Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis

Clin Exp Nephrol. 2018 Feb;22(1):133-141. doi: 10.1007/s10157-017-1436-3. Epub 2017 Jun 26.

Abstract

Background: To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis.

Methods: Seventy children [36 girls, mean age: 7.3 ± 5.0 years (0.5-18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5 ± 3.8 years (0.9-16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured.

Results: Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2 years of age (p = 0.011, p = 0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n = 6, p = 0.031 and 0.023, respectively).

Conclusions: The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

Keywords: Biomarkers; Kidney injury molecule-1; Kidney stone disease; Metabolic abnormalities; N-acetyl-β-glucosaminidase; Neutrophil gelatinase-associated lipocalin.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Anthropometry
  • Biomarkers / urine*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Follow-Up Studies
  • Hepatitis A Virus Cellular Receptor 1 / analysis
  • Humans
  • Hydronephrosis / etiology
  • Infant
  • Kidney Tubules / pathology*
  • Lipocalin-2 / urine
  • Male
  • Neoplasm Proteins / urine
  • Prospective Studies
  • Risk Factors
  • Urolithiasis / complications*
  • Urolithiasis / pathology
  • Urolithiasis / urine*

Substances

  • Biomarkers
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • LCN2 protein, human
  • Lipocalin-2
  • NBAS protein, human
  • Neoplasm Proteins