Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease

doi:10.1053/j.ajkd.2004.11.011

American Journal of Kidney Diseases

Volume 45, Issue 3, March 2005, Pages 494-501

https://doi.org/10.1053/j.ajkd.2004.11.011 Get rights and content

Background: Patients with end-stage renal disease on maintenance dialysis therapy have a high prevalence of cardiovascular risk factors and cardiovascular disease (CVD). A similar finding is noted in patients with chronic kidney disease (CKD). The important contributors are premature and accelerated atherosclerosis and vascular calcification. We assessed the severity of arterial stiffness in 102 patients with CKD by using pulse wave velocity (PWV) and sought to identify associated risk factors. Methods: PWV was measured by calculating the distance traveled by the flow wave and divided by the time delay. Correlations between PWV and traditional cardiovascular risk factors, estimated glomerular filtration rate (GFR) per 1.73 m², blood pressure (BP), and pulse pressure (PP) were analyzed. Results: PWV values in patients with CKD stages 1 to 2 and the age-matched control group were similar. There was a significant trend for a stepwise increase in PWV corresponding to advance in CKD stage (P < 0.0001). Univariate linear regression analysis showed that age, prior CVD, diabetes, hypertension, any high risk, estimated GFR per 1.73 m², systolic BP, and PP correlated with PWV. In the multivariate model, decreased estimated GFR per 1.73 m² and increased systolic BP were independently associated with increased PWV in patients with CKD (model R ² = 0.539; P < 0.0001). Conclusion: This is the first study to show a greater PWV in patients with more advanced CKD from stages 1 to 5. Estimated GFR per 1.73 m² and systolic BP were the major clinical determinants of arterial stiffness in patients with CKD independent of conventional risk factors for CVD.

Section snippets

Patients

In this cross-sectional study, 121 patients with CKD who received medical treatment and follow-up from September 2003 to May 2004 at National Cheng Kung University Hospital in Tainan, Taiwan, were evaluated. The diagnosis and classification of CKD were established according to criteria from the Clinical Practice Guidelines for Chronic Kidney Disease from the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative.²⁵ Estimated glomerular filtration rate (GFR) was derived from the

Results

Hypertension, dyslipidemia, the presence of 2 or more traditional cardiovascular risk factors, and any high risk were shown by more than half the total series of patients. Compared with subjects with CKD stages 1 to 2, patients with CKD stages 3 to 4 and stage 5 were older and had a greater prevalence of CVD, DM, and hypertension and higher systolic BP, PP, and PWV. Significant differences were found in age, hypertension, estimated GFR per 1.73 m², systolic BP, pulse pressure (PP), and PWV

Discussion

Atherosclerosis, a primary intimal disease characterized by the presence of plaques and occlusive lesions, is preceded by endothelial injury and dysfunction and may begin early in life, especially in patients with CKD. Increased arterial stiffness and decreased compliance are the major alterations in conduit function, which can be evaluated noninvasively by measuring the PWV of large arteries.27, 28 Mourad et al²⁴ reported a significant negative association between PWV and creatinine clearance

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Cited by (295)

Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease
2024, Nefrologia
El aumento de la rigidez arterial central (aórtica) tiene repercusiones hemodinámicas con efectos nocivos cardiovasculares y renales. En la enfermedad renal crónica (ERC) puede existir un aumento de la rigidez aórtica secundaria a múltiples alteraciones metabólicas, entre ellas la calcificación de la pared vascular (CV).
El objetivo de este estudio fue analizar la asociación de la rigidez aórtica y de la hemodinámica central con la presencia de CV en dos territorios: aorta abdominal (CAA) y arterias coronarias (CC).
Se incluyeron 87 pacientes con ERC estadios 3 y 4. Usando tonometría de aplanamiento se estudiaron la hemodinámica central y la rigidez aórtica. Esta se determinó mediante la velocidad de pulso carótida-femoral (Vp_c-f). A partir de la Vp_c-f se calculó el índice de la VP_c-f (iVp_c-f) que considera otras variables que influyen en la Vp_c-f, como edad, presión arterial, sexo y frecuencia cardiaca.
La presencia de CAA se valoró mediante radiografía lateral de columna lumbar calculándose el índice de Kauppila (iKauppila) y las CC mediante tomografía computarizada multidetección por el método de Agatston, calculándose su índice (iAgatston).
Para el estudio de la asociación entre iVp_c-f, iKauppila, iAgatston, presión aórtica central, parámetros clínicos y datos de laboratorio se usaron la regresión múltiple y la regresión logística. La capacidad discriminativa del iVp_c-f para evaluar la presencia de CAA y CC se determinó mediante el área bajo la curva (ABC) de ROC (receiver-operating characteristic).
La Vp_c-f y el iVp_c-f fueron 11,3 ± 2,6 m/s y 10,6 m/s, respectivamente. El iVp_c-f fue mayor cuando la ERC coexistía con diabetes mellitus (DM). Se detectaron CAA y CC en el 77% y el 87%, respectivamente.
La albuminuria (β = 0,13, p = 0,005) y el iKauppila (β = 0,36, p = 0,001) se asociaron de forma independiente con la magnitud del iVp_c-f. A su vez, el iVp_c-f (β = 0,39, p = 0,001), la DM (β = 0,46, p = 0,01) y el tabaquismo (β = 0,53; p = 0,006) se asociaron con la intensidad del iKauppila, pero solo el iVp_c-f predijo la existencia de CAA [(OR: 3,33 (IC 95%: 1,6-6,9; p = 0,001)].
El iKauppila se asoció de forma independiente con el iAgatston (β = 1,53, p = 0,001). La presencia de CAA identificó pacientes con CC con una sensibilidad del 73%, una especificidad del 100%, un valor predictivo positivo del 100% y un valor predictivo negativo del 38%.
El iVp_c-f predecía la presencia de CC [OR: 3,35 (IC 95%:1,04-10,2, p = 0,04)]. En las curvas ROC, usando el iVp_c-f, el ABC para las CAA y CC fue 0,82 (IC 95%: 0,71-0,93, p = 0,001) y 0,81 (IC 95%: 0,67-0,96, p = 0,02), respectivamente.
Cuando la ERC se asocia con DM hay un aumento de la rigidez aórtica determinada por el iVp_c-f. En la ERC estadios 3-4 son muy prevalentes las CAA y CC que, con mucha frecuencia, coexisten. El iVp_c-f se asocia de forma independiente con las CAA y CC, y puede ser útil para identificar pacientes con CV en estos territorios.
Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC).
The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries (CAC).
We included 87 patients with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pv_c-f) and Pv_c-f adjusted for age, blood pressure, sex and heart rate (Pv_c-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respectively. For the study of the association between iPv_c-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pv_c-f index for prediction of VC using receiver-operating characteristic (ROC).
Pv_c-f and Pv_c-f index were 11.3 ± 2.6 m/s and 10.6 m/s, respectively. The Pv_c-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively.
Albuminuria (β = 0.13, p = 0.005) and Kauppila score (β = 0.36, p = 0.001) were independently associated with Pv_c-f index. In turn, Pv_c-f index (β = 0.39, p = 0.001), DM (β = 0.46, p = 0.01), and smoking (β = 0.53; p = 0.006) were associated with Kauppila score, but only Pv_c-f index predicted AAC [OR: 3.33 (95% CI: 1.6–6.9; p = 0.001)].
The Kauppila score was independently associated with the Agatston score (β = 1.53, p = 0.001). The presence of AAC identified patients with CAC with a sensitivity of 73%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 38%.
The Vp_c-f index predicted the presence of CAC [OR: 3.35 (95% CI: 1.04–10.2, p = 0.04)]. In the ROC curves, using the Vp_c-f index, the AUC for AAC and CAC was 0.82 (95% CI: 0.71–0.93, p = 0.001) and 0.81 (95% CI: 0.67–0.96, p = 0.02), respectively.
When stage 3–4 CKD coexists with DM there is an increase in aortic stiffness determined by the Vp_c-f index. In stage 3–4 CKD, AAC and CAC are very prevalent and both often coexist. The Vp_c-f index is independently associated with AAC and CAC and may be useful in identifying patients with VC in these territories.
Effect of aging on the biaxial mechanical behavior of human descending thoracic aorta: Experiments and constitutive modeling considering collagen crosslinking
2023, Journal of the Mechanical Behavior of Biomedical Materials
