{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:07:29Z","timestamp":1787069249775,"version":"build-2736575974"},"reference-count":53,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB-TRR219"],"award-info":[{"award-number":["SFB-TRR219"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006723","name":"INST","doi-asserted-by":"publisher","award":["256\/538-1"],"award-info":[{"award-number":["256\/538-1"]}],"id":[{"id":"10.13039\/501100006723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Approximately 750 million people worldwide suffer from chronic kidney diseases (CKDs)\u2014a leading cause of cardiovascular morbidity and premature mortality\u2014but early identification of progressive kidney function decline in patients at risk is still a challenge. CKD diagnosis relies on estimated glomerular filtration rate and albuminuria screening, primarily reflecting glomerular injury. Nevertheless, in a substantial proportion of affected subjects progressive CKD initially remains undetected, since kidney function deteriorates through ongoing tubulointerstitial injury without significant albuminuria, a condition known as \u201cnonalbuminuric\u201d CKD.<\/jats:p>\n                  <jats:p>Urinary Dickkopf-3 (uDKK3) has emerged as an innovative biomarker of progressive CKD, which is expressed by proximal tubular epithelial cells as a response to continuing injury. It is secreted into the urine, where it signals ongoing fibrogenic activity within the kidney. Clinical studies across a broad range of CKD etiologies\u2014in adults and children alike\u2014have shown that elevated uDKK3 significantly improved detection and prediction of progressive CKD after adjustment for established CKD risk markers including albuminuria. Moreover, in primarily nonalbuminuric populations, e.g. those with type 2 diabetes and patients with heart or lung diseases, uDKK3 identifies high-risk individuals for future decline of kidney function.<\/jats:p>\n                  <jats:p>These findings support the hypothesis that CKD progression follows different pathways of mainly glomerular or tubulointerstitial injury. It is therefore plausible to use complementary biomarkers for CKD screening\u2014albuminuria and uDKK3\u2013each reflecting a distinct biological dimension of kidney injury. We discuss the limitations of albuminuria screening and propose a framework for integrating tubular markers like uDKK3 into future CKD screening strategies.<\/jats:p>","DOI":"10.1093\/ndt\/gfag166","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:38:16Z","timestamp":1785843496000},"source":"Crossref","is-referenced-by-count":0,"title":["CKD screening: urinary albumin or uDKK3 or both?"],"prefix":"10.1093","author":[{"given":"Stefan","family":"Neuhaus","sequence":"first","affiliation":[{"name":"Clinic for Internal Medicine IV, Saarland University Medical Center , Homburg\/Saar ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8601-2146","authenticated-orcid":false,"given":"Danilo","family":"Fliser","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine IV, Saarland University Medical Center , Homburg\/Saar ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schunk","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine IV, Saarland University Medical Center , Homburg\/Saar ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026081810415773900_bib1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415773900_bib2","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41581-024-00860-y","article-title":"Healthy ageing and the kidney\u2014lessons from centenarians","volume":"20","author":"Arai","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415773900_bib3","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nrneph.2017.52","article-title":"The systemic nature of CKD","volume":"13","author":"Zoccali","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415773900_bib4","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1161\/CIRCULATIONAHA.120.050686","article-title":"Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation"},{"key":"2026081810415773900_bib5","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"2026081810415773900_bib6","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/S2213-8587(15)00094-7","article-title":"Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes","volume":"3","author":"Porrini","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026081810415773900_bib7","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1001\/archinte.168.22.2440","article-title":"Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy: Atherosclerosis Risk in Communities (ARIC) Study","volume":"168","author":"Bash","year":"2008","journal-title":"Arch Intern Med"},{"key":"2026081810415773900_bib8","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1007\/s00125-018-4691-2","article-title":"Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study","volume":"61","author":"Penno","year":"2018","journal-title":"Diabetologia"},{"key":"2026081810415773900_bib9","doi-asserted-by":"publisher","first-page":"775","DOI":"10.2337\/dc17-1954","article-title":"Increasing mortality in adults with diabetes and low estimated glomerular filtration rate in the absence of albuminuria","volume":"41","author":"Kramer","year":"2018","journal-title":"Diabetes Care"},{"key":"2026081810415773900_bib10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.2337\/dc15-0184","article-title":"Progressive renal decline: the new paradigm of diabetic nephropathy in type 1 diabetes","volume":"38","author":"Krolewski","year":"2015","journal-title":"Diabetes Care"},{"key":"2026081810415773900_bib11","doi-asserted-by":"publisher","first-page":"F145","DOI":"10.1152\/ajprenal.00164.2016","article-title":"The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction","volume":"311","author":"Chevalier","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026081810415773900_bib12","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1053\/j.ackd.2016.11.011","article-title":"The tubulointerstitial pathophysiology of progressive kidney disease","volume":"24","author":"Schnaper","year":"2017","journal-title":"Adv