{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:12:16Z","timestamp":1793056336580,"version":"4.5.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2023,1]]},"abstract":"\n Significance Statement<\/jats:title>\n Standard blood markers of kidney function undergo renal clearance and are thus inversely correlated with estimated glomerular filtration rate (eGFR). Recent work has shown that blood levels of the podocyte-derived protein testican-2 are positively correlated with eGFR among individuals with relatively normal kidney function. The current study considers blood testican-2 levels among three cohorts of >8,000 individuals in total, including many with established kidney disease. Testican-2 levels are positively correlated with eGFR across the full range of kidney health, with higher levels associated with lower risk of incident end stage kidney disease (ESKD), even after adjusting for baseline eGFR, proteinuria, and other kidney disease risk factors. This study highlights a positive association between testican-2 and kidney health and prognosis.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with eGFR and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of ESKD is unknown.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK,\n n<\/jats:italic>\n =703), the Chronic Renal Insufficiency Cohort (CRIC) study (\n n<\/jats:italic>\n =3196), and the Atherosclerosis Risk in Communities (ARIC) study (\n n<\/jats:italic>\n =4378). We compared baseline characteristics by testican-2 tertile and used Cox proportional hazards models to study the association of testican-2 with incident ESKD.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Higher testican-2 levels were associated with higher measured GFR (mGFR) in AASK, higher eGFR in the CRIC and ARIC studies, and lower albuminuria in all cohorts. Baseline testican-2 levels were significantly associated with incident ESKD in Cox proportional hazards models adjusted for age, sex, and race (model 1) and model 1+mGFR or eGFR+comorbidities (model 2). In model 3 (model 2+proteinuria), the associations between testican-2 (per SD increase) and incident ESKD were AASK (hazard ratio [HR]=0.84 [0.72 to 0.98],\n P<\/jats:italic>\n =0.023), CRIC (HR=0.95 [0.89 to 1.02],\n P<\/jats:italic>\n =0.14), ARIC (HR=0.54 [0.36 to 0.83],\n P<\/jats:italic>\n =0.0044), and meta-analysis (HR=0.92 [0.86 to 0.98],\n P<\/jats:italic>\n =0.0073).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Across three cohorts spanning >8000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2022020216","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T16:05:13Z","timestamp":1666800313000},"page":"122-131","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Testican-2 Is Associated with Reduced Risk of Incident ESKD"],"prefix":"10.1681","volume":"34","author":[{"given":"Donghai","family":"Wen","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Surapaneni","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron C.","family":"Hoogeveen","sequence":"additional","affiliation":[{"name":"Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System"},{"name":"University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrut S.","family":"Waikar","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"Sections of Preventive Medicine and Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"},{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Kimmel","sequence":"additional","affiliation":[{"name":"Division of Kidney Urologic and Hematologic Diseases, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth F.","family":"Dubin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat","family":"Deo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold I.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ganz","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Grams","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"},{"name":"Department of Medicine, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene P.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the CKD 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