Kidney Week

Abstract: FR-PO0382

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

Session Information

• AKI: Biomarkers, Diagnostics, and Risk Prediction
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Sekiguchi, Momoko, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Momoko Sekiguchi, MD

• Abe, Erika, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Erika Abe, MD

• Okada, Mari, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Mari Okada, MD

• Takayanagi, Kaori, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Kaori Takayanagi, MSc

• Nagayama, Izumi, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Izumi Nagayama, MD

• Takahashi, Shunsuke, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Shunsuke Takahashi, MD, PhD

• Maeshima, Akito, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Akito Maeshima, MD, PhD

Background

The WNT/β-catenin signaling pathway is reactivated following kidney injury and promotes renal fibrosis. Dickkopf-3 (DKK-3) is a stress-induced secreted glycoprotein produced by renal tubular epithelial cells that modulates WNT/β-catenin signaling. Previous studies suggest that DKK-3 reflects tubular stress and contributes to maladaptive repair and fibrogenesis. Although urinary DKK-3 has been reported to be elevated in acute kidney injury and chronic kidney disease, its role in tubulointerstitial nephritis (TIN) remains unclear. Because TIN is characterized by tubular injury and interstitial inflammation, biomarkers reflecting disease activity and treatment response are clinically needed. This study aimed to evaluate urinary DKK-3 as a biomarker of tubular injury and disease activity in TIN.

Methods

We enrolled 21 patients with biopsy-proven TIN and 15 healthy controls. Urinary and serum DKK-3 levels were measured by ELISA. Associations between urinary DKK-3 and renal function parameters, urinary protein, and tubular injury markers (NGAL, β2-microglobulin, KIM-1, and NAG) were analyzed using nonparametric methods. Immunohistochemical analyses of kidney biopsy specimens were performed to determine the localization of DKK-3. Changes in urinary DKK-3 levels following immunosuppressive therapy were also evaluated.

Results

Urinary DKK-3 levels were almost undetectable in healthy controls but were significantly higher in TIN patients (1.02 ± 0.06 ng/mL vs. 25.3 ± 7.49, p<0.001). Urinary DKK-3 levels correlated significantly with urinary protein and NGAL, but not with serum creatinine, eGFR, BUN, KIM-1, NAG, or CRP. No correlation was observed between urinary and serum DKK-3 levels, suggesting a renal, rather than systemic, origin. Immunohistochemistry revealed no detectable DKK-3 expression in normal kidneys, whereas marked expression was observed in TIN specimens. DKK-3 was localized not only in megalin-positive proximal tubular epithelial cells but also in infiltrating CD68-positive macrophages within the interstitium. In most patients, urinary DKK-3 levels significantly decreased following immunosuppressive therapy.

Conclusion

Urinary DKK-3 is markedly elevated in TIN and reflects both tubular injury and interstitial inflammation. It may serve as a noninvasive biomarker for assessing disease activity and treatment response in TIN.