Day-to-day variation of the kidney proximal tubular injury markers urinary cystatin C, KIM1, and NGAL in patients with chronic kidney disease

Ren Fail. 2020 Nov;42(1):400-404. doi: 10.1080/0886022X.2020.1757463.

Abstract

Background: It is important to know the intraindividual variation of biomarkers to be able to distinguish a change of a biomarker due to the course of the disease from the normal biological variation of the marker. The purpose of this study was to investigate the day-to-day variability of urine markers in nephrology patients.Materials: 23 nephrology patients were included in the study. First morning urine samples were collected daily for ten consecutive days and analyzed for U-cystatin C, U-KIM1, U-NGAL and U-creatinine. The day-to-day variation was calculated as concentrations of the markers and as creatinine ratios. Values deviating more than the 90th percentile of the normal intraindividual variation was used to define a disease/treatment specific change.Results: The day-to-day coefficient of variation (CV) for individual patients varied between 9.6 and 100.3% for NGAL (mean 45.6%) and between 8.8 and 107.3% for the NGAL/creatinine ratio (mean 43.8%). The corresponding values for KIM1 were between 10.9 and 60.2% (mean 30.1%) and for the ratio between 8.7 and 59.8% (mean 23.4%) and for cystatin C 3.8-67.4% (mean 25.0%) and for the cystatin C/creatinine ratio 5.9-78.4% (mean 24.8%).Conclusions: The similar intraindividual CV values between the renal tubules damage markers and their corresponding creatinine ratios speaks against using creatinine ratio. Using the 90th percentiles of the CV values as a limit for clinical change means that NGAL has to change by 83.3%, KIM1 by 45.5% and Cystatin C by 46.3% before the change can be considered clinically significant in patients with chronic kidney disease.

Keywords: Day-to-day variation; U-KIM1; U-NGAL; U-cystatin C; proximal tubular injury markers.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Creatinine / urine
  • Cystatin C / urine*
  • Female
  • Hepatitis A Virus Cellular Receptor 1 / analysis*
  • Humans
  • Kidney Tubules / pathology*
  • Lipocalin-2 / urine*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / pathology*
  • Renal Insufficiency, Chronic / urine
  • Sweden

Substances

  • Biomarkers
  • Cystatin C
  • Hepatitis A Virus Cellular Receptor 1
  • Lipocalin-2
  • Creatinine