Adolescents with urinary stones have elevated urine levels of inflammatory mediators
Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins. To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Macrophage inflammatory protein 1β and interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated in urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, macrophage inflammatory protein 1β and interleukin 13 represent investigative targets.
KeywordsInnate immunity Cytokine Biomarker Interleukin
This study was funded by intramural funds from The Research Institute at Nationwide Children’s Hospital and Indiana University (Grant no. intramural funds).
Compliance with ethical standards
Conflict of interest
Andrew Schwaderer has received funds for consulting for Allena Pharmaceuticals on a topic unrelated to this manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written informed consent and (for minors) written informed assent was obtained from all individual participants included in the study.
- 1.Tasian GE, Ross ME, Song L, Sas DJ, Keren R, Denburg MR, Chu DI, Copelovitch L, Saigal CS, Furth SL (2016) Annual incidence of nephrolithiasis among children and adults in South Carolina from 1997 to 2012. Clin J Am Soc Nephrol 11(3):488–496. https://doi.org/10.2215/CJN.07610715 CrossRefGoogle Scholar
- 4.Anderson L, Mc DJ (1946) The origin, frequency, and significance of microscopic calculi in the kidney. Surg Gynecol Obstet 82:275–282Google Scholar
- 16.Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, Muruve D, Shi Y, Munro F, Liapis H, Anders HJ (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Investig 123(1):236–246. https://doi.org/10.1172/JCI63679 CrossRefGoogle Scholar
- 17.World Health Organization (1995) Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 854:1–452Google Scholar
- 19.Khanna M, Sromath D, Mendirata D (2015) The study of obesity in children using fuzzy logic. IJITR 3:1833–1836Google Scholar
- 23.Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, Muruve D, Shi Y, Munro F, Liapis H, Anders HJ (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J Clin Investig 123(1):236–246. https://doi.org/10.1172/JCI63679 CrossRefGoogle Scholar
- 24.Allen SJ, Crown SE, Handel TM (2007) Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 25:787–820. https://doi.org/10.1146/annurev.immunol.24.021605.090529 CrossRefGoogle Scholar
- 33.Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Zhang Y, Elias JA (1999) Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Investig 103(6):779–788. https://doi.org/10.1172/JCI5909 CrossRefGoogle Scholar