High urinary excretion of kidney injury molecule-1 is an independent predictor of graft loss in renal transplant recipients.
BACKGROUND
Chronic transplant dysfunction is characterized by renal function decline and proteinuria. Kidney injury molecule (KIM)-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but markedly induced after injury. Urinary KIM-1 excretion has been quantified as biomarker of renal damage. We prospectively studied whether urinary KIM-1 predicts graft loss, independent of renal function and proteinuria.


METHODS
Renal transplant recipients (n=145) visiting our outpatient clinic between August 2001 and July 2003 collected 24-hour urine samples for assessment of baseline urinary KIM-1 excretion (microsphere-based Luminex technology), and were followed for graft loss.


RESULTS
Recipients participated at a median (interquartile range) of 6.0 (2.5-12.0) years posttransplant in baseline measurements. Follow-up beyond baseline was 4.0 (3.2-4.5) years. Urinary KIM-1 excretion was 0.72 (0.42-1.37) ng per 24 hours. Occurrence of graft loss increased over tertiles of KIM-1 excretion: 3 (6.3%), 11 (22.4%), and 17 cases (35.4%; P=0.001), respectively. High KIM-1 excretion was associated with proteinuria, low creatinine clearance, and high donor age (all P<0.01). In multivariate Cox regression analyses, prediction of graft loss by KIM-1 appeared independent of creatinine clearance, proteinuria, and donor age. Hazard ratios (95% CI) for the second and third tertile of KIM-1 excretion were 3.6 (0.9-13.5) and 5.1 (1.5-17.8) in the final model.


CONCLUSIONS
Urinary excretion of KIM-1 is an independent predictor of long-term graft loss and therefore a promising new biomarker in early prediction of graft loss.
van Timmeren
Mirjan M
MM
Department of Pathology and Laboratory Medicine, University Medical Center Groningen and University of Groningen, the Netherlands. m.m.van.timmeren@path.umcg.nl
Vaidya
Vishal S
VS
van Ree
Rutger M
RM
Oterdoom
Leendert H
LH
de Vries
Aiko P J
AP
Gans
Reinold O B
RO
van Goor
Harry
H
Stegeman
Coen A
CA
Bonventre
Joseph V
JV
Bakker
Stephan J L
SJ
D000328:Adult; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality / Q000473:pathology* / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011507:Proteinuria; D011991:Receptors, Virus; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure
D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D003404:Creatinine