Kidney injury molecule-1 is an early noninvasive indicator for donor brain death-induced injury prior to kidney transplantation

Am J Transplant. 2009 Aug;9(8):1752-9. doi: 10.1111/j.1600-6143.2009.02713.x. Epub 2009 Jun 12.

Abstract

With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Biopsy
  • Brain Death / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Disease Models, Animal
  • Female
  • Graft Survival / physiology
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Transplantation / physiology*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Predictive Value of Tests
  • Rats
  • Rats, Inbred F344
  • Receptors, Virus / metabolism*
  • Regression Analysis
  • Tissue and Organ Procurement*

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • HAVCR1 protein, human
  • Havcr1protein, rat
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Receptors, Virus