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Kidney Week

Abstract: SA-PO116

Dickkopf-3, a Key Driver of Renal Fibrosis, Is Increased in the Urine of Patients with AKI

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Sekiguchi, Momoko, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  • Hamada, Takayuki, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  • Nagayama, Izumi, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  • Takayanagi, Kaori, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  • Hasegawa, Hajime, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  • Maeshima, Akito, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
Background

The WNT–β-catenin system, an evolutionary conserved signaling pathway involved in morphogenesis and cell organization during embryogenesis, is usually suppressed in adulthood but can be re-activated in organ injury and regeneration. Dickkopf (DKK) proteins serve as inhibitors of WNT–β-catenin signaling. Animal models showed that DKK-3 is released by ‘stressed’ tubular epithelial cells and drives kidney fibrosis. However, the role of DKK-3 in human acute kidney injury (AKI) remains unknown. In the present study, we measured urinary DKK-3 in patients with AKI to test if urinary DKK-3 is useful to monitor the degree of tubular damage and/or recovery in human AKI.

Methods

AKI patients (n=66) who were treated in our department (December 2020 to December 2022) and healthy adults (n=16) were enrolled in this study. Written informed consent was obtained from all patients. Serum and urinary DKK-3 were measured by ELISA. The correlation of urinary DKK-3 with renal function, urinary protein level, clinical parameters and various AKI biomarkers were analyzed. This study was approved by the Ethics Committee on Human Research of our institutions (Approval number 2487).

Results

Compared to healthy subjects, urinary DKK-3 was significantly increased in AKI (1.02 ± 0.06 vs. 10.5 ± 1.26 ng/mL, p<0.001). There was no significant difference in urinary DKK-3 level between prerenal and renal AKI, but there was a significant increase according to the stage of AKI. There is a significant correlation of urinary DKK-3 with serum creatinine level, eGFR, urinary NGAL, and urinary beta2-microglobulin, but not with urinary protein level, urinary KIM1, or urinary NAG. Among the causes of AKI, urinary DKK-3 was markedly increased in patients with microscopic polyangiitis, in which urinary DKK-3 was significantly decreased after therapeutic intervention. In cases of kidney transplantation recipients, urinary DKK-3 was markedly increased at 1 day after transplantation but was decreased and became undetectable thereafter.

Conclusion

Urinary DKK-3 might be useful as a marker reflecting tubular damage as well as interstitial fibrosis in patients with AKI.