Ana Cerqueira1,2,3, Janete Quelhas-Santos4, Susana Sampaio1,2,3, Inês Ferreira1,2,3, Miguel Relvas1, Nídia Marques1, Cláudia Camila Dias5,6, Manuel Pestana1,2,3. 1. Nephrology Department, Centro Hospitalar Universitário São João, 4200-319 Porto, Portugal. 2. Department of Medicine, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal. 3. 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. 4. Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal. 5. Department of Community Medicine Health Information and Decision, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal. 6. CINTESIS-Center for Health Technology and Services Research, 4200-250 Porto, Portugal.
Abstract
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 19-66) 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 ± 15.5 years, the mean eGFR was 54.9 ± 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 < 0.0001) and correlated negatively with age (r = -0.469, p < 0.0001), Charlson index (r = -0.399, p < 0.0001), systolic blood pressure (r = -0.256, 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 ± 0.40 vs. 2.01 ± 0.06, p = 0.493). In adjusted analysis, only age (β = -0.014, 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.
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 19-66) 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 ± 15.5 years, the mean eGFR was 54.9 ± 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 < 0.0001) and correlated negatively with age (r = -0.469, p < 0.0001), Charlson index (r = -0.399, p < 0.0001), systolic blood pressure (r = -0.256, 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 ± 0.40 vs. 2.01 ± 0.06, p = 0.493). In adjusted analysis, only age (β = -0.014, 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 patientsdied. 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.
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