TY - JOUR
T1 - Cystatin C, Neutrophil Gelatinase-associated Lipocalin, and Lysozyme C
T2 - Urinary Biomarkers for Detection of Early Kidney Dysfunction in Children With Urolithiasis
AU - Kovacevic, Larisa
AU - Lu, Hong
AU - Kovacevic, Natalija
AU - Thomas, Ronald
AU - Lakshmanan, Yegappan
N1 - Funding Information:
Financial Disclosures: This research is being funded by the Children's Hospital of Michigan Foundation ( R2-2014-31 ).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9
Y1 - 2020/9
N2 - OBJECTIVE: To screen for the presence of biomarkers involved in tubular injury and kidney damage in children with urolithiasis (RS), and to validate these proteins by ELISA. METHODS: Prospective-controlled pilot study of children with urolithiasis and their age- and gender-matched controls (HC). Initial screening test was done by quantitative proteomic comparison of pooled urine from RS versus HC, using liquid chromatography-mass spectrometry. Proteins of interest were selected using the following criteria: (1) ≥5 spectral counts; (2) ≥2-fold difference in spectral counts; and (3) ≤.05 P value for the Fisher's Exact Test. Validation was performed by ELISA testing. Statistical analysis was performed by Student t-test and Mann-Whitney U test. RESULTS: Proteomic analysis identified 3 proteins of interest, Cystatin C (CYTC), neutrophil gelatinase-associated lipocalin (NGAL) and lysozyme C that were significantly over-represented in RS group versus HC. ELISA analysis revealed significantly increased urinary levels of CYTC and NGAL, and nearly significantly increased urinary levels of lysozyme C in RS group (N = 24) compared to controls (N = 13). Subgroup analysis showed significantly higher urinary levels of CYTC in both hypercalciuria (N = 14) and hypocitraturia (N = 10) versus HC (P <.05). CONCLUSION: Children with urolithiasis showed significant increase in urinary CYTC and NGAL irrespective of their normal serum creatinine. These biomarkers indicate tubular injury and early kidney damage and represent valid tools for early screening when traditional tests are normal.
AB - OBJECTIVE: To screen for the presence of biomarkers involved in tubular injury and kidney damage in children with urolithiasis (RS), and to validate these proteins by ELISA. METHODS: Prospective-controlled pilot study of children with urolithiasis and their age- and gender-matched controls (HC). Initial screening test was done by quantitative proteomic comparison of pooled urine from RS versus HC, using liquid chromatography-mass spectrometry. Proteins of interest were selected using the following criteria: (1) ≥5 spectral counts; (2) ≥2-fold difference in spectral counts; and (3) ≤.05 P value for the Fisher's Exact Test. Validation was performed by ELISA testing. Statistical analysis was performed by Student t-test and Mann-Whitney U test. RESULTS: Proteomic analysis identified 3 proteins of interest, Cystatin C (CYTC), neutrophil gelatinase-associated lipocalin (NGAL) and lysozyme C that were significantly over-represented in RS group versus HC. ELISA analysis revealed significantly increased urinary levels of CYTC and NGAL, and nearly significantly increased urinary levels of lysozyme C in RS group (N = 24) compared to controls (N = 13). Subgroup analysis showed significantly higher urinary levels of CYTC in both hypercalciuria (N = 14) and hypocitraturia (N = 10) versus HC (P <.05). CONCLUSION: Children with urolithiasis showed significant increase in urinary CYTC and NGAL irrespective of their normal serum creatinine. These biomarkers indicate tubular injury and early kidney damage and represent valid tools for early screening when traditional tests are normal.
UR - http://www.scopus.com/inward/record.url?scp=85086929172&partnerID=8YFLogxK
U2 - 10.1016/j.urology.2020.05.050
DO - 10.1016/j.urology.2020.05.050
M3 - Article
C2 - 32505622
AN - SCOPUS:85086929172
VL - 143
SP - 221
EP - 226
JO - Urology
JF - Urology
SN - 0090-4295
ER -