{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:44:46Z","timestamp":1784090686635,"version":"3.55.0"},"reference-count":43,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Herlev and Gentofte Hospital","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF19OC0058900"],"award-info":[{"award-number":["NNF19OC0058900"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,5,14]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetic kidney disease is a severe complication of diabetes. The diagnosis is based on clinical characteristics such as persistently elevated albuminuria, hypertension and decline in kidney function, although this definition is not specific to kidney disease caused by diabetes. The only way to establish an accurate diagnosis\u2014diabetic nephropathy\u2014is by performing a kidney biopsy. The histological presentation of diabetic nephropathy can be associated with a heterogeneous range of histological features with many pathophysiological factors involved demonstrating the complexity of the condition. Current treatment strategies aim to slow disease progression and are not specific to the underlying pathological processes.<\/jats:p>\n                    <jats:p>This study will investigate the prevalence of diabetic nephropathy in individuals with type 2 diabetes (T2D) and severely elevated albuminuria. The deep molecular characterisation of the kidney biopsy and biological specimens may pave the way for improved diagnostic accuracy and a better understanding of the pathological processes involved and may also reveal new targets for individualised treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      In the PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy 2 study, research kidney biopsies will be performed in 300 participants with T2D, urine albumin\/creatinine ratio \u2265700\u2009mg\/g and estimated glomerular filtration ratio &gt;30\u2009mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      . Cutting-edge molecular technologies will be applied to the kidney, blood, urine, faeces and saliva samples for comprehensive multi-omics profiling. The associated disease course and clinical outcomes will be assessed by annual follow-up for 20 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The Danish Regional Committee on Health Research Ethics and the Knowledge Center on Data Protection (in the Capital Region of Denmark) have granted approval for the study. The results will be published in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04916132\">NCT04916132<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072216","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T03:56:24Z","timestamp":1686110184000},"page":"e072216","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Rationale and design of a prospective, clinical study of kidney biopsies in people with type 2 diabetes and severely increased albuminuria (the PRIMETIME 2 study)"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04916132","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1248-1740","authenticated-orcid":false,"given":"Marie","family":"M\u00f8ller","sequence":"first","affiliation":[{"name":"Department of Nephrology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"Borg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Zealand University Hospital, Roskilde, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Bressendorff","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth N","family":"Fink","sequence":"additional","affiliation":[{"name":"Gubra ApS, H\u00f8rsholm, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Gravesen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Haar","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Zealand University Hospital, Roskilde, Denmark"},{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Hansen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorrit","family":"Krustrup","sequence":"additional","affiliation":[{"name":"Department of Pathology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-6638","authenticated-orcid":false,"given":"Frederik","family":"Persson","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederikke E","family":"Sembach","sequence":"additional","affiliation":[{"name":"Gubra ApS, H\u00f8rsholm, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C B","family":"Thuesen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Copenhagen University Hospital \u2013 Herlev and Gentofte, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"2025121410580971000_13.6.e072216.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"2025121410580971000_13.6.e072216.2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116"},{"key":"2025121410580971000_13.6.e072216.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"2025121410580971000_13.6.e072216.4","unstructured":"Chertow G , Luyckx V , Marsden P , et al . Brenner and Rector\u2019s the kidney. In: Diabetic Nephropathy. Elsevier, 2019: 39."},{"key":"2025121410580971000_13.6.e072216.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2017.10.003"},{"key":"2025121410580971000_13.6.e072216.6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4239\/wjd.v4.i6.245","article-title":"Diabetic nephropathy: is it time yet for routine kidney biopsy","volume":"4","author":"Gonzalez Suarez","year":"2013","journal-title":"World J Diabetes"},{"key":"2025121410580971000_13.6.e072216.7","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/nrdp.2015.18","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"2025121410580971000_13.6.e072216.8","unstructured":"Haar K , Rossing P , Persson F , et al . Design and methodology of The PRIMETIME 1 cohort study, PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy. To be Submitt,"},{"key":"2025121410580971000_13.6.e072216.9","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"2025121410580971000_13.6.e072216.10","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010010010"},{"key":"2025121410580971000_13.6.e072216.11","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2147\/CLEP.S99507","article-title":"The Danishregistry of diabetic retinopathy","volume":"8","author":"Andersen","year":"2016","journal-title":"Clin Epidemiol"},{"key":"2025121410580971000_13.6.e072216.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2004.12.009"},{"key":"2025121410580971000_13.6.e072216.