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Abstract: FR-PO438

Urinary Exosomal CCL21 mRNA as Biomarker of Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Feng, Ye, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIangSu, China
  • Lv, Linli, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIangSu, China
  • Zhong, Xin, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIangSu, China
  • Liu, Bi-Cheng, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIangSu, China
Background

Diabetic nephropathy (DN) is one of the common complications of diabetes characterized by variable histological changes and clinical course. Currently, renal biopsy and pathological assessment remains the standard approach in the diagnosis and prognosis of DN. Given the invasive procedures and unpredictable post-operative complications of biopsy, novel and noninvasive biomarkers are needed. We aimed to find noninvasive biomarkers reflecting the histological injury and progression of renal function in DN.

Methods

A screening cohort of 4 biopsy-proven DN patients and 4 diabetic patients with normal renal function(DM) and a validation cohort of patients with 28 biopsy-proven DN patients and 24 DM patients were enrolled in our study. We isolated exosomes from urine samples at the time of renal biopsy. Urinary exosomes was identified by Western blotting (using Alix, CD63 and CD9 as exosomal markers). Kidney histological damage of DN patients was scored according to Tervaet standard.Urinary exosome profile of the packing inflammatory response related genes were assessed and its correlation with clinic and histological injury parameters were analyzed.

Results

Known exosome markers including Alix, CD63 and CD9 were identified by Western blotting. Profile of the packing inflammatory related mRNA revealed CCL-21 was remarkably upregulated in urinary exosomes of DN patients compared with DM patients(p<0.05). Validation study confirmed the findings and found the correlation of CCL-21 with levels of proteinuria (r=0.590, p<0.05) and eGFR (r=0.591, p<0.05). Furthermore, CCL21 was positively correlated with tubulointerstitial damage. DN patients with severe tubulointerstitial damge showed the highest expression of CCL-21 compared with DN patients with mild and moderate damage. Impressively, CCL21 showed good performance in discriminating patients with different levels of tubulointersitial inflammation.

Conclusion

In summary, urinary exosomal CCL-21 mRNA may be promising noninvasive biomarkers of diabetic nephropathy reflecting renal histological injury and renal function deterioration.