Abstract
The aim of this study was to assess the role of endothelial function measured by the reactive hyperemia index (RHI), arterial stiffness measured by the augmentation index (AIx), and Framingham’s cardiovascular disease (CVD) risk score (FRS) in kidney function decline in patients with chronic kidney disease (CKD). The RHI and AIx@75 (adjusted for 75 heart beats per minute), both derived from peripheral arterial tonometry (EndoPAT), were measured in 428 CKD patients aged 18 years old and older during hospitalization. We evaluated kidney function and its decline (incident ≥40% decline in estimated glomerular filtration rate [eGFR] or initiation of renal replacement therapy) associated with the RHI, AIx@75, and FRS during follow-up for a median of 36 months. The mean age of the participants was 56 years old, and 63.8% were men. In Spearman correlation analysis, the FRS, AIx@75, and RHI levels inversely correlated with eGFR. Over a median follow-up of 36 months, 122 participants experienced kidney function decline. In multivariate Cox analysis, only the FRS remained independently associated with the progression of kidney function (HR, 1.37; 95% CI, 1.14 to 1.64; P = 0.001). Multivariable-adjusted spline regression models showed a positive linear relationship between the FRS and the risk of kidney function decline (P-overall = 0.001, P-nonlinear = 0.701). However, adding the FRS to a model containing kidney function markers did not improve risk prediction for kidney outcome (category-free net reclassification improvement index [cf-NRI] = 0.179, P = 0.084; integrated discrimination improvement [IDI] = 0.017, P = 0.128). Additionally, the increased risk of the outcome associated with an elevated FRS was particularly evident among CKD patients with eGFR ≥60 ml/min/1.73 m2 (eGFR ≥ 60 ml/min/1.73 m2 vs.< 60 ml/min/1.73 m2, P for interaction = 0.022). Participants with higher FRS levels were at increased risk of kidney function decline, emphasizing the important role of traditional CVD risk factors in the progression of CKD.
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References
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease, and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013;382:339–52.
Bhatraju PK, Zelnick LR, Shlipak M, Katz R, Kestenbaum B. Association of soluble TNFR-1 concentrations with long-term decline in kidney function: the multi-ethnic study of atherosclerosis. J Am Soc Nephrol. 2018;29:2713–21.
Hirata Y, Sugiyama S, Yamamoto E, Matsuzawa Y, Akiyama E, Kusaka H, et al. Endothelial function and cardiovascular events in chronic kidney disease. Int J Cardiol. 2014;173:481–6.
Zanoli L, Lentini P, Briet M, Castellino P, House AA, London GM, et al. Arterial stiffness in the heart disease of CKD. J Am Soc Nephrol. 2019;30:918–28.
Mitchell GF. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol (1985). 2008;105:1652–60.
Sedaghat S, Mattace-Raso FU, Hoorn EJ, Uitterlinden AG, Hofman A, Ikram MA, et al. Arterial stiffness and decline in kidney function. Clin J Am Soc Nephrol. 2015;10:2190–7.
Peralta CA, Jacobs DR Jr., Katz R, Ix JH, Madero M, Duprez DA, et al. Association of pulse pressure, arterial elasticity, and endothelial function with kidney function decline among adults with estimated GFR >60 mL/min/1.73 m(2): the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis. 2012;59:41–9.
Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44:2137–41.
Mukai H, Svedberg O, Lindholm B, Dai L, Heimburger O, Barany P, et al. Skin autofluorescence, arterial stiffness and Framingham risk score as predictors of clinical outcome in chronic kidney disease patients: a cohort study. Nephrol Dial Transpl. 2019;34:442–8.
Kidney Disease: Improving Global Outcomes Diabetes Work G. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98:S1–S115.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.
D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 2008;117:743–53.
Levey AS, Inker LA, Matsushita K, Greene T, Willis K, Lewis E, et al. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis. 2014;64:821–35.
Dusing P, Zietzer A, Goody PR, Hosen MR, Kurts C, Nickenig G, et al. Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med (Berl). 2021;99:335–48.
Wang L, Huang X, He W, Liu W, Yang J. Digital microvascular reactivity does not decline with impaired renal function in chronic kidney disease. BMC Nephrol. 2019;20:288.
Cerqueira A, Quelhas-Santos J, Sampaio S, Ferreira I, Relvas M, Marques N, et al. Endothelial dysfunction is associated with cerebrovascular events in pre-dialysis CKD patients: A prospective study. Life. 2021;11.
Hamburg NM, Keyes MJ, Larson MG, Vasan RS, Schnabel R, Pryde MM, et al. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study. Circulation 2008;117:2467–74.
