{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:34:04Z","timestamp":1777678444588,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45\u201366) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4\u201382.7) \u00b5g\/mL and 47 (IQ 13\u2013119) mL\/min\/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.<\/jats:p>","DOI":"10.3390\/life11030210","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T12:12:18Z","timestamp":1615205538000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Ana","family":"Cerqueira","sequence":"first","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), Nephrology and Infectious Diseases Research Group, University of Porto, 4200-250 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-1848","authenticated-orcid":false,"given":"Janete","family":"Quelhas-Santos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), Nephrology and Infectious Diseases Research Group, University of Porto, 4200-250 Porto, Portugal"}]},{"given":"In\u00eas","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), Nephrology and Infectious Diseases Research Group, University of Porto, 4200-250 Porto, Portugal"}]},{"given":"Susana","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), Nephrology and Infectious Diseases Research Group, University of Porto, 4200-250 Porto, Portugal"}]},{"given":"Miguel","family":"Relvas","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"N\u00eddia","family":"Marques","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9356-3272","authenticated-orcid":false,"given":"Cl\u00e1udia Camila","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Community Medicine Health Information and Decision, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"CINTESIS\u2013Center for Health Technology and Services Research, 4200-250 Porto, Portugal"}]},{"given":"Manuel","family":"Pestana","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal"},{"name":"Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), Nephrology and Infectious Diseases Research Group, University of Porto, 4200-250 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMp058318","article-title":"Chronic kidney disease in the developing world","volume":"354","author":"Barsoum","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"c269","DOI":"10.1159\/000321382","article-title":"The burden of Chronic Kidney Disease on developing nations: A 21st century challenge in global health","volume":"118","author":"Nugent","year":"2011","journal-title":"Nephron Clin. Pract."},{"key":"ref_3","first-page":"1121","article-title":"Level of kidney function as a risk factor for cardiovascular outcomes in the elderly","volume":"63","author":"Manjunath","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1111\/j.1523-1755.2004.09203.x","article-title":"Cardiovascular risk in chronic kidney disease","volume":"66","author":"Anavekar","year":"2004","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1161\/01.CIR.0000095676.90936.80","article-title":"Wilson Kidney Disease as a Risk Factor for Development of Cardiovascular Disease","volume":"108","author":"Sarnak","year":"2003","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/sj.ki.5000284","article-title":"The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population","volume":"69","author":"Irie","year":"2006","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.2215\/CJN.11291210","article-title":"Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients","volume":"6","author":"Tripepi","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0140-6736(13)60595-4","article-title":"Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention","volume":"382","author":"Gansevoort","year":"2013","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/ejhf.799","article-title":"Neprilysin inhibition in heart failure: Mechanisms and substrates beyond modulating natriuretic peptides","volume":"19","author":"Iacovoni","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehr253","article-title":"Therapeutic perspectives in hypertension: Novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches","volume":"32","author":"Unger","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1172\/JCI24066","article-title":"Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure","volume":"115","author":"Xu","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/mp.2009.74","article-title":"Renalase, a novel soluble FAD-dependent protein, is synthesized in the brain and peripheral nerves","volume":"15","author":"Hennebry","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jash.2015.08.002","article-title":"Circulating renalase, catecholamines, and vascular adhesion protein 1 in hypertensive patients","volume":"9","author":"Maciorkowska","year":"2015","journal-title":"J. Am. Soc. Hypertens."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s10157-014-0951-8","article-title":"Serum renalase is related to catecholamine levels and renal function","volume":"19","author":"Wang","year":"2015","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.5603\/KP.a2018.0108","article-title":"Renalase is associated with adverse left atrial remodelling and disease burden in patients with atrial fibrillation undergoing pulmonary vein isolation","volume":"76","author":"Wybraniec","year":"2018","journal-title":"Kardiol. Pol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, I.-T., and Sheu, W.H.