Collagen crosslinking, an important contributor to the stiffness of soft tissues, was found to increase with aging in the aortic wall. Here we investigated the mechanical properties of human descending thoracic aorta with aging and the role of collagen crosslinking through a combined experimental and modeling approach. A total of 32 samples from 17 donors were collected and divided into three age groups: <40, 40–60 and > 60 years. Planar biaxial tensile tests were performed to characterize the anisotropic mechanical behavior of the aortic samples. A recently developed constitutive model incorporating collagen crosslinking into the two-fiber family model (Holzapfel and Ogden, 2020) was modified to accommodate biaxial deformation of the aorta, in which the extension and rotation kinematics of bonded fibers and crosslinks were decoupled. The mechanical testing results show that the aorta stiffens with aging with a more drastic change in the longitudinal direction, which results in altered aortic anisotropy. Our results demonstrate a good fitting capability of the constitutive model considering crosslinking for the biaxial aortic mechanics of all age groups. Furthermore, constitutive modeling results suggest an increased contribution of crosslinking and strain energy density to the biaxial stress-stretch behaviors with aging and point to excessive crosslinking as a prominent contributor to aortic stiffening.
Can Aortic and Renal Arteries Calcium Scores Be New Factors to Predict Post-Operative Renal Function After Nephron Sparing Surgery?
2022, Clinical Genitourinary Cancer
This study aims to investigate whether the calcification of renal arteries and aorta may be risk factors for developing chronic kidney disease (CKD) after Nephron sparing surgery (NSS).
The patients that underwent either open or laparoscopic NSS from 2000 to 2019 in 4 different centers were retrospectively assessed. Of these patients, 328 had a non-contrast-enhanced computer tomography.
Calcium scores of the renal arteries and abdominal aorta were measured in the non-contrast-enhanced images with the calcium score plugin (version 2.0) of Horos™. Univariate and multivariate logistic regression analysis was performed to determine significant risk factors for developing CKD at the last check-up. Roc curve analysis was performed to determine the optimal cut-off values of age and abdominal aorta calcium scores.
A total of 302 patients, of which 52 (16,6%) with CKD and 252 (83,4%) without CKD at the last check-up, were included in the analysis. The mean warm ischemia duration was significantly higher in patients with CKD (18,79±6,72 vs 16,38±5,57 minutes, p=0,016). The mean size of the tumor diameter and the number of the patients with ≥stage T1b were higher in the group with CKD (p=0,024 and 0,005, respectively). The median calcium scores of the aorta and renal arteries were higher in the group with CKD (p<0,001 and p<0,001, respectively). In multivariate analysis, age >60 years (OR:3,65, p=0,022), calcium score of the aorta (OR:4,07, p=0,029), tumor diameter (OR:1,03, p=0,026) and pre-operative CKD stage (OR:10,13, p<0,001) found the be significant factors for predicting last check-up CKD.
The calcium score of the aorta may be used as an additional risk factor to predict post-operative CKD risk after NSS with sensitivity over 80%.
Arterial stiffness and pulsatile hemodynamics in renal disease
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
Of the three main target organs vulnerable to damage from hypertension in humans, the kidneys, unlike the brain or heart reside below the diaphragms, thus, in the upright position they are exposed to higher ambient pressure loads compared to the cerebral or the coronary arteries. Moreover, the unique excretory function of the kidneys requires the ability to receive, filter, and process many liters of blood each hour. Sandwiched in between the afferent and efferent arterioles are more than a million glomeruli in each kidney, composed of a delicate set of capillaries which are responsible for the initial filtration that leads to urine formation. The kidneys, like the brain, are a marvel of low resistance vascular beds. Despite accounting for less than 2% of the body weight, they receive about 22% of the cardiac output. An intricate system of neural and myogenic reflexes which dampen the vagaries of pulsatile flow and the large artery stiffness that accompanies aging, and a variety of co-morbidities like diabetes. These reflexes are progressively lost as kidney fail, resulting in a vicious cycle of increasing kidney function loss. In this chapter we discuss the nature of the kidney circulation, the consequences on the kidney circulation of large artery stiffening, pathogenic pulsatile hemodynamics, and the associations of large artery stiffness with kidney function loss and cardiovascular diseases in chronic kidney disease.
Association between preoperative baseline pulse pressure and estimated pulse wave velocity and acute renal failure and mortality following colorectal surgery. A single-centre observational study
2021, Revista Espanola de Anestesiologia y Reanimacion
La elevada velocidad de onda de pulso es un parámetro hemodinámico considerado como un factor de riesgo para el desarrollo de alteraciones cardiovasculares, mientras que la presión de pulso es una variable predictora de complicaciones cardiovasculares y desarrollo de insuficiencia renal aguda tras cirugía, tanto cardíaca como no cardíaca. Nuestro objetivo fue determinar si la presión de pulso y la velocidad onda pulso estimada basales se asocian con complicaciones, insuficiencia renal y mortalidad durante los 30 días siguientes a cirugía colorrectal.
