{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:11:01Z","timestamp":1781359861682,"version":"3.54.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The combination of chronic kidney disease (CKD), chronic heart failure (HF), and anaemia, the so-called cardio-renal-anaemia syndrome (CRA) is associated with dysregulation of erythropoietin levels and inflammation. Both have been associated with the development of cancer. This study aimed to determine the cumulative incidence of cancer in patients with CRA, as compared with anaemic CKD and control patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Patients aged &amp;lt;80 years who attended the nephrology or cardiology outpatient clinics between March 2006 and November 2007 were eligible for inclusion in this retrospective case\u2013control study if haemoglobin &amp;lt;8.1 mmol\/L (13 g\/dL) and serum creatinine &amp;gt;80 mmol\/L (0.90 mg\/dL). Medical records dating back to 1996 were reviewed. The relationship between cancer and CRA, chronic HF, CKD, and anaemia was analysed using logistic regression analysis. Data from 1087 patients were reviewed. We identified 348 patients with both CKD and anaemia, of whom 132(38.3%) had CRA. The control group included 264 patients attending the hypertension outpatient clinic. Patients with CRA had a 19% cumulative incidence of cancer compared with 11% for patients with anaemia, CKD and no chronic HF, and 11% in the control group. The odds ratio (OR) for cancer was 1.8(95% CI 1.0\u20133.2) for the CRA group compared with the control group. Chronic HF was an independent risk factor for cancer after correction for age and gender (adjusted OR 2.0; 95% CI 1.2\u20133.3, P = 0.007).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The cumulative incidence of cancer among patients with CRA is high compared with controls and to anaemic CKD patients without chronic HF. Chronic HF was an independent risk factor for cancer. These results stress the importance of clarifying the mechanisms involved in the development of cancer in CRA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfq078","type":"journal-article","created":{"date-parts":[[2010,5,22]],"date-time":"2010-05-22T20:25:57Z","timestamp":1274559957000},"page":"855-860","source":"Crossref","is-referenced-by-count":10,"title":["High Cumulative Incidence of Cancer in Patients with Cardio-Renal-Anaemia Syndrome"],"prefix":"10.1093","volume":"12","author":[{"given":"Nicolas F.","family":"Schroten","sequence":"first","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karien","family":"van der Putten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans H.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adry","family":"Diepenbroek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend","family":"Mosterd","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]},{"name":"Heart and Lung Center, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo A.J.M.","family":"Gaillard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]},{"name":"Department of Nephrology, VU University Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"2026020203351558100_ejhfhfq078-bib-0001","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/eurheartj\/ehi020","article-title":"The severe cardiorenal syndrome: \u2018Guyton revisited","volume":"26","author":"Bongartz","year":"2005","journal-title":"Eur Heart J"},{"key":"2026020203351558100_ejhfhfq078-bib-0002","doi-asserted-by":"crossref","first-page":"F932","DOI":"10.1152\/ajprenal.00200.2006","article-title":"Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors","volume":"291","author":"Jie","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026020203351558100_ejhfhfq078-bib-0003","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1158\/1078-0432.CCR-05-1771","article-title":"Erythropoietin biology in cancer","volume":"12","author":"Hardee","year":"2006","journal-title":"Clin Cancer Res"},{"key":"2026020203351558100_ejhfhfq078-bib-0004","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejheart.2007.10.008","article-title":"Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit","volume":"10","author":"Lipsic","year":"2008","journal-title":"Eur J Heart Fail"},{"key":"2026020203351558100_ejhfhfq078-bib-0005","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1111\/j.1523-1755.2004.00880.x","article-title":"Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia","volume":"66","author":"Fehr","year":"2004","journal-title":"Kidney Int"},{"key":"2026020203351558100_ejhfhfq078-bib-0006","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood.V54.4.877.877","article-title":"Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function","volume":"54","author":"Radtke","year":"1979","journal-title":"Blood"},{"key":"2026020203351558100_ejhfhfq078-bib-0007","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/eurheartj\/ehl419","article-title":"Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well","volume":"28","author":"Westenbrink","year":"2007","journal-title":"Eur Heart J"},{"key":"2026020203351558100_ejhfhfq078-bib-0008","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1159\/000148256","article-title":"Hypoxia and hypoxia-inducible factor in renal disease","volume":"110","author":"Nangaku","year":"2008","journal-title":"Nephron Exp Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0009","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1172\/JCI30117","article-title":"Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo","volume":"117","author":"Rankin","year":"2007","journal-title":"J Clin Invest"},{"key":"2026020203351558100_ejhfhfq078-bib-0010","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2169\/internalmedicine.43.649","article-title":"Molecular biology of erythropoietin","volume":"43","author":"Jelkmann","year":"2004","journal-title":"Intern Med"},{"key":"2026020203351558100_ejhfhfq078-bib-0011","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3317\/jraas.2001.040","article-title":"Losartan may modulate erythropoietin