| Abstract|| |
Chronic kidney disease (CKD) is a growing problem worldwide. Clinical and epidemiologic studies have shown that structural and functional changes that occur in major arteries are a major contributing factor to the high mortality in uremic patients. Recent studies have shown a stepwise increase of the carotid-femoral pulse wave velocity (cfPWV) from CKD Stage 1 to Stage 5. We evaluated the cfPWV and augmentation index (AIx), as indirect markers of arterial stiffness in patients with nondiabetic CKD and compared the values with normal population; we also evaluated the relationship between various stages of CKD and arterial stiffness markers. This cross-sectional study was carried out in the Department of Nephrology for a duration of two years from January 15, 2012, to January 14, 2014. Fifty patients with nondiabetic CKD were studied along with 50 healthy volunteers who did not have CKD, who served as controls. Assessment of arterial stiffness (blood pressure, PWV, heart rate, aortic augmentation pressure, and AIx) was performed using the PeriScope device. PWV positively correlated with systolic and diastolic blood pressure, mean aortic arterial pressure, serum creatinine, and serum uric acid and negatively correlated with estimated glomerular filtration rate. Arterial stiffness increased as CKD stage increased and was higher in nondiabetic CKD group than in the general population. Arterial stiffness progressed gradually from CKD Stage 2 to 5, and then abruptly, in dialysis patients. Measures to decrease the arterial stiffness and its influence on decreasing cardiovascular events need further evaluation.
|How to cite this article:|
Mastanvalli B, Kumar KP, Madhav D, Venkata Pakki Reddy P L, Vali SM. Evaluation of arterial stiffness in nondiabetic chronic kidney disease patients. Saudi J Kidney Dis Transpl 2017;28:61-7
|How to cite this URL:|
Mastanvalli B, Kumar KP, Madhav D, Venkata Pakki Reddy P L, Vali SM. Evaluation of arterial stiffness in nondiabetic chronic kidney disease patients. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2017 May 26];28:61-7. Available from: http://www.sjkdt.org/text.asp?2017/28/1/61/198136
| Introduction|| |
Chronic kidney disease (CKD) is a growing problem worldwide and resulted in 735,000 deaths in 2010 globally. This increase in mortality was about 2-fold when compared with the mortality in the general population in 1990. Lower socioeconomic status is known to contribute to increased prevalence of CKD although there are still significant differences in the prevalence of CKD between African Americans and Caucasians when controlled for environmental factors. In addition, African Americans may have higher serum levels of human leukocyte antigens. Heat stress resulting from long hours of work at high temperatures , , and/or agricultural chemicals and other factors may be responsible for this. , A survey from India has stated that kidney diseases rank third among life-threatening diseases and estimated that approximately 200,000 people in India develop terminal kidney failure annually and only 22.5% receive dialysis treatment. The rationale for including individuals with GFR >60 mL/min/1.73 m is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of CKD: loss of kidney function and development of cardiovascular disease (CVD). CVD accounts for about 50% of deaths in these patients. , Clinical and epidemiologic studies have shown that structural and functional changes that occur in major arteries contribute to the high mortality in uremic patients. Macrovascular complications caused by atherosclerosis are rapid in onset and have a high degree of prevalence in end-stage renal disease patients. They are responsible, at least in part, for the high incidence of ischemic heart disease, congestive heart failure, sudden death, and stroke. Of equal or greater importance, however, is arteriosclerosis and arterial stiffening because they are prime determinants of left ventricular hypertrophy and patient survival on dialysis.
Generally, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are used in patients with CKD, as they have been found to slow the progression of the disease. , Renal transplantation increases the survival of patients with CKD significantly when compared with other therapeutic options. ,
Mechanisms implicated for increased stiffness in patients with uremia include chronic fluid overload, arterial calcifications, microinflammation, sympathetic nervous system over activity, activation of the renin-angiotensin- aldosterone system, increased lipid oxidation, oxidative stress, and abnormalities in the nitric oxide system. The result is the diffuse process of arteriosclerosis, characterized by stiffer arteries due to reduced arterial elasticity or compliance. These leads to a higher systolic blood pressure, lower diastolic blood pressure, and widened pulse pressure, all of which are known major determinants for high cardiovascular morbidity and mortality.
It is clear that arterial stiffness is not only determined by structural elements within the vessel wall and distending pressure but also by functional regulation by the sympathetic nervous system and endothelium of the vessel wall. Carotid-femoral pulse wave velocity (cfPWV), considered as the "gold standard" measurement of arterial stiffness, is a direct measurement, and it corresponds to the widely accepted propagative model of the arterial system.
Recent studies have shown a stepwise increase of the PWV from CKD Stage 1 to Stage 5. However, patients with diabetes mellitus were also included in these studies. Furthermore, we know that diabetes itself can be an independent risk factor for arterial stiffness. For this reason, we evaluated arterial stiffness at different stages of CKD in nondiabetic patients and to correlate with morbidity of the disease.
| Materials and Methods|| |
This cross-sectional study was carried out in the Department of Nephrology, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India, over a period of two years from January 15, 2012, and January 14, 2014. Fifty patients with nondiabetic CKD were taken as cases and fifty healthy volunteers who did not have CKD were taken as controls. The study protocol has been approved by the Narayana Medical College and Hospital Ethical Committee. On all patients and controls, assessment of arterial stiffness [blood pressure (BP), PWV, HR, aortic augmentation pressure (AoAP), and augmentation index (AIx)] was performed using the PeriScope device.