Estudio observacional retrospectivo. Fueron evaluados 816 pacientes adultos sometidos a cirugía colorrectal electiva, realizando un análisis de regresión logística multivariable para determinar si la presión de pulso y la velocidad onda pulso estimada basal se asociaban independientemente con las complicaciones, específicamente la insuficiencia renal y la mortalidad postoperatoria a 30 días, y si existían umbrales de presión de pulso y velocidad onda pulso estimada asociados a los resultados.
La presión de pulso basal fue de 56,00 mmHg (45,00;68,00) y la velocidad onda pulso estimada de 13,16 m/s (10,76;14,85). La presión de pulso basal no se asoció con complicaciones, insuficiencia renal aguda, ni mortalidad en el modelo univariante. Mientras que la velocidad onda pulso estimada basal tampoco se asoció con complicaciones, insuficiencia renal aguda, ni mortalidad. Una velocidad onda pulso estimada de 13,78 m/s predijo significativamente insuficiencia renal aguda (AUC 0,654 [0,588-0,720]) y mortalidad (AUC 0,698 [0,600-0,796]).
Ni la presión de pulso, ni la velocidad onda pulso estimada basal preoperatoria se asociaron con complicaciones, insuficiencia renal aguda, ni mortalidad postoperatoria. El umbral de velocidad onda pulso estimada preoperatoria de 13,78 m/s sirvió para discriminar aceptablemente un mayor riesgo de insuficiencia renal aguda y mortalidad postoperatoria.
Elevated pulse wave velocity is a haemodynamic parameter considered to be a risk factor for the development of cardiovascular alterations, while pulse pressure is a predictor of cardiovascular complications and development of acute renal failure after both cardiac and non-cardiac surgery. Our objective was to determine whether baseline pulse pressure and estimated pulse wave velocity are associated with renal failure and 30-day mortality following colorectal surgery.
Retrospective observational study. A total of 816 adult patients undergoing elective colorectal surgery were evaluated by performing multivariable logistic regression analysis to determine whether baseline pulse pressure and estimated pulse wave velocity were independently associated with complications, specifically renal failure and 30-day postoperative mortality, and whether pulse pressure and estimated pulse wave velocity thresholds correlated with outcomes.
Baseline pulse pressure was 56.00 mmHg (45.00;68.00) and estimated pulse wave velocity was 13.16 m/s (10.76;14.85). Baseline pulse pressure was not associated with acute renal failure or mortality in the univariate model. Baseline estimated pulse wave velocity was not associated with complications, acute renal failure, or mortality. An estimated pulse wave velocity of 13.78 m/s significantly predicted acute renal failure (AUC 0.654 [0.588-0.720]) and mortality (AUC 0.698 [0.600-0.796]).
Neither pulse pressure nor preoperative baseline estimated pulse wave velocity were associated with acute renal failure or postoperative mortality. The preoperative estimated pulse wave velocity threshold of 13.78 m/s predicted an increased risk of acute renal failure and postoperative mortality.
Association of Arterial Stiffness With Chronic Kidney Disease Progression and Mortality
2021, Heart Lung and Circulation
Citation Excerpt :
Accordingly, it has been hypothesised that moderately decreased renal function may be the cause of increased AS. It was also suggested that central AS may be an important pathophysiologic phenotype of vascular disease in CKD [24–27]. Several other mechanisms might be involved, including endothelial dysfunction, activation of the renin-angiotensin system (RAS), and qualitative and quantitative changes in the arterial wall such as glycation end-products, lipid peroxidation, elastin fragmentation, vascular smooth muscle cell hyperplasia, increased collagen, and decreased number of elastic fibres.
Chronic kidney disease (CKD) is a major public health concern. Despite many potentially life-threatening conditions that can accompany kidney disease, cardiovascular disease (CVD) remains the leading cause of death in these patients. Adjusted-for-age mortality from CVD in patients with end-stage renal disease is 10–30 times higher than in the general population. A decrease in renal function accelerates the development of cardiac pathology. Simultaneous exposure of CVD and CKD plays an important role in the relationship between arterial stiffness (AS) and estimated glomerular filtration rate. But there is a controversy as to whether the AS causes deterioration in kidney function, if renal dysfunction leads to AS, or the relationship is reciprocal. Hence, several studies that recruited high-risk populations reached a conclusion that comorbidities might lead to both AS and decline in kidney function over time. A number of studies have shown that several markers of AS, such as pulse pressure, central and peripheral pressure are associated with the development of CKD.
This review takes into account the theoretical background, current status, and future potential of the techniques that measure AS within context of CKD assessment and management.

