Aortic pulse wave velocity in renal transplant patients

BACKGROUND: In subjects with end-stage renal disease (ESRD) undergoing hemodialysis, aortic pulse wave velocity (PWV) is increased independently of blood pressure level and mostly is a strong predictor of cardiovascular risk. Few studies on this subject have been performed in renal transplant patients. METHODS: Aortic PWV was determined noninvasively in 106 patients with kidney transplantation and treated using a standard immunosuppression protocol. Mean age was 43 +/- 14 years. During the follow-up period (mean duration 54.3 +/- 28.9 months), the following parameters were studied: characteristics of the renal graft, degree of renal insufficiency, number of acute rejections, cardiovascular risk factors, drug medications, and cardiovascular complications. RESULTS: Aortic PWV was increased in subjects with renal transplants independently of age and mean blood pressure. Acute renal rejection and smoking habits were the principal factors modulating together: the increase of aortic PWV and the reduction of the glomerular filtration rate (GFR). The latter renal parameter was also influenced by the donor age. Two main parameters were predictors of cardiovascular events: a past history of cardiovascular disease and the pulse pressure x heart rate product, the major mechanical consequence of increased PWV. CONCLUSION: In renal transplant subjects, tobacco consumption and mostly acute renal rejection modulate both aortic stiffness and chronic renal failure independent of blood pressure level and donor characteristics. Pulsatile stress mediates cardiovascular complications and predicts cardiovascular risk, particularly in the presence of increased heart rate.     

Relationship between serum bilirubin and albuminuria in patients with type 2 diabetes

Previous studies showed that low serum bilirubin concentrations are associated with increased risk of cardiovascular disease. To explore this further, we evaluated the relationships between serum bilirubin concentrations and the degree of urinary albumin excretion and other markers of subclinical atherosclerosis in 633 consecutive patients with type 2 diabetes. Multiple regression analysis showed that the serum bilirubin concentration was an independent determinant of and had a significant inverse correlation to the log urinary albumin excretion. Serum bilirubin concentrations were significantly lower in patients with than in those without cardiovascular disease. A significant inverse correlation was found between the serum bilirubin concentration and pulse wave velocity, while a significant positive correlation was found to the ankle-brachial index in a subgroup of 386 patients. Our study shows that the serum bilirubin level is associated with microalbuminuria and subclinical atherosclerosis in patients with type 2 diabetes.     

Aortic pulse wave velocity index and mortality in end-stage renal disease

BACKGROUND: Aortic pulse wave velocity (PWV) is a strong independent predictor of overall and cardiovascular mortality in patients with end-stage renal disease (ESRD). Nevertheless, because age, blood pressure, heart rate, and gender are strong determinants of both arterial stiffness and mortality, the individual relevance of PWV measurements remains controversial. METHODS: A cohort of 242 patients with ESRD undergoing hemodialysis was studied for a mean (+/- SD) duration of 78 +/- 46 months. At entry, together with standard clinical and biochemical analyses, PWV was measured using Doppler ultrasonography. On the basis of a nomogram established on 469 nonuremic subjects, a theoretical value of PWV was determined in ESRD patients according to their age, blood pressure, gender, and heart period. The PWV index (measured PWV - theoretical PWV) was then calculated for each individual ESRD patient. RESULTS: Based on Cox analysis, the PWV index, but neither pulse pressure nor cardiac mass, was a strong and independent predictor of both cardiovascular and overall mortality, together with age and time on dialysis before inclusion. Patients with positive (versus negative) PWV index had a twofold adjusted risk of mortality during the follow-up. Per each 1 meter/second PWV index increment, we observed a 34% (crude) and a 14% (adjusted) increase in both cardiovascular and overall mortality (P < 0.02 for all). CONCLUSION: In ESRD patients, the calculation of a PWV index provides information about cardiovascular and overall mortality risk with high predictive power, showing that PWV measurements provide discriminatory prognostic power over and above conventional cardiovascular risk factors.     

Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy

BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are heterogeneous and are scantily investigated, particularly if the patient has a lack of diabetic retinopathy. Therefore, we evaluated the structural background of albuminuria in a large consecutive group of Caucasian patients with type 2 diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three (27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these patients. An insufficient tissue sample was obtained in one patient. The biopsies were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex, age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/- 8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29 vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181 to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg), prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/- 2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were found between patients with and without diabetic glomerulopathy. CONCLUSIONS: Albuminuric patients with type 2 diabetes without diabetic retinopathy have a prevalence of biopsies with normal glomerular structure or nondiabetic kidney diseases of approximately 30%. A separation between diabetic and nondiabetic glomerular lesions was not possible based on demographic, clinical, or laboratory data. Consequently, such patients may require further evaluation, including a kidney biopsy.     

Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria.

BACKGROUND: Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial. METHODS: A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization. RESULTS: The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed. CONCLUSION: Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.     

Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity

BACKGROUND: Microalbuminuria appears to be a risk marker for atherosclerosis. However, little is known about the direct association between microalbuminuria and vascular wall properties. METHODS: Subjects were 306 type 2 diabetic patients with normoalbuminuria (N= 200) and microalbuminuria (N= 106). Those who had macroalbuminuria, atherosclerotic vascular disease, and/or ankle brachial index being less than 0.9 were not included. Brachial-ankle pulse wave velocity (PWV) was measured by automatic oscillometric method. Intima-media thickness (IMT) of the common carotid artery was measured using high-resolution B-mode ultrasonography and a computerized image-analyzing system. RESULTS: Average IMT, maximum IMT, and PWV were significantly higher in patients with microalbuminuria than in patients with normoalbuminuria. Both average and maximum IMT increased significantly as albuminuria increased in the microalbuminuric range. Average IMT and maximum IMT correlated significantly with PWV (P < 0.0001), although some patients exhibited increased levels of only PWV or IMT. By a multiple linear regression, age and albuminuria were independent predictors of IMT and PWV. Waist circumference was an independent predictor of IMT. Hypertension and hemoglobin A(1c) (HbA(1c)) were independent predictors of PWV. After adjustment for conventional cardiovascular risk factors including age, sex, waist circumference, HbA(1c), hypertension, hyperlipidemia, and smoking, albuminuria revealed a significant association with average IMT, maximum IMT, and PWV (P < 0.05, P < 0.0001, and P < 0.05, respectively). CONCLUSION: A slight elevation of albuminuria is a significant determinant of IMT and PWV independent of conventional cardiovascular risk factors in type 2 diabetic patients with no clinical nephropathy or any vascular diseases. This significant association might point to a link in the pathogenesis of atherosclerosis and diabetic nephropathy.     

Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes

There are no available data about the factors associated with diabetic nephropathy (DN) in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (66.2%) women and 52 (33.8%) men, with a mean age of 49.1 ± 10.1 years and a median duration of diabetes for 6 years. Hypertension was found in 60.8% of the patients and 16.3% had an HbA 1c <7%. Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. In the univariate analysis, the factors that were significantly associated with albuminuria were hypertension - both systolic and diastolic blood pressure levels, HbA 1c , retinopathy, duration of diabetes, and modality of treatment. Multiple logistic regression analysis indicated that hyper-tension was the main independent risk factor associated with albuminuria (OR 4.1, 95% CI 1.1- 15.0; P = 0.03). In conclusion, although albuminuria is common among Kuwaiti adults with type 2 diabetes, the prevalence is lower than that reported for other populations in spite of the poor glycemic control and the high prevalence of hypertension. Factors associated with albuminuria appear to be similar to other populations, and hypertension was the most independent factor. Early recognition and treatment of hypertension is an important strategy to prevent or delay DN as well as cardiovascular morbidity and mortality. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN.     

Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients

BACKGROUND: Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS: 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION: This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.     

Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.     

Rosiglitazone decreases albuminuria in type 2 diabetic patients

Thiazolidinediones are insulin-sensitizing compounds that reduce plasma glucose and improve the lipid profile of type 2 diabetic patients. We determined the effect of rosiglitazone in 15 type 2 diabetic patients and compared these results to 14 randomly assigned placebo patients. After 3 months, the urinary albumin to creatinine ratio was significantly decreased, while the glucose metabolic clearance rate, during insulin clamp, was significantly increased by rosiglitazone compared to the placebo group. Fasting free fatty acid and tumor necrosis factor-alpha (TNF-alpha) levels were significantly decreased, while the adiponectin concentration was significantly increased by rosiglitazone treatment. The percentage decrease in albuminuria correlated with the decrease in fasting plasma glucose, free fatty acids TNF-alpha and the increase in fat mass, plasma adiponectin, and glucose metabolic clearance rate. Stepwise linear regression analysis showed the decrease in TNF-alpha and the increase in adiponectin were independently associated with decreased albuminuria. Our study indicates that thiazolidinediones may be useful to prevent nephropathy in type 2 diabetic patients.     

Low serum endothelial cell-selective adhesion molecule predicts increase in albuminuria in type 2 diabetes patients

Purpose

The newly discovered endothelial cell-selective adhesion molecule (ESAM) stabilizes the interendothelial tight junction; it circulates in serum as a soluble fraction. In experimental diabetes, reduced ESAM expression in the kidney is associated with albuminuria. We investigated, for the first time, serum ESAM as a predictor of progression of kidney disease in type 2 diabetes (T2D).

Methods

T2D non-nephrotic patients with glomerular filtration rate (GFR) > 30 ml/min were included. History, medication and laboratory evaluation were assessed at inclusion and the end of study; ESAM was determined at baseline.

