Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies
Introduction: Phenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein, Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney functio...
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Elsevier
2025-01-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924019521 |
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| author | Mareike Dahmer-Heath Joachim Gerß Danilo Fliser Max Christoph Liebau Thimoteus Speer Anna-Katharina Telgmann Kathrin Burgmaier Petra Pennekamp Lars Pape Franz Schaefer Martin Konrad Jens Christian König |
| author_facet | Mareike Dahmer-Heath Joachim Gerß Danilo Fliser Max Christoph Liebau Thimoteus Speer Anna-Katharina Telgmann Kathrin Burgmaier Petra Pennekamp Lars Pape Franz Schaefer Martin Konrad Jens Christian König |
| author_sort | Mareike Dahmer-Heath |
| collection | DOAJ |
| description | Introduction: Phenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein, Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary DKK3 (uDKK3) levels in 195 pediatric patients with renal ciliopathy to assess its potential as a discriminative and prediction marker. Methods: uDKK3 concentration was measured in 357 spot urine samples from 247 individuals, including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n = 37), autosomal recessive polycystic kidney disease (ARPKD) (n = 61), Bardet Biedl syndrome (BBS) (n = 57), and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n = 40). The results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. Results: Median uDKK3-to-creatinine ratios (uDKK3/crea) in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, P < 0.001): NPH, 1.219 pg/mg; HNF1B, 731 pg/mg; BBS, 541 pg/mg; and ARPKD, 437 pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (P < 0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (P = 0.0029). Although we observed a trend toward lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (P = 0.2637). Conclusion: In renal ciliopathies, uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline. |
| format | Article |
| id | doaj-art-a242189d0c4e407e9ff0bc25b0d68e99 |
| institution | OA Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-a242189d0c4e407e9ff0bc25b0d68e992025-08-20T02:33:34ZengElsevierKidney International Reports2468-02492025-01-0110119720810.1016/j.ekir.2024.09.023Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal CiliopathiesMareike Dahmer-Heath0Joachim Gerß1Danilo Fliser2Max Christoph Liebau3Thimoteus Speer4Anna-Katharina Telgmann5Kathrin Burgmaier6Petra Pennekamp7Lars Pape8Franz Schaefer9Martin Konrad10Jens Christian König11Department of General Pediatrics, University Children's Hospital Münster, Münster, GermanyInstitute of Biostatistics and Clinical Research, University of Münster, Münster, GermanyDepartment of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg/ Saar, GermanyDepartment of Pediatrics, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, Center for Family Health and Center for Rare Disease, University Hospital Cologne and Medical Faculty, University of Cologne, Cologne, GermanyDepartment of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg/ Saar, Germany; Else Kroener Fresenius Center for Nephrological Research, University Hospital Frankfurt, Frankfurt, GermanyDepartment of General Pediatrics, University Children's Hospital Münster, Münster, GermanyDepartment of Pediatrics, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany; Faculty of Applied Healthcare Science, Deggendorf Institute of Technology, Deggendorf, GermanyDepartment of General Pediatrics, University Children's Hospital Münster, Münster, GermanyDepartment of Pediatrics II, University Hospital of Essen, Essen, GermanyDivision of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, GermanyDepartment of General Pediatrics, University Children's Hospital Münster, Münster, GermanyDepartment of General Pediatrics, University Children's Hospital Münster, Münster, Germany; Correspondence: Jens Christian König, Department of General Pediatrics, University Hospital Münster Münster, Nordrhein-Westfalen Germany.Introduction: Phenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein, Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary DKK3 (uDKK3) levels in 195 pediatric patients with renal ciliopathy to assess its potential as a discriminative and prediction marker. Methods: uDKK3 concentration was measured in 357 spot urine samples from 247 individuals, including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n = 37), autosomal recessive polycystic kidney disease (ARPKD) (n = 61), Bardet Biedl syndrome (BBS) (n = 57), and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n = 40). The results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. Results: Median uDKK3-to-creatinine ratios (uDKK3/crea) in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, P < 0.001): NPH, 1.219 pg/mg; HNF1B, 731 pg/mg; BBS, 541 pg/mg; and ARPKD, 437 pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (P < 0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (P = 0.0029). Although we observed a trend toward lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (P = 0.2637). Conclusion: In renal ciliopathies, uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline.http://www.sciencedirect.com/science/article/pii/S2468024924019521DKK3kidney fibrosiskidney function declinepediatric kidney diseasepredictive biomarkerrenal ciliopathies |
| spellingShingle | Mareike Dahmer-Heath Joachim Gerß Danilo Fliser Max Christoph Liebau Thimoteus Speer Anna-Katharina Telgmann Kathrin Burgmaier Petra Pennekamp Lars Pape Franz Schaefer Martin Konrad Jens Christian König Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies Kidney International Reports DKK3 kidney fibrosis kidney function decline pediatric kidney disease predictive biomarker renal ciliopathies |
| title | Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies |
| title_full | Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies |
| title_fullStr | Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies |
| title_full_unstemmed | Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies |
| title_short | Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies |
| title_sort | urinary dickkopf 3 reflects disease severity and predicts short term kidney function decline in renal ciliopathies |
| topic | DKK3 kidney fibrosis kidney function decline pediatric kidney disease predictive biomarker renal ciliopathies |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924019521 |
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