria in children with urolithiasis in Fayoum, Egypt. Al-Azhar J Pediatr 2022;25:3034-3049
Kovacevic L, Wolfe-Christensen C, Edwards L, et al. From hypercalciuria to hypocitraturia--a shifting trend in pediatric urolithiasis? J Urol. 2012; 188:1623-7.
Chung HJ. The role of randall plaques on kidney stone formation. Transl Androl Urol. 2014; 3:251-4.
Malihi Z, Wu Z, Stewart AW, et al. Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin d supplementation:A systematic review and meta-analysis. Am J Clin Nutr. 2016; 104:1039-51.
Peerapen P, Thongboonkerd V. Kidney stone proteomics: An update and perspectives. Expert Rev Proteomics. 2021; 18:557-69.
Sikora P, von Unruh GE, Beck B, et al. [13c2] oxalate absorption in children with idiopathic calcium oxalate urolithiasis or primary hyperoxaluria. Kidney International. 2008; 73:1181-6.
Tekin A, Tekgul S, Atsu N, et al. Ureteropelvic junction obstruction and coexisting renal calculi in children: Role of metabolic abnormalities. Urology 2001;57:542-5.
Yilmaz K, Dorterler ME. Characteristics of presentation and metabolic risk factors in relation to extent of involvement in infants with nephrolithiasis. Euras J Medl Invest 2020;4:78-85.
Issler N, Dufek S, Kleta R, et al. Epidemiology of paediatric renal stone disease: A 22-year single centre experience in the UK. BMC Nephrology. 2017; 18:136.
Placzynska M, Milart J, Lubas A, et al. Association between the metabolic profile of urolithiasis in children with idiopathic hypercalciuria and the composition of the stone assessed by infrared spectroscopy. Polish J Paediatrics 2023; 98:271-7.
Kaestner L, Meki S, Moore A, et al. General and dietary oxalate restriction advice reduces urinary oxalate in the stone clinic setting.S Afr J Surg. 2020; 58:210-2.
Gadiyar N, Geraghty RM, Premakumar Y, Somani BK. Changes in urine composition and risk of kidney stone disease following bariatric surgery: A systematic review over last 2 decades. Curr Urol Rep. 2022; 23:279-95.
Velásquez-Forero F, Esparza M, Salas A, et al. Risk factors evaluation for urolithiasis among children. Bol Med Hosp Infant Mex. 2016; 73:228-36.
Leslie SW, Bashir K. Hypocitraturia and renal calculi. Treasure Island, StatPearls Publishing; 2024.
Tefekli A, Esen T, Ziylan O, et al. Metabolic risk factors in pediatric and adult calcium oxalate urinary stone formers: Is there any difference? Urol Int. 2003;70:273-7.
Lee ST, and Cho H. Metabolic features and renal outcomes of urolithiasis in children. Renal Failure. 2016; 38:927-32.
Kirejczyk JK, Porowski T, Konstantynowicz J, et al. Urinary citrate excretion in healthy children depends on age and gender. Pediatr Nephrol. 2014; 29:1575-82.
Sheng X, Jung T, Wesson JA, Ward MD. Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents. Proc Natl Acad Sci USA 2005;102:267-72.
Krieger NS, Asplin JR, Frick KK, et al. Effect of potassium citrate on calcium phosphate stones in a model of hypercalciuria. J Am Soc Nephrol. 2015; 26:3001-8.
Penido MG, Tavares Mde S. Pediatric primary urolithiasis: Symptoms, medical management and prevention strategies. World J Nephrol. 2015; 4:444-54.
Castellani D, Giulioni C, De Stefano V, et al. Dietary management of hypocitraturia in children with urolithiasis: Results from a systematic review. World J Urol. 2023; 41:1243-50.
Alhamdi MH, Alimah GJ. Low oxalate diet for prevention of kidney stone disease: A literature review. SCRIPTA SCORE Sci Med J. 2024; 6:28-37.
Escribano J, Balaguer A, Roqué i Figuls M, et al. Dietary interventions for preventing complications in idiopathic hypercalciuria. Cochrane Database Syst Rev. 2014;2014:CD006022.
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.