production","volume":"2","author":"Donnelly","year":"2001","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2026020203351558100_ejhfhfq078-bib-0012","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1053\/ajkd.2002.31404","article-title":"Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis","volume":"39","author":"Wang","year":"2002","journal-title":"Am J Kidney Dis"},{"key":"2026020203351558100_ejhfhfq078-bib-0013","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1046\/j.1365-2362.1999.00530.x","article-title":"Angiotensin II increases erythropoietin production in healthy human volunteers","volume":"29","author":"Freudenthaler","year":"1999","journal-title":"Eur J Clin Invest"},{"key":"2026020203351558100_ejhfhfq078-bib-0014","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ncpneph0655","article-title":"Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure","volume":"4","author":"van der Putten","year":"2008","journal-title":"Nat Clin Pract Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0015","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1016\/j.ejca.2006.07.006","article-title":"JAK\/STAT signalling pathway in colorectal cancer: a new biological target with therapeutic implications","volume":"42","author":"Spano","year":"2006","journal-title":"Eur J Cancer"},{"key":"2026020203351558100_ejhfhfq078-bib-0016","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1593\/neo.04685","article-title":"Erythropoietin signaling promotes invasiveness of human head and neck squamous cell carcinoma","volume":"7","author":"Mohyeldin","year":"2005","journal-title":"Neoplasia"},{"key":"2026020203351558100_ejhfhfq078-bib-0017","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0002-9440(10)64314-3","article-title":"Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression","volume":"162","author":"Acs","year":"2003","journal-title":"Am J Pathol"},{"key":"2026020203351558100_ejhfhfq078-bib-0018","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1634\/theoncologist.2008-0110","article-title":"Erythropoietin and its receptor in breast cancer: putting together the pieces of the puzzle","volume":"13","author":"Mannello","year":"2008","journal-title":"Oncologist"},{"key":"2026020203351558100_ejhfhfq078-bib-0019","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"2026020203351558100_ejhfhfq078-bib-0020","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1681\/ASN.2008090998","article-title":"Association of CKD and cancer risk in older people","volume":"20","author":"Wong","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0021","doi-asserted-by":"crossref","first-page":"604","DOI":"10.2215\/CJN.03931106","article-title":"Screening, diagnosis, and treatment of cancer in long-term dialysis patients","volume":"2","author":"Holley","year":"2007","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0022","first-page":"166","article-title":"Are chronic dialysis patients at increased risk for cancer?","volume":"21","author":"Mandayam","year":"2008","journal-title":"J Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0023","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S0272-6386(12)70323-2","article-title":"Evidence for increased cancer deaths in chronic dialysis patients","volume":"22","author":"Iseki","year":"1993","journal-title":"Am J Kidney Dis"},{"key":"2026020203351558100_ejhfhfq078-bib-0024","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/01.ASN.0000039608.81046.81","article-title":"Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: analysis of data from the United States, Europe, and Australia and New Zealand","volume":"14","author":"Stewart","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0025","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0272-6386(89)80187-8","article-title":"Neoplasms in dialysis patients: a population-based study","volume":"14","author":"Port","year":"1989","journal-title":"Am J Kidney Dis"},{"key":"2026020203351558100_ejhfhfq078-bib-0026","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1023\/A:1014489911153","article-title":"Increased incidence of neoplasia in chronic renal failure (20-year experience)","volume":"33","author":"Cengiz","year":"2002","journal-title":"Int Urol Nephrol"},{"key":"2026020203351558100_ejhfhfq078-bib-0027","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1161\/CIRCULATIONAHA.105.610642","article-title":"Drawbacks and prognostic value of formulas estimating renal function in patients with chronic heart failure and systolic dysfunction","volume":"114","author":"Smilde","year":"2006","journal-title":"Circulation"},{"key":"2026020203351558100_ejhfhfq078-bib-0028","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.ejheart.2008.08.005","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)","volume":"10","author":"Dickstein","year":"2008","journal-title":"Eur J Heart Fail"},{"key":"2026020203351558100_ejhfhfq078-bib-0029","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1002\/(SICI)1097-0258(19981130)17:22<2635::AID-SIM954>3.0.CO;2-C","article-title":"Improved confidence intervals for the difference between binomial proportions based on paired data","volume":"17","author":"Newcombe","year":"1998","journal-title":"Stat Med"},{"key":"2026020203351558100_ejhfhfq078-bib-0030","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1056\/NEJMoa0907845","article-title":"TREAT Investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease","volume":"361","author":"Pfeffer","year":"2009","journal-title":"N Engl J Med"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfq078","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/12\/8\/855\/66522696\/eurjhf_12_8_855.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/12\/8\/855\/66522696\/eurjhf_12_8_855.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:35:28Z","timestamp":1770021328000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/12\/8\/855\/8435927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,1]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2014,1,13]]},"published-print":{"date-parts":[[2010,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjhf\/hfq078","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,8]]},"published":{"date-parts":[[2010,8,1]]}}}