The inclusion criteria for the study were nondiabetic CKD patients in the age group of 20-60 years (both male and female). Patients having peripheral vascular diseases, diabetes mellitus, and those with cardiac conduction disorders were excluded from the study.
Assessment of arterial stiffness
This was measured in the supine position after a 10 min rest. Assessment of arterial stiffness (BP, PWV, HR, AoAP, and AIx) was performed using the PeriScope® device (Genesis Medical Systems Pvt. Ltd, Hyderabad, India), which has been shown to have a high degree of reproducibility for this purpose. Central aortic pressures and AIx were derived from brachial pressure waveforms and PWV, using a previously validated transfer function. With this transfer function, the system has been proven to give comparable results to other internationally known devices. The BP, HR, cfPWV, central aortic pressures, Aix, and AoAP were measured at baseline. Demographic, clinical, and laboratory records of the enrolled patients were also recorded.
| Statistical Analysis|| |
Categorical data are presented as actual numbers. Continuous variables are expressed as a mean ± standard deviation. For normally distributed data between groups, analysis was performed using unpaired t-test. For nonnormally distributed data, between-group analyses were performed using Mann-Whitney U- test. Categorical variables were analyzed with "Fisher's exact test." The Pearson correlation coefficient between PWV and other clinical variables was analyzed. For statistical significance, a two-tailed P <0.05 was considered statistically significant. The statistical analysis was carried out with Statistical Package for Social Sciences (SPSS) software version 18.0 (SPSS Inc, Chicago, IL, USA).
| Results|| |
The mean age (in years) of CKD and non- CKD patients was 44.54 ± 9.9 and 42.26 ± 10.0 years, respectively, without any statistical significance. The mean gender ratio in CKD and non-CKD groups was male:female, 36.14 and 42.8. The mean weight (in kg) of CKD and non-CKD patients was 57.20 ±12.0 and 64.34 ± 11.5 kg, respectively. The mean systolic BP (mm Hg) of CKD and non-CKD groups was 146.22 ± 21.6 and 131.88 ± 20.1, respectively, with P value of 0.001.
Parameters which showed statistical significance between predialysis patients and CKD patients on HD are shown in [Table 1].
|Table 1. Comparison of demographic, hemodynamic, vascular indices, and biochemical parameters between CKD-predialysis and hemodialysis groups (mean±SD).|
Click here to view
The mean AoAP (mmHg) of CKD and non- CKD patients was 18.81 ± 10.7 and 10.08 ± 4.8, respectively, with P value <0.0001. The mean AIx (%) of CKD and non-CKD patients was 43.77 ± 19.3 and 20.68 ± 9.3, respectively, with P value <0.0001. The mean cfPWV (cm/s) of CKD and non-CKD patients was 1256 ± 468 and 786 ± 126, respectively, with P value <0.0001. The mean serum creatinine (mg/dL) levels in CKD and non-CKD patients were 4.9 9 ± 3.26 and 0.83 ± 0.18, respectively, with P value <0.0001. The mean estimated glomerular filtration rate (eGFR) (mL/min) of CKD and non-CKD patients was 24.7 ± 18.9 and 103.9 ± 9.5, respectively, with P value <0.0001. The comparative measurements of hemodynamic and vascular indices among various stages of CKD have been shown in [Table 2], and the comparative measurements of biochemical parameters among various stages of CKD have been shown in [Table 3]. The comparison of vascular index parameters between CKD-predialysis and CKD-HD groups have been shown in [Figure 1].
|Figure 1. Comparison of vascular indices parameter (pulse wave velocity) between CKD-predialysis and|
CKD-HD group (mean±SD).
PWV: Pulse wave velocity, CKD: Chronic kidney disease, HD: Hemodialysis.
Click here to view
|Table 2. Comparison of hemodynamic and vascular indices among various stages of CKD-predialysis.|
Click here to view
|Table 3. Comparison of biochemical parameters between various stages of CKD-predialysis.|
Click here to view
PWV positively correlated with systolic BP (SBP), diastolic BP (DBP), aortic mean arterial pressure (MAP), serum creatinine, and serum uric acid and negatively correlated with eGFR ([Table 4]).
| Discussion|| |
In this study, we evaluated the arterial stiffness by measuring PWV in nondiabetic CKD population including CKD-5D and the same was compared with the general population which was used as control group. A total number of cases was fifty with equal number of controls. In our study, the mean age of CKD population was 44.54 ± 9.9 years, which much lower than in other studies. , , , , ,
Our study excluded the diabetic population because it is already well established that diabetes is an independent risk factor for arterial stiffness.
The arterial stiffness parameters were higher in the nondiabetic CKD group than the non- CKD group. These results are consistent with those in other studies. , , , ,
Arterial stiffness increases as CKD stage increases. In our study, the PWV gradually increased from CKD Stage 2 to Stage 5 nondialysis (950.5 → 1004.07 → 1038.1 cm/s) and showed a steep increase in the dialysis population (1038.1 → 1636.36 cm/s). Other studies also showed similar results. ,
Matsuda et al studied PWV in all stages of CKD and showed an increase in PWV from CKD 1-2 to CKD 3-5 (1281.6 ± 213.4 → 1674.3 ± 423.8). They also showed an increase in PWV from predialysis patients to those on dialysis (1533.8 ± 398.6 → 2283.8 ± 1562.0).
London et al, studied PWV only in the HD population and showed similar results. However, Shinohara et al, showed a decrease of PWV in dialysis patients compared with predialysis patients and attributed this to the removal of advanced glycation end products, homocysteine, and asymmetrical dimethyl arginine during HD. Unlike the study of Ashish Upadhya, where PWV correlated only with albuminuria but not with CKD, in our study, PWV correlated with all stages of CKD and dialysis patients.
| Conclusion|| |
Arterial stiffness (PWV) was higher in nondiabetic CKD group than in the general population. The arterial stiffness progressed gradually from CKD Stage 2 to 5, and then abruptly, in dialysis patients. PWV correlated positively with SBP, DBP, aortic MAP, serum creatinine, and uric acid and correlated negatively with eGFR. Measures to decreases the arterial stiffness and its influence on decreasing cardiovascular events need to be further evaluated.
Conflict of interest: None declared.
| References|| |
Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095- 128.
Appel LJ, Wright JT Jr., Greene T, et al. Longterm effects of renin-angiotensin system blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans. Arch Intern Med 2008;168:832-9.
Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J. End-stage renal disease in African-American and white men 16-year MRFIT findings. JAMA 1997;277: 1293-8.
Wesseling C, Crowe J, Hogstedt C, Jakobsson K, Lucas R, Wegman DH. The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: A call for interdisciplinary research and action. Am J Public Health 2013;103:1927-30.
Johnson RJ, Sánchez-Lozada LG. Chronic kidney disease: Mesoamerican nephropathy - New clues to the cause. Nat Rev Nephrol 2013;9:560-1.
Chavkin S, Greene R. Thousands of sugar cane workers die as wealthy nations stall on solutions. Center for Public Integrity, Dec. 2011 Dec;12
Orantes CM, Herrera R, Almaguer M, et al. Chronic kidney disease and associated risk factors in the Bajo Lempa region of El Salvador: Nefrolempa study, 2009. MEDICC Rev 2011;13:14-22.
National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease; 2002.
Bacchetta J, Pelletier S, Jean G, Fouque D. Immune, metabolic and epidemiological aspects of vitamin D in chronic kidney disease and transplant patients. Clin Biochem 2014; 47:509-15.
Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med 1981;71:456-67.
Raine AE, Margreiter R, Brunner FP, et al. Report on management of renal failure in Europe, XXII, 1991. Nephrol Dial Transplant 1992;7 Suppl 2:7-35.
Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697-701.
London GM, Guerin AP, Marchais SJ, et al. Cardiac and arterial interactions in end-stage renal disease. Kidney Int 1996;50:600-8.
Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term Ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet 1998;352:1252-6
Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999;354:359-64.
Maisonneuve P, Agodoa L, Gellert R, et al. Cancer in patients on dialysis for end-stage renal disease: An international collaborative study. Lancet 1999;354:93-9.
American Society of Nephrology. "Five Things Physicians and Patients Should Question". Choosing Wisely: An Initiative of the ABIM Foundation (American Society of Nephrology). www.choosingwisely.org
› About › News [Last retrieved on 2012 Aug 17].
Wang MC, Tsai WC, Chen JY, Huang JJ. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis 2005;45:494-501.
McIntyre NJ, Fluck RJ, McIntyre CW, Fakis A, Taal MW. Determinants of arterial stiffness in chronic kidney disease stage 3. PLoS One 2013;8:e55444.
Matsuda N, Takei T, Fujiu A, Ogawa T, Nitta K. Arterial stiffness in patients with nondiabetic Chronic Kidney Disease (CKD). J Atheroscler Thromb 2009;16:57-62.
Shinohara K, Shoji T, Tsujimoto Y, et al. Arterial stiffness in predialysis patients with uremia. Kidney Int 2004;65:936-43.
London GM, Marchais SJ, Safar ME, et al. Aortic and large artery compliance in endstage renal failure. Kidney Int 1990;37:137-42.
Nakagawa N, Takahashi F, Chinda J, et al. A newly estimated glomerular filtration rate is independently associated with arterial stiffness in Japanese patients. Hypertens Res 2008; 31:193-201.
Upadhyay A, Hwang SJ, Mitchell GF, et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol 2009;20:2044-53.
Kolla Praveen Kumar
Department of Nephrology, Narayana Medical College Hospital, Nellore - 524 003, Andhra Pradesh
[Table 1], [Table 2], [Table 3], [Table 4]