Chronic Kidney Dis"},{"key":"2026081810415773900_bib13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41581-024-00907-0","article-title":"Crosstalk between glomeruli and tubules","volume":"21","author":"Fogo","year":"2025","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415773900_bib14","doi-asserted-by":"publisher","first-page":"e84916","DOI":"10.1172\/jci.insight.84916","article-title":"Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis","volume":"1","author":"Federico","year":"2016","journal-title":"JCI Insight"},{"key":"2026081810415773900_bib15","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1681\/ASN.2018040405","article-title":"Dickkopf-3 (DKK3) in urine identifies patients with short-term risk of eGFR loss","volume":"29","author":"Zewinger","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"2026081810415773900_bib16","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/s41581-020-00343-w","article-title":"WNT\u2013\u03b2-catenin signalling\u2014a versatile player in kidney injury and repair","volume":"17","author":"Schunk","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415773900_bib17","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1681\/ASN.2008060566","article-title":"Wnt\/\u03b2-catenin signaling promotes renal interstitial fibrosis","volume":"20","author":"He","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2026081810415773900_bib18","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s00467-013-2733-z","article-title":"Coordination of kidney organogenesis by Wnt signaling","volume":"29","author":"Halt","year":"2014","journal-title":"Pediatr Nephrol"},{"key":"2026081810415773900_bib19","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00424-017-2018-7","article-title":"The hormetic functions of Wnt pathways in tubular injury","volume":"469","author":"Gr\u00f6ne","year":"2017","journal-title":"Pflugers Arch"},{"key":"2026081810415773900_bib20","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/s41467-024-44886-z","article-title":"WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease","volume":"15","author":"Cohen","year":"2024","journal-title":"Nat Commun"},{"key":"2026081810415773900_bib21","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13069-015-0024-y","article-title":"Primary cilia modulate balance of canonical and non-canonical Wnt signaling responses in the injured kidney","volume":"8","author":"Saito","year":"2015","journal-title":"Fibrosis Tissue Repair"},{"key":"2026081810415773900_bib22","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-catenin signaling, disease, and emerging therapeutic modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"2026081810415773900_bib23","doi-asserted-by":"publisher","first-page":"7469","DOI":"10.1038\/sj.onc.1210054","article-title":"Function and biological roles of the Dickkopf family of Wnt modulators","volume":"25","author":"Niehrs","year":"2006","journal-title":"Oncogene"},{"key":"2026081810415773900_bib24","first-page":"1858","article-title":"Downregulation of Dickkopf-3 disrupts prostate acinar morphogenesis through TGF-\u03b2\/Smad signalling","volume":"126","author":"Romero","year":"2013","journal-title":"J Cell Sci"},{"key":"2026081810415773900_bib25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41392-025-02541-z","article-title":"Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis","volume":"11","author":"Li","year":"2026","journal-title":"Signal Transduct Target Ther"},{"key":"2026081810415773900_bib26","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1681\/ASN.2010030237","article-title":"Genetic variation of DKK3 may modify renal disease severity in ADPKD","volume":"21","author":"Liu","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"2026081810415773900_bib27","doi-asserted-by":"publisher","first-page":"sfad262","DOI":"10.1093\/ckj\/sfad262","article-title":"DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease","volume":"17","author":"Arjune","year":"2024","journal-title":"Clin Kidney J"},{"key":"2026081810415773900_bib28","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1073\/pnas.1115980109","article-title":"Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance","volume":"109","author":"Papatriantafyllou","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026081810415773900_bib29","doi-asserted-by":"publisher","first-page":"8642","DOI":"10.1038\/s41598-021-88107-9","article-title":"The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population","volume":"11","author":"Piek","year":"2021","journal-title":"Sci Rep"},{"key":"2026081810415773900_bib30","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1093\/ndt\/gfab198","article-title":"Urinary Dickkopf-3: a new biomarker for CKD progression and mortality","volume":"36","author":"S\u00e1nchez-\u00c1lamo","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2026081810415773900_bib31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/S2352-4642(23)00049-4","article-title":"Urinary DKK3 as a biomarker for short-term kidney function decline in children with chronic kidney disease: an observational cohort study","volume":"7","author":"Speer","year":"2023","journal-title":"Lancet Child Adolesc Health"},{"key":"2026081810415773900_bib32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.ekir.2024.09.023","article-title":"Urinary Dickkopf-3 reflects disease severity and predicts short-term kidney function decline in renal ciliopathies","volume":"10","author":"Dahmer-Heath","year":"2025","journal-title":"Kidney Int Rep"},{"key":"2026081810415773900_bib33","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1007\/s00467-025-06696-3","article-title":"Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome","volume":"40","author":"Boeckhaus","year":"2025","journal-title":"Pediatr Nephrol"},{"key":"2026081810415773900_bib34","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.ekir.2025.02.003","article-title":"Urinary Dickkopf-related protein 3\u2014a potential long-term biomarker for progressive CKD in children","volume":"10","author":"Dittrich","year":"2025","journal-title":"Kidney Int Rep"},{"key":"2026081810415773900_bib35","doi-asserted-by":"publisher","first-page":"106348","DOI":"10.1016\/j.ekir.2026.106348","article-title":"Kidney injury urine biomarker normal ranges in children","volume":"11","author":"Weber","year":"2026","journal-title":"Kidney Int Rep"},{"key":"2026081810415773900_bib36","doi-asserted-by":"publisher","first-page":"885018","DOI":"10.3389\/fmed.2022.885018","article-title":"Dickkopf 3\u2014a new indicator for the deterioration of allograft function after kidney transplantation","volume":"9","author":"Schuster","year":"2022","journal-title":"Front Med"},{"key":"2026081810415773900_bib37","doi-asserted-by":"publisher","first-page":"7454","DOI":"10.3390\/jcm13237454","article-title":"Dickkopf 3 as a new monitoring tool for kidney function after living kidney donation","volume":"13","author":"Schuster","year":"2024","journal-title":"J Clin Med"},{"key":"2026081810415773900_bib38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ajt.2024.09.016","article-title":"Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation","volume":"25","author":"de\u00a0Fallois","year":"2025","journal-title":"Am J Transplant"},{"key":"2026081810415773900_bib39","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.kint.2021.06.029","article-title":"Measurement of urinary Dickkopf-3 uncovered silent progressive kidney injury in patients with chronic obstructive pulmonary disease","volume":"100","author":"Schunk","year":"2021","journal-title":"Kidney Int"},{"key":"2026081810415773900_bib40","doi-asserted-by":"publisher","first-page":"e036637","DOI":"10.1161\/JAHA.124.036637","article-title":"Urinary Dickkopf-3 as a potential marker for estimated glomerular filtration rate decline in patients with heart failure","volume":"13","author":"Pieper","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"2026081810415773900_bib41","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1016\/j.ekir.2025.07.007","article-title":"Urinary Dickkopf-3 predicts GFR loss in the general population","volume":"10","author":"Norvik","year":"2025","journal-title":"Kidney Int Rep"},{"key":"2026081810415773900_bib42","doi-asserted-by":"publisher","first-page":"144","DOI":"10.2337\/db25-0235","article-title":"Dickkopf-3 (DKK3) and the progression of diabetic kidney disease in primary health care","volume":"75","author":"Keller","year":"2026","journal-title":"Diabetes"},{"key":"2026081810415773900_bib43","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/S0140-6736(19)30769-X","article-title":"Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study","volume":"394","author":"Schunk","year":"2019","journal-title":"Lancet"},{"key":"2026081810415773900_bib44","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1016\/j.jacc.2021.03.330","article-title":"Urinary dickkopf-3 and contrast-associated kidney damage","volume":"77","author":"Roscigno","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026081810415773900_bib45","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1093\/ndt\/gfab235","article-title":"Renal markers for monitoring acute kidney injury transition to chronic kidney disease after COVID-19","volume":"36","author":"Husain-Syed","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2026081810415773900_bib46","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1038\/s41390-022-02269-4","article-title":"Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children","volume":"93","author":"Hu","year":"2023","journal-title":"Pediatr Res"},{"key":"2026081810415773900_bib47","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3390\/biom13050752","article-title":"Update on diabetic kidney disease (DKD): focus on non-albuminuric DKD and cardiovascular risk","volume":"13","author":"Scilletta","year":"2023","journal-title":"Biomolecules"},{"key":"2026081810415773900_bib48","doi-asserted-by":"publisher","first-page":"871272","DOI":"10.3389\/fendo.2022.871272","article-title":"Comparison of nonalbuminuric and albuminuric diabetic kidney disease among patients with type 2 diabetes: a systematic review and meta-analysis","volume":"13","author":"Shi","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026081810415773900_bib49","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.2337\/dc08-2186","article-title":"Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (National Evaluation of the Frequency of Renal Impairment cO-existing with NIDDM [NEFRON] 11)","volume":"32","author":"Thomas","year":"2009","journal-title":"Diabetes Care"},{"key":"2026081810415773900_bib50","doi-asserted-by":"publisher","first-page":"100804","DOI":"10.1016\/j.xkme.2024.100804","article-title":"Measuring albuminuria in individuals with obesity: pitfalls of the urinary albumin-creatinine ratio","volume":"6","author":"Chagnac","year":"2024","journal-title":"Kidney Med"},{"key":"2026081810415773900_bib51","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1172\/JCI129937","article-title":"Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function","volume":"130","author":"Bedin","year":"2020","journal-title":"J Clin Invest"},{"key":"2026081810415773900_bib52","doi-asserted-by":"publisher","first-page":"663","DOI":"10.23876\/j.krcp.23.258","article-title":"To treat or not to treat: CUBN-associated persistent proteinuria","volume":"43","author":"Choi","year":"2024","journal-title":"Kidney Res Clin Pract"},{"key":"2026081810415773900_bib53","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3390\/cells13010075","article-title":"The multifaceted role of human Dickkopf-3 (DKK-3) in development, immune modulation and cancer","volume":"13","author":"Mourtada","year":"2023","journal-title":"Cells"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag166\/70496498\/gfag166.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag166\/70496498\/gfag166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:19:59Z","timestamp":1787066399000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article\/doi\/10.1093\/ndt\/gfag166\/8752641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":53,"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfag166","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"gfag166"}}