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2022-003058","article-title":"Prevalence of non-diabetic kidney disease and inability of clinical predictors to differentiate it from diabetic kidney disease: results from a prospectively performed renal biopsy study","volume":"10","author":"Basu","year":"2022","journal-title":"BMJ Open Diab Res Care"},{"key":"2025121410580971000_13.6.e072216.14","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.13061019"},{"key":"2025121410580971000_13.6.e072216.15","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02510213"},{"key":"2025121410580971000_13.6.e072216.16","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw070"},{"key":"2025121410580971000_13.6.e072216.17","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s13300-020-00888-w","article-title":"Insights into the role of renal biopsy in patients with T2Dm: A literature review of global renal biopsy results","volume":"11","author":"Tong","year":"2020","journal-title":"Diabetes Ther"},{"key":"2025121410580971000_13.6.e072216.18","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2017-000412","article-title":"Presentation, pathology and prognosis of renal disease in type 2 diabetes","volume":"5","author":"Tan","year":"2017","journal-title":"BMJ Open Diabetes Res Care"},{"key":"2025121410580971000_13.6.e072216.19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0064184","article-title":"Identifying parameters to distinguish non-diabetic renal diseases from diabetic nephropathy in patients with type 2 diabetes mellitus: A meta-analysis","volume":"8","author":"Liang","year":"2013","journal-title":"PLoS One"},{"key":"2025121410580971000_13.6.e072216.20","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021010017"},{"key":"2025121410580971000_13.6.e072216.21","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0204"},{"key":"2025121410580971000_13.6.e072216.22","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07420619"},{"key":"2025121410580971000_13.6.e072216.23","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020071082"},{"key":"2025121410580971000_13.6.e072216.24","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/s41591-019-0415-5","article-title":"A signature of circulating inflammatory proteins and development of end stage renal disease in diabetes","volume":"25","author":"Niewczas","year":"2019","journal-title":"Nat Med"},{"key":"2025121410580971000_13.6.e072216.25","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016101101"},{"key":"2025121410580971000_13.6.e072216.26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310345"},{"key":"2025121410580971000_13.6.e072216.27","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2013.10.048"},{"key":"2025121410580971000_13.6.e072216.28","unstructured":"Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease . Towar Precis MED build a Knowl NETW Biomed Res a new Taxon DIS. 2011: 1\u2013128. Available: https:\/\/pubmed.ncbi.nlm.nih.gov\/22536618\/"},{"key":"2025121410580971000_13.6.e072216.29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4093\/dmj.2020.0217","article-title":"Treatment of diabetic kidney disease: current and future","volume":"45","author":"Yamazaki","year":"2021","journal-title":"Diabetes Metab J"},{"key":"2025121410580971000_13.6.e072216.30","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.02.330"},{"key":"2025121410580971000_13.6.e072216.31","doi-asserted-by":"crossref","unstructured":"Examination of the end-stage kidney. Diagnostic Pathol Kidney Dis 2016:1040\u20135.","DOI":"10.1016\/B978-0-323-37707-2.50255-X"},{"key":"2025121410580971000_13.6.e072216.32","doi-asserted-by":"crossref","unstructured":"Gluck C , Ko YA , Susztak K . Precision medicine approaches to diabetic kidney disease. Curr Diab Rep 2017;17. doi:10.1007\/s11892-017-0854-7","DOI":"10.1007\/s11892-017-0854-7"},{"key":"2025121410580971000_13.6.e072216.33","unstructured":"Andrulli S , Rossini M , Gigliotti G , et al . The risks associated with percutaneous native kidney biopsies: a prospective study. Nephrol Dial Transplant May 19, 2022. Available: https:\/\/academic-oup-com.ep.fjernadgang.kb.dk\/ndt\/advance-article\/doi\/10.1093\/ndt\/gfac177\/6589424"},{"key":"2025121410580971000_13.6.e072216.34","first-page":"1591","article-title":"Safety and complications of percutaneous kidney biopsies in 715 children and 8573 adults in Norway 1988-2010","volume":"7","author":"T\u00f8ndel","year":"2012","journal-title":"Clin J"},{"key":"2025121410580971000_13.6.e072216.35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-0039-1688422","article-title":"Complications of percutaneous renal biopsy","volume":"36","author":"Bakdash","year":"2019","journal-title":"Semin Intervent Radiol"},{"key":"2025121410580971000_13.6.e072216.36","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ekir.2021.11.013","article-title":"Association between diabetes and major bleeding complications of renal biopsy","volume":"7","author":"Hasegawa","year":"2022","journal-title":"Kidney International Reports"},{"key":"2025121410580971000_13.6.e072216.37","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.2215\/CJN.14721219","article-title":"Major bleeding and risk of death after percutaneous native kidney biopsies a French nationwide cohort study","volume":"15","author":"Halimi","year":"2020","journal-title":"CJASN"},{"key":"2025121410580971000_13.6.e072216.38","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41581-021-00462-y","article-title":"Trajectories of kidney function in diabetes: a Clinicopathological update","volume":"17","author":"Oshima","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2025121410580971000_13.6.e072216.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.01.023"},{"key":"2025121410580971000_13.6.e072216.40","unstructured":"Indvandrere og efterkommere . Danmarks Statistik. n.d. Available: https:\/\/www.dst.dk\/da\/Statistik\/emner\/borgere\/befolkning\/indvandrere-og-efterkommere"},{"key":"2025121410580971000_13.6.e072216.41","unstructured":"Welcome to the kidney precision medicine project. 2022. Available: https:\/\/www.kpmp.org\/"},{"key":"2025121410580971000_13.6.e072216.42","first-page":"S14","article-title":"Classification and diagnosis of diabetes: standards of medical care in Diabetes-2020","volume":"43(Supplement_1)","year":"2020","journal-title":"Diabetes Care"},{"key":"2025121410580971000_13.6.e072216.43","unstructured":"Kellum JA , Aspelin P , Karolinska UH , et al . KDIGO Clinical Practice Guideline for Acute Kidney Injury. 2012."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-072216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T18:58:20Z","timestamp":1765738700000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-072216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,6]]},"published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1136\/bmjopen-2023-072216"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-072216","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]}}}