-H. (2018). Serum Renalase Levels Are Predicted by Brain-Derived Neurotrophic Factor and Associated with Cardiovascular Events and Mortality after Percutaneous Coronary Intervention. J. Clin. Med., 7.","DOI":"10.3390\/jcm7110437"},{"key":"ref_18","unstructured":"Baek, S.H., Cha, R.H., Kang, S.W., Park, C.W., Cha, D.R., Kim, S.G., Yoon, S.A., Kim, S., Han, S.Y., and Park, J.H. (2017). Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease. Korean J. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1016\/j.transproceed.2011.08.032","article-title":"Renalase, a novel regulator of blood pressure, is predicted by kidney function in renal transplant recipients","volume":"43","author":"Malyszko","year":"2011","journal-title":"Transplant. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1177\/1535370214522182","article-title":"Plasma and urine renalase levels and activity during the recovery of renal function in kidney transplant recipients","volume":"239","author":"Ferreira","year":"2014","journal-title":"Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3747\/pdi.2011.00118","article-title":"Renalase in peritoneal dialysis patients is not related to blood pressure, but to dialysis vintage","volume":"32","author":"Zbroch","year":"2012","journal-title":"Perit. Dial. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1159\/000338178","article-title":"Renalase, a Novel Enzyme Involved in Blood Pressure Regulation, Is Related to Kidney Function but Not to Blood Pressure in Hemodialysis Patients","volume":"35","author":"Zbroch","year":"2012","journal-title":"Kidney Blood Press. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1476-511X-13-135","article-title":"Markers of increased cardiovascular risk in patients with chronic kidney disease","volume":"13","author":"Nocun","year":"2014","journal-title":"Lipids Health Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1080\/1354750X.2019.1642957","article-title":"Renalase in children with chronic kidney disease","volume":"24","author":"Skrzypczyk","year":"2019","journal-title":"Biomarkers"},{"key":"ref_25","first-page":"790","article-title":"Chronic kidney disease is associated with increased levels of renalase in serum and decreased in erythrocytes","volume":"129","author":"Wisniewska","year":"2019","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Serwin, N.M., Wisniewska, M., Cecerska-Heryc, E., Safranow, K., Skwirczynska, E., and Dolegowska, B. (2020). Serum-to-urine renalase ratio and renalase fractional excretion in healthy adults and chronic kidney disease patients. BMC Nephrol., 21.","DOI":"10.1186\/s12882-020-01737-5"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3109\/0886022X.2012.681534","article-title":"Renalase, stroke, and hypertension in hemodialyzed patients","volume":"34","author":"Malyszko","year":"2012","journal-title":"Ren. Fail."},{"key":"ref_28","first-page":"1048","article-title":"Vascular adhesion protein-1 and renalase in regard to diabetes in hemodialysis patients","volume":"8","author":"Malyszko","year":"2012","journal-title":"Arch. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3109\/0886022X.2013.778754","article-title":"Circulating levels of renalase, norepinephrine, and dopamine in dialysis patients","volume":"35","author":"Zbroch","year":"2013","journal-title":"Ren. Fail."},{"key":"ref_30","first-page":"132","article-title":"Relationship between renalase and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) in haemodialysis patients","volume":"21","author":"Dziedzic","year":"2014","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1080\/0886022X.2016.1208516","article-title":"Increased serum renalase in hemodialysis patients: Is it related to left ventricular hypertrophy?","volume":"38","author":"Oguz","year":"2016","journal-title":"Ren. Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.nefro.2016.11.013","article-title":"Increased serum renalase in peritoneal dialysis patients: Is it related to cardiovascular disease risk?","volume":"37","author":"Akoglu","year":"2017","journal-title":"Nefrologia"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wisniewska, M., Serwin, N., Dziedziejko, V., Marchelek-Mysliwiec, M., Dolegowska, B., Domanski, L., Ciechanowski, K., Safranow, K., and Pawlik, A. (2021). Renalase in Haemodialysis Patients with Chronic Kidney Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040680"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.20452\/pamw.1132","article-title":"Renalase, kidney function, and markers of endothelial dysfunction in renal transplant recipients","volume":"122","author":"Zbroch","year":"2012","journal-title":"Pol. Arch. Med. Wewn"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12659\/AOT.892632","article-title":"The assessment of renalase: Searching for the best predictor of early renal dysfunction by multivariate modeling in stable renal transplant recipients","volume":"20","author":"Stojanovic","year":"2015","journal-title":"Ann. Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/1526924817699956","article-title":"Renalase Assessment With Regard to Kidney Function, Lipid Disturbances, and Endothelial Dysfunction Parameters in Stable Renal Transplant Recipients","volume":"27","author":"Stojanovic","year":"2017","journal-title":"Prog. Transplant."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/3\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:44Z","timestamp":1760160884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/3\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["life11030210"],"URL":"https:\/\/doi.org\/10.3390\/life11030210","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]}}}