Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes.
OBJECTIVE
To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis.


METHODS
A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-1), liver-type fatty acid-binding protein (uL-FABP), and neutrophil gelatinase associated lipocalin (uNGAL) were determined by enzyme-linked immunosorbent assay (ELISA). After 1 year of follow-up, the predictive values of biomarker panel for determining the prognosis of obstructive nephropathy were evaluated.


RESULTS
uKIM-1 (r = 0.823), uL-FABP (r = 0.670), and uNGAL (r = 0.720) levels were positively correlated with the serum creatinine level (all P<0.01). The levels of uKIM-1, uL-FABP, and uNGAL were higher in the renal function deterioration group than in the renal function stable group. Cox regression analysis revealed that the 72-h postoperative uKIM-1 level and the preoperative and 72-h postoperative uL-FABP levels were all risk factors for renal function deterioration (all P<0.01). The area under the curve of Receiver Operating Characteristic(ROC-AUCs) of 72-h postoperative uKIM-1, preoperative uL-FABP, and 72-h postoperative uL-FABP were 0.786, 0.911, and 0.875, respectively. When the combined preoperative uKIM-1, uL-FABP, and uNGAL levels or combined 72-h postoperative uKIM-1, uL-FABP, and uNGAL levels were considered, the accuracy of prediction for renal prognosis was markedly increased, with an ROC-AUC of 0.967 or 0.964, respectively. Kaplan-Meier survival curve analysis demonstrated that a 72-h postoperative uKIM-1>96.69 pg/mg creatinine (Cr), a preoperative uL-FABP>154.62 ng/mg Cr, and a 72-h postoperative uL-FABP>99.86 ng/mg Cr were all positively correlated with poor prognosis (all P<0.01).


CONCLUSIONS
Biomarker panel may be used as a marker for early screening of patients with obstructive nephropathy and for determining poor prognosis.
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Yuanyuan
Y
Xie
Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Wei
W
Xue
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Xinghua
X
Shao
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Xiajing
X
Che
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Weijia
W
Xu
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Zhaohui
Z
Ni
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Shan
S
Mou
D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000652:urine*; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D011991:Receptors, Virus; D012307:Risk Factors; D014517:Ureteral Obstruction / Q000150:complications* / Q000601:surgery
D000209:Acute-Phase Proteins; D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine