{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:27:58Z","timestamp":1782887278751,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. Methods: We studied 52 on-line-pre-dilution hemodiafiltration (on-l HDF) patients, 32 males and 20 females, with a mean age of 58.01 \u00b1 15.4 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22 mmol\/L. Residual renal function (RRF) was defined by interdialytic urine volume. Kaplan\u2013Meier curves and Cox regression models were performed to predict coronary artery disease (CAD), defined by ejection fraction &lt;50%, or diastolic dysfunction congestive heart failure (CHF) and peripheral vascular disease (PVD). Results: Kaplan\u2013Meier analyses showed that a lower or higher than 22 mmol\/L serum bicarbonate metabolic acidosis status was significantly associated with both PVD and diastolic dysfunction (log-rank = 5.07, p = 0.02 and log-rank = 5.84, p = 0.01, respectively). A similar prevalence of serum bicarbonate on CAD or CHF by low ejection fraction was not shown. The RRF was associated with PVD event and serum bicarbonate less than 22 mmol\/L (log-rank = 5.49, p = 0.01 and log-rank = 3.9, p = 0.04, respectively). Cox regression analysis revealed that serum bicarbonate and RRF were significant risk factors for PVD after adjustment for confounders. Furthermore, RRF adjusted for covariates was shown to be a significant risk factor for diastolic dysfunction. Conclusion: Low serum bicarbonate was associated with peripheral vascular disease and diastolic dysfunction in intermittent dialysis. The residual renal function may impact patients\u2019 outcomes through its relationship with metabolic acidosis status, particularly for peripheral vascular disease manifestation.<\/jats:p>","DOI":"10.3390\/diseases4040036","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T10:25:31Z","timestamp":1479205531000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Association between Low Serum Bicarbonate Concentrations and Cardiovascular Disease in Patients in the End-Stage of Renal Disease"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4290-8426","authenticated-orcid":false,"given":"Vaia","family":"Raikou","sequence":"first","affiliation":[{"name":"1st Department of Medicine\u2014Propaedaetic, School of Medicine, National &amp; Kapodistrian University of Athens, Athens 11527, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Kyriaki","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, General Hospital \u201cLA\u03aaKO\u201d, Athens 11527, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/01.mnh.0000203186.11772.21","article-title":"Cardiovascular disease in the dialysis population: Prognostic significance of arterial disorders","volume":"15","author":"Pannier","year":"2006","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/S0140-6736(08)60952-6","article-title":"All-cause mortality attributable to chronic kidney disease: A prospective cohort study based on 462,293 adults in Taiwan","volume":"28","author":"Wen","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1046\/j.1523-1755.1999.00422.x","article-title":"Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure","volume":"55","author":"Stenvinkel","year":"1999","journal-title":"Kidney Int."},{"key":"ref_4","first-page":"679","article-title":"Vascular calcification\u2014Pathological mechanism and clinical application\u2014. The significance of arterial calcification in unstable plaques","volume":"25","author":"Inaba","year":"2015","journal-title":"Clin. Calcium"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.0894-0959.2004.17606.x","article-title":"Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure","volume":"17","author":"Mehrotra","year":"2004","journal-title":"Semin. Dial."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1053\/j.ajkd.2015.04.014","article-title":"Predialysis and postdialysis pH and bicarbonate and risk of all-cause and cardiovascular mortality in long-term hemodialysis patients","volume":"66","author":"Yamamoto","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1525-139X.2010.00749.x","article-title":"What should define optimal correction of metabolic acidosis in chronic kidney disease?","volume":"23","author":"Chiu","year":"2010","journal-title":"Semin. Dial."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1053\/j.ajkd.2004.11.014","article-title":"Dialyzer membrane permeability and survival in hemodialysis patients","volume":"45","author":"Chauveau","year":"2005","journal-title":"Am. J. Kidney Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1681\/ASN.V451205","article-title":"Second generation logarithmic estimates of single-pool variable volume Kt\/V: An analysis of error","volume":"4","author":"Daugirdas","year":"1993","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0272-6386(00)70041-2","article-title":"Spurious metabolic acidosis in hemodialysis patients","volume":"35","author":"Kirschbaum","year":"2000","journal-title":"Am. J. Kidney Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1073-4449(12)80028-8","article-title":"Simplified equations for monitoring Kt\/V, PCRn, eKt\/V, and ePCRn","volume":"2","author":"Daugirdas","year":"1995","journal-title":"Adv. Ren. Replace Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000013385","article-title":"Plasma concentration of brain natriuretic peptide as an indicator of cardiac ventricular function in patients on hemodialysis","volume":"18","author":"Nitta","year":"1998","journal-title":"Am. J. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"F262","DOI":"10.1152\/ajprenal.00099.2005","article-title":"Dyslipidemia of chronic renal failure: The nature, mechanisms and potential consequences","volume":"290","author":"Vaziri","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.semnephrol.2004.06.026","article-title":"Oxidative stress in chronic renal failure: The nature, mechanism and consequences","volume":"24","author":"Vaziri","year":"2004","journal-title":"Semin. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1053\/ajkd.2001.20764","article-title":"Molecular mechanisms regulating protein turnover in muscle","volume":"37","author":"Price","year":"2001","journal-title":"Am. J. Kidney Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1038\/ki.1997.233","article-title":"Atherosclerosis and arteriosclerosis in chronic renal failure","volume":"51","author":"London","year":"1997","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2215\/CJN.05780612","article-title":"Dialysis modality and correction of uremic metabolic acidosis: Relationship with all-cause and cause-specific mortality","volume":"8","author":"Vashistha","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.jacc.2006.10.061","article-title":"Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: The cardiovascular health study","volume":"49","author":"Maurer","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1001\/jama.292.4.453","article-title":"Functional decline in peripheral arterial disease: Associations with the ankle brachial index and leg symptoms","volume":"292","author":"McDermott","year":"2004","journal-title":"J. Am. Med. Assoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1046\/j.1523-1755.2003.08802.x","article-title":"Metabolic acidosis in maintenance dialysis patients: Clinical considerations","volume":"88","author":"Mehrotra","year":"2003","journal-title":"Kidney Int. Suppl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0272-6386(04)00936-9","article-title":"Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"44","author":"Bommer","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2215\/CJN.00010505","article-title":"Association between serum bicarbonate and death in hemodialysis patients: Is it better to be acidotic or alkalotic?","volume":"1","author":"Wu","year":"2006","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000070205","article-title":"Metabolic acidosis of chronically hemodialyzed patients","volume":"23","author":"Kovacic","year":"2003","journal-title":"Am. J. Nephrol."},{"key":"ref_24","first-page":"139","article-title":"Vascular calcification and metabolic acidosis in end stage renal disease","volume":"13","author":"Yonova","year":"2009","journal-title":"Hippokratia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1053\/j.ackd.2008.07.011","article-title":"Vascular calcification in uremia: What is new and where are we going?","volume":"15","year":"2008","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(01)00798-3","article-title":"Parathyroid hormone-dependent signaling pathways regulating genes in bone cells","volume":"282","author":"Swarthout","year":"2002","journal-title":"Gene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s003920070103","article-title":"Mechanism of atherosclerotic calcification","volume":"89","author":"Shioi","year":"2000","journal-title":"Z. Kardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1161\/01.RES.0000249379.55535.21","article-title":"Vascular calcification: Pathobiological mechanisms and clinical implications","volume":"99","author":"Johnson","year":"2006","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1053\/j.ajkd.2015.03.032","article-title":"Serum bicarbonate and kidney disease progression and cardiovascular outcome in patients with diabetic nephropathy: A post hoc analysis of the renaal (reduction of end points in non-insulin-dependent diabetes with the angiotensin II antagonist losartan) study and IDNT (Irbesartan diabetic nephropathy trial)","volume":"66","author":"Schutte","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1053\/j.ajkd.2013.01.017","article-title":"Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: A report from the Chronic Renal Insufficiency Cohort (CRIC) study","volume":"62","author":"Dobre","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_31","first-page":"539","article-title":"Oral treatment of metabolic acidosis in hemodialyzed patients and the implications on the hemodynamic status","volume":"54","author":"Checherita","year":"2013","journal-title":"Rom. J. Morphol. Emplryol."},{"key":"ref_32","first-page":"63","article-title":"The pathophysiology of heart failure with preserved ejection fraction and its therapeutic implications","volume":"28","year":"2009","journal-title":"Rev. Port. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.kint.2016.02.037","article-title":"Preservation of residual kidney function in hemodialysis patients: Reviving an old concept","volume":"90","author":"Mathew","year":"2016","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marr\u00f3n, B., Rem\u00f3n, C., P\u00e9rez-Font\u00e1n, M., Quir\u00f3s, P., and Ort\u00edz, A. (2008). Benefits of preserving residual renal function in peritoneal dialysis. Kidney Int. Suppl., S42\u2013S51.","DOI":"10.1038\/sj.ki.5002600"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chang, T.I., Oh, H.J., Kang, E.W., Yoo, T.H., Shin, S.K., Kang, S.W., Choi, K.H., Han, D.S., and Han, S.H. (2013). A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082912"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/4\/4\/36\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:35:35Z","timestamp":1760211335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/4\/4\/36"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,15]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["diseases4040036"],"URL":"https:\/\/doi.org\/10.3390\/diseases4040036","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,15]]}}}