{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T22:35:07Z","timestamp":1773354907801,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"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>Background: Patients with chronic kidney disease (CKD) have markedly increased rates of end stage renal disease, major adverse cardiovascular\/cerebrovascular events (MACCEs), and mortality. Endothelial dysfunction (ED) is an early marker of atherosclerosis that is emerging as an increasingly important non-traditional cardiovascular risk factor in CKD. There is a lack of clinical studies examining the association between ED and both cardiovascular and renal endpoints in patients with CKD. Aims: We examined the association between reactive hyperemia index (RHI), a validated measure of endothelial function measured by peripheral arterial tonometry (PAT), with traditional cardiovascular risk factors in pre-dialysis CKD patients and prospectively evaluated the role of RHI as predictor of renal and cardiovascular outcomes in this population. Methods: One hundred and twenty pre-dialysis patients with CKD stages 1 to 5 (CKD group) and 18 healthy kidney donor candidates (control group) were recruited and had a successful RHI measurement by PAT. General demographic and clinical information including traditional cardiovascular risk factors were registered from all participants. Thereafter, patients were prospectively followed-up for a median time of 47 (IQR 19\u201366) months to determine associations of RHI with renal outcomes, MACCEs, hospitalizations or mortality. Results: In the CKD patient population, the mean age was 57.7 \u00b1 15.5 years, the mean eGFR was 54.9 \u00b1 36.7 mL\/min\/1.73 m2 (CKD-EPI) and 57 were males (47.5%). At baseline, in univariate analysis, RHI in the CKD group correlated positively with eGFR (r = 0.332, p &lt; 0.0001) and correlated negatively with age (r = \u22120.469, p &lt; 0.0001), Charlson index (r = \u22120.399, p &lt; 0.0001), systolic blood pressure (r = \u22120.256, p = 0.005), and proteinuria (r = 0.211, p = 0.027). Reactive hyperemia index in the control group did not significantly differ from RHI observed in patients with CKD stages 1 to 5 (2.09 \u00b1 0.40 vs. 2.01 \u00b1 0.06, p = 0.493). In adjusted analysis, only age (\u03b2 = \u22120.014, p = 0.003) remained independently associated with RHI at baseline. During follow-up, 8 patients suffered a MACCEs, 33 patients experienced renal function deterioration, 17 patients were hospitalized for medical reasons and 6 patients died. RHI at baseline was not significantly associated with CKD progression (1.94 vs. 2.02, p = 0.584), hospitalizations (1.90 vs. 2.04, p = 0.334), and all-cause mortality (1.65 vs. 2.01, p = 0.208) or MACCEs (1.77 vs. 2.01, p = 0.356), but was significantly associated with cerebrovascular events (1.27 vs. 2.02, p = 0.004) and with a composite cardiovascular outcome (MACCEs, hospital admissions and death; 1.73 vs. 2.07, p = 0.035). Conclusion: Our results suggest that RHI may be a predictor for the development of cerebrovascular events in pre-dialysis CKD patients who may benefit from more aggressive preventive measures.<\/jats:p>","DOI":"10.3390\/life11020128","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T23:38:44Z","timestamp":1613173124000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Endothelial Dysfunction Is Associated with Cerebrovascular Events in Pre-Dialysis CKD Patients: A Prospective Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-0883","authenticated-orcid":false,"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":"Faculty of Medicine, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-3740","authenticated-orcid":false,"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":"Miguel","family":"Relvas","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5520-6899","authenticated-orcid":false,"given":"N\u00eddia","family":"Marques","sequence":"additional","affiliation":[{"name":"Nephrology Department, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-2024","authenticated-orcid":false,"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":[[2021,2,7]]},"reference":[{"key":"ref_1","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. 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