Urinary Dickkopf-3: a new biomarker for CKD progression and mortality.

Kidney fibrosis has been reported to be a prognostic factor in chronic kidney disease (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 glomerular filtration rate loss. We aim to evaluate uDKK3 as a potential biomarker for progression of CKD in a cohort with various aetiologies of CKD and subsequently in an overt diabetic nephropathy cohort. We prospectively studied two independent cohorts comprising a total of 351 patients with Stages 2 and 3 CKD. Combined primary outcome consisted of a 50% increase in serum creatinine, end-stage kidney disease or death. The Progreser cohort included patients with heterogeneous aetiologies and the Pronedi cohort (101 patients) with overt diabetic nephropathy. The median follow-up time was 36 months [interquartile range (IQR) 30-39] and 36 (16-48), respectively. At baseline, median uDKK3 was 2200 pg/mg (IQR 671-7617) in the Progreser cohort and 3042 pg/mg (IQR 661-9747) in the Pronedi cohort. There were no statistically significant differences in the uDKK3 ratio between both cohorts nor between CKD aetiologies. Baseline uDKK3 was significantly higher in patients who reached the primary outcome. In the Cox proportional hazards model, the highest levels of uDKK3 were found to be an independent factor for renal progression in the Progreser cohort {hazard ratio [HR] 1.91 [95% confidence interval (CI) 1.04-3.52]} and in the Pronedi cohort [HR 3.03 (95% CI 1.03-8.92)]. uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with renin-angiotensin-aldosterone system blockers did not modify uDKK3 after 4 or 12 months of treatment. 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.

Sánchez-Álamo B ，García-Iñigo FJ ，Shabaka A ，Acedo JM ，Cases-Corona C ，Domínguez-Torres P ，Diaz-Enamorado Y ，Landaluce E ，Navarro-González JF ，Gorriz JL ，Martínez-Castelao A ，Fernández-Juárez G ... -  《-》

Urinary Dickkopf 3 Is Not an Independent Risk Factor in a Cohort of Kidney Transplant Recipients and Living Donors.

Jehn U ，Altuner U ，Henkel L ，Menke AF ，Strauss M ，Pavenstädt H ，Reuter S ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss.

The individual course of CKD may vary, and improved methods for identifying which patients will experience short-term eGFR loss are needed. Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia-derived profibrotic glycoprotein, may provide information about ongoing tubulointerstitial fibrosis and short-term eGFR loss. To investigate urinary DKK3's potential as a biomarker of short-term eGFR loss (over 12 months), we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of various etiologies at baseline and annual follow-ups. We also measured urinary DKK3 in a general population sample and patients with diagnostic kidney biopsies or IgA nephropathy under treatment. Median urinary DKK3-to-creatinine concentration at baseline was significantly higher in patients with CKD than the general population sample (431 versus 33 pg/mg). In the CKD cohort, having a urinary DKK3-to-creatinine level >4000 pg/mg was independently and significantly associated after multiple adjustments with mean annual decline in eGFR of 7.6% over 12 months. Urinary DKK3 significantly improved prediction of kidney function decline compared with eGFR or albuminuria alone. Urinary DKK3-to-creatinine levels were related to the extent of tubulointerstitial fibrosis in kidney biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated with significant eGFR decline within 6 months, whereas stable or decreasing urinary DKK3 indicated a more favorable course. Urinary DKK3 levels identify patients at high risk for eGFR decline over the next 12 months regardless of the cause of kidney injury and beyond established biomarkers, potentially providing a tool to monitor CKD progression and assess effects of interventions.

Zewinger S ，Rauen T ，Rudnicki M ，Federico G ，Wagner M ，Triem S ，Schunk SJ ，Petrakis I ，Schmit D ，Wagenpfeil S ，Heine GH ，Mayer G ，Floege J ，Fliser D ，Gröne HJ ，Speer T ... -  《-》

Urinary Dickkopf-3 (DKK3) Is Associated with Greater eGFR Loss in Patients with Resistant Hypertension.

Schäfer AC ，Pieper D ，Dihazi H ，Dihazi GH ，Lüders S ，Koziolek MJ ，Wallbach M ... -  《Journal of Clinical Medicine》

DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease.

Arjune S ，Späth MR ，Oehm S ，Todorova P ，Schunk SJ ，Lettenmeier K ，Chon SH ，Bartram MP ，Antczak P ，Grundmann F ，Fliser D ，Müller RU ... -  《-》