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Abstract: TH-PO880

Soluble cMet Levels in Urine Are a Significant Prognostic Biomarker for Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Kim, Yong Chul, SNUH, Seoul, Korea (the Republic of)
  • An, Jung Nam, Seoul National University Boramae Medical Center, Seoul, SEOUL, Korea (the Republic of)
  • Lim, Chun Soo, Seoul National University Boramae Medical Center, Seoul, SEOUL, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)
  • Lee, Jung Pyo, Seoul National University Boramae Medical Center, Seoul, SEOUL, Korea (the Republic of)
Background

Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Here, we evaluated the clinical role of urinary cMet as prognostic biomarker in diabetic nephropathy (DN).

Methods

A total of 218 patients with DN were enrolled in this study. We examined the association of urine cMet levels and long-term outcomes in patients with DN.

Results

The levels of urinary cMet were higher in patients with decreased renal function than in patients with relatively preserved renal function (5.17 ± 9.56 ng/ml versus 1.86 ± 4.85 ng/ml, P = 0.001). A fully adjusted model revealed that a urinary cMet cutoff of 2.9 ng/mL was associated with a hazard ratio for end-stage renal disease of 2.50 (95% confidence interval 1.18–4.53, P = 0.007). The addition of urinary cMet to serum creatinine and proteinuria provided the highest net reclassification improvement. We found that in primary cultured human glomerular endothelial cells, TGFβ treatment induced fibrosis, and the protein expression levels of collagen IV, fibronectin, and αSMA were decreased after administration of an agonistic cMet antibody.

Conclusion

In conclusion, elevated levels of urinary cMet at the time of initial diagnosis could predict renal outcomes in patients with DN.

Comparison of the ROC curve, IDI and category-free NRI of the Cr vs. Cr, UPCR vs. Cr, UPCR, cMet/Cr in predicting ESRD
 AUC (95% CI)DeLong test
P-value
IDI
P-value
.
(95% CI)
 category-free NRI
P-value
.
(95% CI)
 
ESRD       
Cr
cMet/Cr
Cr+UPCR
Cr+UPCR+cMet/Cr
0.858 (0.808, 0.907)
0.694 (0.623, 0.765)
0.889 (0.846, 0.931)
0.890 (0.848, 0.933)
Reference
<0.0001
0.0389
0.0295
Reference
<0.0001
0.0001
0.0001
.
.
6.52% (3.18%, 9.87%)
6.76% (3.38%, 10.15%)
 Reference
<0.0001
<0.0001
<0.0001
.
.
88.31% (65.02%, 111.61%)
82.64% (59.07%, 106.22%)
Death       
Cr
cMet/Cr
Cr+UPCR
Cr+UPCR+cMet/Cr
0.644 (0.569, 0.720)
0.620 (0.536, 0.704)
0.633 (0.556, 0.710)
0.641 (0.558, 0.724)
Reference
0.5943
0.5717
0.9138
Reference
0.0748
0.4641
0.0372
.
.
0.32% (-0.53%, 1.17%)
2.76% (0.16%, 5.35%)
 Reference
0.1726
0.3923
0.8453
.
.
11.95% (-15.42%, 39.31%)
-2.82% (-31.11%, 25.47%)
Composite       
Cr
cMet/Cr
Cr+UPCR
Cr+UPCR+cMet/Cr
0.865 (0.818, 0.911)
0.694 (0.626, 0.761)
0.878 (0.835, 0.922)
0.886 (0.844, 0.928)
Reference
<0.0001
0.1490
0.0555
Reference
<0.0001
0.0196
0.0005
.
.
2.86% (0.46%, 5.27%)
4.78% (2.10%, 7.46%)
 Reference
<0.0001
<0.0001
<0.0001
.
.
81.06% (57.53%, 104.59%)
74.21% (50.30%, 98.12%)

Cr, creatinine; UPCR, urine protein-to-creatinine ratio; ESRD, end stage renal disease; CI, confidence interval; IDI, integrated discriminatory improvement; NRI, net reclassification improvement