Brant LC, Hamburg NM, Barreto SM, Benjamin EJ, Ribeiro AL. Relations of digital vascular function, cardiovascular risk factors, and arterial stiffness: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort study. J Am Heart Assoc. 2014;3:e001279.
Koo BK, Chung WY, Moon MK. Peripheral arterial endothelial dysfunction predicts future cardiovascular events in diabetic patients with albuminuria: a prospective cohort study. Cardiovasc Diabetol. 2020;19:82.
Yang WI, Park S, Youn JC, Son NH, Lee SH, Kang SM, et al. Augmentation index association with reactive hyperemia as assessed by peripheral arterial tonometry in hypertension. Am J Hypertens. 2011;24:1234–8.
Harada M, Fujii K, Yamada Y, Tsukada W, Tsukada M, Hashimoto K, et al. Relationship between serum uric acid level and vascular injury markers in hemodialysis patients. Int Urol Nephrol. 2020;52:1581–91.
Nohria A, Gerhard-Herman M, Creager MA, Hurley S, Mitra D, Ganz P. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol (1985). 2006;101:545–8.
Schiffrin EL. Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature. J Cell Mol Med. 2010;14:1018–29.
Li Y, Yang Y, Wang W, Miao H, Zhang L, Cai G, et al. Peripheral arterial stiffness is correlated with intrarenal arteriolosclerosis according to biopsies from patients with kidney disease. Nephrology. 2020;25:371–8.
Lim LS, Ling LH, Cheung CM, Ong PG, Gong L, Tai ES, et al. Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy. Br J Ophthalmol. 2015;99:837–41.
Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300:H2–12.
Tajima E, Sakuma M, Tokoi S, Matsumoto H, Saito F, Watanabe R, et al. The comparison of endothelial function between conduit artery and microvasculature in patients with coronary artery disease. Cardiol J 2020;27:38–46.
Kim ED, Tanaka H, Ballew SH, Sang Y, Heiss G, Coresh J, et al. Associations between kidney disease measures and regional pulse wave velocity in a large community-based cohort: The Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2018;72:682–90.
Townsend RR, Wimmer NJ, Chirinos JA, Parsa A, Weir M, Perumal K, et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens. 2010;23:282–9.
Savant JD, Betoko A, Meyers KE, Mitsnefes M, Flynn JT, Townsend RR, et al. Vascular stiffness in children with chronic kidney disease. Hypertension 2017;69:863–9.
Tomiyama H, Tanaka H, Hashimoto H, Matsumoto C, Odaira M, Yamada J, et al. Arterial stiffness and declines in individuals with normal renal function/early chronic kidney disease. Atherosclerosis 2010;212:345–50.
Madero M, Peralta C, Katz R, Canada R, Fried L, Najjar S, et al. Association of arterial rigidity with incident kidney disease and kidney function decline: the Health ABC study. Clin J Am Soc Nephrol. 2013;8:424–33.
Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI, et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol. 2009;20:2044–53.
Jin B, Bai X, Han L, Liu J, Zhang W, Chen X. Association between kidney function and Framingham global cardiovascular disease risk score: a Chinese longitudinal study. PLoS One. 2014;9:e86082.
Lee C, Yun HR, Joo YS, Lee S, Kim J, Nam KH, et al. Framingham risk score and risk of incident chronic kidney disease: A community-based prospective cohort study. Kidney Res Clin Pr. 2019;38:49–59.
Chen SC, Su HM, Tsai YC, Huang JC, Chang JM, Hwang SJ, et al. Framingham risk score with cardiovascular events in chronic kidney disease. PLoS One. 2013;8:e60008.
Funding
This study was supported by the Natural Science Foundation of China (NSFC) (82170686), the National Key Research and Development (R&D) Program of China (2018YFA0108803), and the Science and Technology Project of Beijing, China (D181100000118004).
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GY. Cai and YS. Li contributed to the research idea and study design; YS. Li, XR. Guo and S. Liang collected the data; YS. Li and P. Chen performed the statistical analyses; YS. Li, XR. Guo, Y. Zheng, and P. Li contributed to the interpretation of the results; and GY. Cai, J. Wu and XM. Chen provided supervision or mentorship.
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Li, Y., Guo, X., Liang, S. et al. Endothelial function, arterial stiffness and Framingham risk score in chronic kidney disease: A prospective observational cohort study. Hypertens Res 46, 868–878 (2023). https://doi.org/10.1038/s41440-022-01141-6
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DOI: https://doi.org/10.1038/s41440-022-01141-6
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