Endothelial Dysfunction Is Associated with Cerebrovascular Events in Pre-Dialysis CKD Patients: A Prospective Study

• Published in: Life (Basel, Switzerland) Switzerland), 2021-02, Vol.11 (2), p.128
• Main Authors: Cerqueira, Ana, Quelhas-Santos, Janete, Sampaio, Susana, Ferreira, Inês, Relvas, Miguel, Marques, Nídia, Dias, Cláudia Camila, Pestana, Manuel
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Age; Angina pectoris; Arteriosclerosis; Atherosclerosis; Blood pressure; Cardiovascular diseases; cardiovascular risk; cerebrovascular events; chronic kidney disease; Diabetes; Dialysis; endothelial dysfunction; Endothelium; Epidermal growth factor receptors; Health risks; Heart failure; Hemodialysis; Hyperemia; Hypertension; Kidney diseases; Kidneys; Mortality; Outpatient care facilities; Patients; peripheral arterial tonometry; Population; Proteinuria; reactive hyperemia index; Renal function; Risk analysis; Risk factors
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life11020128

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. 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. 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 19-66) months to determine associations of RHI with renal outcomes, MACCEs, hospitalizations or mortality. In the CKD patient population, the mean age was 57.7 ± 15.5 years, the mean eGFR was 54.9 ± 36.7 mL/min/1.73 m (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, < 0.0001) and correlated negatively with age (r = -0.469, < 0.0001), Charlson index (r = -0.399, < 0.0001), systolic blood pressure (r = -0.256, = 0.005), and proteinuria (r = 0.211, = 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 ± 0.40 vs. 2.01 ± 0.06, = 0.493). In adjusted analysis, only age (β = -0.014, = 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, = 0.584), hospitalizations (1.90 vs. 2.04, = 0.334), and all-cause mortality (1.65 vs. 2.01, = 0.208) or MACCEs (1.77 vs. 2.01, = 0.356), but was significantly associated wit