Background Kidney fibrosis has been reported to be a prognostic factor in CKD progression. Previous studies have shown that the assessment of urinary Dickkopf-3 (uDKK3), a stress induced tubular epithelial-derived profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and might identify patients at short-term risk of eGFR loss. We aim to evaluate uDKK3 as a potential biomarker for progression of CKD in a cohort with various etiologies of CKD, and subsequently in an overt diabetic nephropathy cohort. Methods We prospectively studied two independent cohorts comprising a total of 351 patients with stage 2-3 CKD. Combined primary outcome consisted of a 50% increase in serum creatinine, ESKD or death. Progreser cohort included patients with heterogeneous etiologies and Pronedi cohort 101 patients with overt diabetic nephropathy. Median time of follow-up was 36 (30-39) and 36 (16-48) months, respectively. Results At baseline, median uDKK3 was 2200 (671 - 7617) pg/mg in the Progreser cohort and 3042 (661-9747) pg/mg in the Pronedi cohort. There were any statically significant differences in uDKK3 ratio between both cohorts, nor between CKD etiologies. Baseline uDKK3 was significantly higher in patients who reached primary outcome. In the Cox proportional-hazard model, the highest levels of uDKK3 were found to be an independent factor for renal progression in Progreser cohort (HR 1.91, CI95% 1.04 - 3.52) and in Pronedi cohort (HR 3.03, CI95% 1.03-8.92). uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with RAAS-blockers did not modify uDKK3 after 4 nor 12 months of treatment. Conclusions uDKK3 identifies patients at high risk of CKD progression regardless of the cause of kidney injury. uDKK3 might serve as a useful biomarker for kidney disease progression and therefore could be used by clinicians to optimize staging for renal progression and monitor the response to potential treatments.

Click https://wileyhealthlearning.com/#/online-courses/fa17d935-09f2-4f58-bfeb-5c50a3dda900 for the corresponding questions to this CME article.