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Abstract: FR-PO130

Chemokine Ligand 14 Could Be a Possible Biomarker of CKD Progression

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Lee, Sunhwa, Seoul National University Hospital, Jongno-gu, SEOUL, Korea (the Republic of)
  • Kim, Yong Chul, Seoul National University Hospital, Jongno-gu, SEOUL, Korea (the Republic of)
  • Yu, Mi-yeon, Seoul National University Hospital, Jongno-gu, SEOUL, Korea (the Republic of)
  • Lee, Hajeong, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Han, Seung Seok, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Jung Pyo, Seoul National University Boramae Medical Center, Seoul, Korea (the Republic of)
  • Cha, Ran-hui, National Medical Center, Seoul, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, SEOUL, Korea (the Republic of)
  • Jeon, Un Sil, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates
  • Kim, Kyu hong, Seoul National University Hosptial, Gyeonggi, Korea (the Republic of)
  • Lee, Jae Wook, National Cancer Center, 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)
Background

Chemokine ligand 14 (CCL14), a ligand for CCR1, has been known as a M2 polarizing marker and chemotactic cytokine, which is expressed by fibroblast, monocyte, etc. Although it was first isolated from the hemofiltrate of chronic renal failure patients, its expression pattern in chronic kidney disease have never been investigated.

Methods

To elucidate concentration change of CCL14 in chronic kidney disease, we performed urine proteomic analysis using three patients’ random urine per each CKD1 and 5. For validating tissue expression of CCL14, kidney biopsy tissues of three normal, nine CKD 3, and eight CKD 5 patients were evaluated by immunohistochemistry. Among CKD 3 group, patients with GFR decrease more than 5 ml/min/1.73 m2 within a year were considered to have rapid progression. We also evaluated kidney tissue expression of CCL14 in acute tubular necrosis that is a well-known etiology of chronic kidney disease if it recurs frequently. For in vitro study, primary cultured human tubular epithelial cells (hTECs) and glomerular endothelial cells (GECs) were treated with rTGFβ for inducing fibrosis, and CCL14 expression level was measured using western blotting.

Results

In urine proteomics analysis, we discovered CCL14 showed a 122-fold increase in CKD 5 patients’ urine comparing to CKD 1 (p<0.001). In other hands, in human kidney biopsy tissue, CKD 3 patients with rapid progression showed higher expression level of CCL14 (17.33±4.13) compared to non-progressive CKD 3 (10.12±3.60) (p=0.032), control (12.48±2.49) (p=0.019), and CKD 5 (9.63±5.52) (p=0.049). CRP was adversely lower in progressive CKD 3 patients compared to others (p=0.017), and interstitial inflammation or fibrosis pattern was not different (p=0.861). In kidney tissue of patients with acute tubular necrosis, CCL14 expression level was 1.6-fold higher than those of normal cases (p=0.015). In in vitro assay, CCL14 expression was increased 2 folded by treating rTGFβ in GEC cells.

Conclusion

CCL14 expression tends to increase in patients with progressive CKD or acute tubular necrosis. Moreover, its expression is increased by a rTGFβ-enriched fibrotic environment. Our results suggest CCL14 could be a possible biomarker of CKD progression that pre-existing inflammatory marker or pathologic variables could not predict.