Urinary expression of kidney injury markers in renal transplant recipients.
OBJECTIVE
The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. We examined whether urinary expression of specific biomarker mRNA could be used as a noninvasive prognostic marker in kidney transplant recipients.


METHODS
We studied 63 kidney transplant recipients who require graft biopsy because of progressive worsening of kidney function. The mRNA of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 (KIM-1), IL-18, surfactant protein-C, and S100 calcium-binding proteins A8 and A9 in urinary sediment were quantified.


RESULTS
Urinary expressions of neutrophil gelatinase-associated lipocalin, KIM-1, and IL-18, but not other target genes, were significantly different between histologic groups (P < 0.0001 for all). After followed for an average of 39.7 ± 21.1 months, the rate of renal function decline significantly correlated with urinary KIM-1 expression (r = -0.434, P = 0.0004) but not other target genes. At 48 months, the graft survival rate for the high and low KIM-1 groups were 46.2 and 78.6%, respectively. After adjusting for confounding variables, each log of higher urinary KIM-1 expression conferred an ~2.9-fold higher risk of developing graft failure (95% confidence interval, 1.3- to 6.2-fold; P = 0.006). The result remained similar when only patients with no acute cellular rejection were analyzed.


CONCLUSIONS
In kidney allograft recipients, urinary KIM-1 expression provides prognostic information in relation to the rate of renal function decline, irrespective of the kidney pathology.
Szeto
Cheuk-Chun
CC
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. ccszeto@cuhk.edu.hk
Kwan
Bonnie Ching-Ha
BC
Lai
Ka-Bik
KB
Lai
Fernand Mac-Moune
FM
Chow
Kai-Ming
KM
Wang
Gang
G
Luk
Cathy Choi-Wan
CC
Li
Philip Kam-Tao
PK
D058186:Acute Kidney Injury / Q000175:diagnosis / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D040501:Calgranulin A / Q000235:genetics; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D016030:Kidney Transplantation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus
D000209:Acute-Phase Proteins; D015415:Biomarkers; D040501:Calgranulin A; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; D011991:Receptors, Virus; C489679:SFTPC protein, human