Results

Eighty-eight patients—mean age 63 ± 10.84 years, 49 (55.68 %) males—were prospectively followed up for 20 months. Baseline GFR was 76.37 ± 29.56 ml/min, and urinary albumin/creatinine ratio (UACR) 21.63(7.08–94.52) mg/g; ESAM was 12.85(6.13–19.83) ng/ml. Difference (Δ) in UACR between end of study and baseline was inversely related to serum albumin (r = ?0.27, p = 0.017) and ESAM (r = ?0.21, p = 0.047); ΔGFR correlated to glycated hemoglobin (r = 0.22, p = 0.05). In multiple regression, introducing variables susceptible to influence progression of kidney disease, ΔUACR was significantly related to log ESAM (p = 0.005) and ΔGFR to glycated hemoglobin (p = 0.016).

Conclusion

Serum ESAM is a predictor of worsening of albuminuria in T2D patients without advanced kidney disease.     

Arterial distensibility and pulse wave velocity in patients with primary hyperparathyroidism before and after parathyroidectomy

AIMS: There is evidence that secondary hyperparathyroidism alters arterial vessel wall properties. However, it is unclear whether effects of parathyroid hormone (PTH) on the vascular wall are direct or permissive and related to hypertension and renal failure. To assess early direct effects of PTH on large artery wall properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima-media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in patients with primary hyperparathyroidism (pHPT). METHODS: DC and IMT of the brachial and carotid artery were measured by echo-tracking and tonometry, PWV by the automatic Complior-device at baseline and 6 months after Ptx in 20 patients with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l). Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and hypercholesterolemia were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. RESULTS: Six months after Ptx, PTH decreased to normal; however, blood pressure levels and vessel wall parameter remained unchanged. At baseline, there were no significant differences in brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and 0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5 and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4 10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between patients and controls. CONCLUSIONS: Structural and viscoelastic properties of large arteries are not disturbed and not influenced by parathyroidectomy in patients with early pHPT devoid of hypertension and renal disease. We conclude that increased PTH levels per se are not associated with alterations of mechanical arteriall wall properties; permissive factors like renal insufficiency may be necessary to mediate vessel wall alterations in patients with hyperparathyroidism.     

New strategy to attenuate pulse wave velocity in haemodialysis patients.

BACKGROUND: Pulse wave velocity (PWV) is commonly elevated in haemodialysis (HD) patients having cardiovascular diseases. Disturbances in calcium-phosphate metabolism are among the established cardiovascular risk factors in HD patients. The present study was performed to assess the effect of sevelamer on PWV in HD patients. METHODS: Fifteen patients, who had been treated with calcium carbonate as a phosphate binder, were entered into the study. Changes in PWV during the 6 months before sevelamer administration were compared with PWV changes during 6 months of receiving sevelamer. Serum biochemistry parameters were also assessed. RESULTS: Compared with the preceding control period, the sevelamer period resulted in decreased serum calcium (9.9+/-0.1 to 9.6+/-0.1 mg/dl, n = 15; P<0.01) in association with reductions in oral calcium load (4.3+/-0.4 to 2.3+/-0.6 g/day; P<0.001). Serum phosphorus and whole parathyroid hormone remained unchanged. Sevelamer reduced serum total cholesterol (167+/-7 to 148+/-6 mg/dl; P<0.001) and LDL-cholesterol (85+/-8 to 65+/-7 mg/dl; P<0.001), without modifying HDL-cholesterol or triglycerides. Finally, sevelamer reversed the increase in PWV observed during the control period (from 46+/-16 to -20+/-9 cm/s/month; P<0.01). CONCLUSIONS: In chronic HD patients, sevelamer decreased serum total- and LDL-cholesterol as well as calcium. Moreover, our findings suggest that treatment with sevelamer attenuates the progressive increase in PWV observed during calcium carbonate treatment.     

Coronary artery calcification and aortic pulse wave velocity in chronic kidney disease patients

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of cardiovascular mortality and morbidity. Many complications arise in ESRD patients as a result of the twin arterial pathologies of atherosclerosis and arteriosclerosis. Part of this latter process is calcification of the arterial media, which is thought significantly to increase vascular stiffness. The aim of our study was to explore the relationship between measures of arterial stiffness-pulse wave velocity (PWV)-and the extent of calcification in the coronary arteries (CAC). METHODS: Over a period of 2 years 82 patients from our renal unit were invited to participate in our study. Sixty-two patients agreed to undergo electron beam computerized tomography (EBCT), and in 55 (38 males and 17 females), PWV measurements were made. EBCT and PWV measurements were done according to previously described protocols. RESULTS: The mean age of the 55 patients was 56.4 years. The mean duration of dialysis was 65.4 months, and the mean CAC score was 2551. The mean PWV was 9.13 m/s. PWV strongly correlated with total CAC even after correction for age, dialysis duration, and time averaged C-reactive protein (CRP) (P= 0.0001). CAC scores were significantly different when compared according to PWV tertiles (P= 0.0001). CONCLUSION: We have demonstrated that PWV is strongly related to the degree of EBCT-derived coronary artery calcium score in chronic kidney disease patients.