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: Originally published online as doi:10.1053/j.ajkd.2004.11.011 on January 14, 2005.

: Supported in part by grant no. NSC92-2314-B-006-064 from the National Science Council, Taipei, Taiwan.

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Original investigationsPathogenesis and treatment of kidney disease and hypertensionStepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease

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Patients

Results

Discussion

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Kidney Int

J Am Coll Cardiol

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int Suppl

Kidney Int

Kidney Int

Accelerated atherosclerosis in prolonged maintenance hemodialysis

N Engl J Med

Arterial stiffening and vascular calcifications in end-stage renal disease

Nephrol Dial Transplant

Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis

N Engl J Med

Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease

Hypertension

Arterial media calcification in end-stage renal diseaseImpact on all-cause and cardiovascular mortality

Nephrol Dial Transplant

Impact of aortic stiffness on survival in end-stage renal disease

Circulation

Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease

J Am Soc Nephrol

Prognostic significance of arterial stiffness measurements in end-stage renal disease patients

Curr Opin Nephrol Hypertens

Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States

J Am Soc Nephrol

Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramiprilThe HOPE randomized trial

Ann Intern Med

Renal function and intensive lowering of blood pressure in hypertensive participants of the Hypertension Optimal Treatment (HOT) study

J Am Soc Nephrol

Original investigations
Pathogenesis and treatment of kidney disease and hypertension
Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease