Inhibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene

OBJECTIVE: To define the distribution and determinants of cardiovascular disease events among participants undergoing long-term antihypertensive therapy, and to stratify them into risk groups on the basis of pretreatment clinical profiles. DESIGN: A prospective cohort study of participants in a worksite-based antihypertensive treatment program in New York city (1973-1994). PATIENTS: We studied 8690 systematically treated patients who had at least 6 months of follow-up (average of 5.7 years) and, at entry, had had a systolic blood pressure of > or = 160 mmHg or a diastolic blood pressure of > or = 95 mmHg (after 1992 > or = 140/90 mmHg), or had been being administered antihypertensive medication. MAIN OUTCOME MEASURES: Blood pressure and incidence of morbid and mortal cardiovascular events. RESULTS: Blood pressure control (to 140 +/- 3/87 +/- 7 mmHg) was achieved by the first year and maintained through 18 years of therapy. In nearly 50,000 person-years of follow-up, there were 468 cardiovascular disease events [myocardial infarction including revascularization (282), strokes (93), congestive heart failure (30) and other cardiovascular deaths (63)]. Deaths from cardiovascular disease events accounted for 68% of all deaths. Myocardial infarction was most common throughout, but congestive heart failure incidence surpassed stroke incidence after 10 years. A scheme for risk stratification was constructed after analysis of the independent association of baseline factors and incident cardiovascular events. Upon the basis of ease of ascertainment and their demonstrated associations with occurrence of cardiovascular disease during treatment, we selected five pretreatment factors (history of heart attack, stroke, diabetes, age > or = 55 years and pulse pressure > or = 60 mmHg) to stratify patients into four groups. Those with no risk factor had a low risk (n=2999), those with one had a moderate risk (3042), those with two had a high risk (2237), and those with three or more had a very high risk (412). Overall, the unadjusted rates of incidence of cardiovascular disease events per 1000 person-years for patients in very high and low risk groups differed by factors of six and 14 for men and women, respectively. CONCLUSION: These results demonstrate that long-term control of blood pressure can be achieved in a general population. Nevertheless, cardiovascular disease events still accounted for most morbidity and mortality among these 'recovered' hypertensive patients. At entry, on the basis of readily identifiable characteristics, it was possible to stratify patients according to likelihood of subsequent events occurring despite control of blood pressure. This scheme could provide the basis for targeting more aggressive therapy where the potential for further cardioprotection is greatest.     

Studies of the vessel wall properties in hemodialysis patients

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carotid atherosclerosis in renal transplant recipients

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.     

High pressure NMR study of a small protein, gurmarin

The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood pressure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of aortic calcification (P=.0004), and the prevalence of diabetes mellitus (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (P<.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (P=.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs.     

Albuminuria and glycemic control. The significance for mortality in non-insulin-dependent diabetes mellitus]

The impact of microalbuminuria and macroalbuminuria on mortality was evaluated prospectively in 328 Caucasian patients with non-insulin-dependent diabetes mellitus (NIDDM) followed for five years. One hundred and ninety-one patients with normoalbuminuria (albumin excretion rate (AER) < 30 mg/24 h), 86 patients with microalbuminuria (AER 30-299 mg/24 h), and 51 patients with macroalbuminuria (AER > or = 300 mg/24 h) all less than 66 years old at start of the study were followed from 1987 until death or until 1 January 1993. Eight percent of patients with normoalbuminuria, 20% of patients with microalbuminuria, and 35% of patients with macroalbuminuria had died, predominantly from cardiovascular disease. Significant predictors of all-cause mortality included preexisting coronary heart disease, AER, HbA1c level and age. Significant predictors of cardiovascular mortality included preexisting coronary heart disease, macroalbuminuria, HbA1c level and systolic blood pressure. Abnormally elevated urinary albumin excretion and poor glycaemic control indicate a substantially increased all-cause, mainly cardiovascular, mortality risk in NIDDM patients.     

Menaquinone-dependent succinate dehydrogenase of bacteria catalyzes reversed electron transport driven by the proton potential

BACKGROUND: The cushioning function of the arterial system is altered in patients with end-stage renal failure. The role of hyperparathyroidism for the altered vessel wall properties of large arteries not known. METHODS: To exclude the confounding effects of fluid volume changes and hypercirculation as well as uremic toxicity on vessel wall properties from those of hyperparathyroidism, the present study was conducted in 54 normotensive renal transplant recipients with good graft function, three to six months after transplantation. The vessel wall properties of the common carotid artery were investigated in 32 of them, who had increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter, SEM), and compared to those of 22 control recipients of same age with normal plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by Doppler analysis of the vessel wall movements, blood pressure was determined by sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in patients with normal plasma iPTH levels (NS). There was no difference in enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal transplant recipients with hyperparathyroidism as compared with the control patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28 microns, P < 0.05) and distensibility coefficient of the common carotid artery (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared with the control patients. Multiple regression analysis showed that the distensibility coefficient of the common carotid artery was negatively correlated with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH levels (P < 0.05). The effects of plasma iPTH levels were not related to serum calcium concentrations or to differences in the enddiastolic diameter of the common carotid artery. CONCLUSIONS: The data suggest that secondary hyperparathyroidism can affect the cushioning function of larger arteries in patients with end-stage renal failure independently of high blood pressure.     

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.     

Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study

BACKGROUND: The aim of this study was to compare the risk conferred by white-coat versus sustained mild hypertension for the development of cardiovascular disease. METHODS AND RESULTS: Patients (n=479) who underwent 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of a persistently elevated clinic systolic blood pressure of 140 to 180 mm Hg were followed up for the development of subsequent cardiovascular events during a 9.1+/-4. 2-year period. White-coat hypertension, defined as a clinic systolic blood pressure of 140 to 180 mm Hg associated with a 24-hour ambulatory systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg, was present in 126 patients, and the remainder had sustained mild hypertension. A subgroup of patients without complications underwent follow-up echocardiography and carotid ultrasound. White-coat hypertensives were younger (44+/-12 versus 52+/-10 years, respectively; P<0.001) and had a significantly lower incidence of cardiovascular events (1.32 versus 2.56 events per 100 patient-years, respectively; P<0.001) than sustained hypertensives. Multivariate analysis revealed age (P=0.002), sex (P=0.007), race (P=0.001), smoking (P=0.005), and the presence of white-coat hypertension (hazard ratio, 0.29; 95% CI, 0.09 to 0.90; P=0.04) to be independent predictors of subsequent cardiovascular events. Subgroup analysis in patients without complications revealed a lower incidence of left ventricular hypertrophy and lesser degrees of carotid hypertrophy in the white-coat group. CONCLUSIONS: These findings indicate a relatively benign outcome in white-coat hypertension compared with sustained mild hypertension.     

Stability of iodinated contrast media in UV-laser irradiation and toxicity of the photoproducts]

BACKGROUND: While elevated levels of serum creatinine have been shown to be a risk factor for diminished survival after stroke, it is unknown how renal replacement therapy may affect the outcome. METHODS: Strokes occurring in 26 consecutive patients undergoing hemodialysis at our institution were reviewed and clinical and laboratory variables and outcome were compared with those of patients who had a stroke but had normal renal function. RESULTS: Twenty-four strokes in the patients undergoing hemodialysis were ischemic while only 2 were hemorrhagic. Virtually all the patients had hypertension, half had diabetes mellitus, and most had some prior evidence of cardiovascular disease at the time of their stroke. Fifty percent of the patients undergoing hemodialysis had a good outcome (defined as being discharged home) while the remainder had a poor outcome (defined as dying or being discharged to a nursing facility). The combined presence of hypertension and coronary artery disease had a sensitivity of 91.2% for identifying patients with a poor outcome, while male sex, the presence of coronary artery disease, and the combined presence of hypertension, coronary artery disease, and/or congestive heart failure had sensitivities greater than 80% but low specificity. The outcome of patients undergoing hemodialysis was comparable with that of a control group of patients who had a stroke but had normal renal function, although the length of hospital stay was greater (mean [+/-SEM] 29.8+/-6.4 days vs 12.7+/-1.1 days, respectively; P<.01). CONCLUSIONS: Hospitalized patients undergoing hemodialysis in whom stroke occurs appear to have as good an outcome as that of patients with normal renal function, although they are hospitalized longer. In addition, certain clinical variables seem to be associated with a worse outcome. Aggressive measures to prevent and treat stroke seem as warranted for patients undergoing hemodialysis as for patients with normal renal function, although interventions to reduce the length of hospital stay are needed.     

Radiation exposure of the population by roentgen diagnosis. II. The collective effective dosage of the population in former East Germany caused by 1987/1988 roentgen diagnosis

OBJECTIVES: To examine the relations between the development of neurologic events and the following variables: degree of stenosis of the contralateral carotid artery, prior neurologic symptoms and stump pressure of the ipsilateral internal carotid artery in patients undergoing carotid endarterectomy under regional anesthesia. PATIENTS AND METHODS: We undertook a prospective study of 92 patients undergoing carotid endarterectomy with a blockade of the superficial and deep cervical plexus. Neurological integrity was assessed and internal carotid artery stump pressure was monitored. Contralateral carotid artery stenosis and neurologic disease present before surgery were studied. RESULTS: Neurologic events developed when the carotid artery was clamped in 9.7% of patients. Mean stump pressure was significantly lower in symptomatic patients (43 +/- 11 mmHg) than in asymptomatic patients (74.6 +/- 24 mmHg) (p < 0.001). Neurologic symptoms developed during clamping of the carotid in 27.2% of the patients with stump pressure less than or equal to 50 mmHg, but in only 4.2% of those with stump pressure surpassing 50 mmHg. Stump pressure was significantly lower in patients with contralateral carotid stenosis. The incidence of neurologic events during clamping was unrelated to contralateral carotid condition, however. Likewise, neurologic symptoms before surgery was also unrelated. In six of the nine patients with neurologic events, internal carotid stump pressure was less than or equal to 50 mmHg, indicating that the sensitivity of this parameter to the development of neurologic events in our series was 66%. CONCLUSIONS: Although internal carotid artery stump pressure identifies a subset of patients likely to have a higher incidence of neurologic events during carotid artery clamping, it can not be considered the only criterion for placement of an intraluminal shunt to prevent such events. The state of the contralateral carotid artery and preexisting neurologic symptoms are not objective screening criteria for identifying patients at high risk of neurologic events during carotid clamping.     

LDL-unbound apolipoprotein(a) and carotid atherosclerosis in hemodialysis patients

High lipoprotein(a) [Lp(a)] plasma concentrations, which are genetically determined by apo(a) size polymorphism, are directly associated with an increased risk for atherosclerosis. Patients with end-stage renal disease (ESRD), who show an enormous prevalence of cardiovascular disease, have elevated plasma concentrations of Lp(a). In recent studies we were able to show that apo(a) size polymorphism is a better predictor for carotid atherosclerosis and coronary artery disease in hemodialysis patients than concentrations of Lp(a) and other lipoproteins. Less than 5% of apo(a) in plasma exists in a low-density lipoprotein (LDL)-unbound form. This "free" apo(a) consists mainly of disintegrated apo(a) molecules of different molecular weight, ranging from about 125 to 360 kDa. LDL-unbound apo(a) molecules are elevated in patients with ESRD. The aim of this study was therefore to investigate whether the LDL-unbound form of apo(a) contributes to the prediction of carotid atherosclerosis in a group of 153 hemodialysis patients. The absolute amount of LDL-unbound apo(a) showed a trend to increasing values with the degree of carotid atherosclerosis, but the correlation of Lp(a) plasma concentrations with atherosclerosis was more pronounced. In multivariate analysis the two variables were related to neither the presence nor the degree of atherosclerosis. Instead, the apo(a) phenotype took the place of Lp(a) and LDL-unbound apo(a). After adjustment for other variables, the odds ratio for carotid atherosclerosis in patients with a low molecular weight apo(a) phenotype was about 5 (p<0.01). This indicates a strong association between the apo(a) phenotype and the prevalence of carotid atherosclerosis. Finally, multivariate regression analysis revealed age, angina pectoris and the apo(a) phenotype as the only significant predictors of the degree of atherosclerosis in these patients. In summary, it seems that LDL-unbound apo(a) levels do not contribute to the prediction of carotid atherosclerosis in hemodialysis patients. However, this does not mean that "free", mainly disintegrated, apo(a) has no atherogenic potential.     

Residual urine in 75-year-old men and women. A normative population study

To evaluate the therapeutic effects of high dose pulse oral calcitrol, 3.5 micrograms calcitrol three times a week and calcium carbonate were administered to 13 patients with end-stage renal disease on chronic hemodialysis with hyperparathyroidism refractory to conventional calcitrol therapy. Serum parathyroid hormone and osteocalcin were detected by radioimmunoassay. Serum parathyroid hormone level of the patients decreased from 1111 +/- 344 ng/L to 492 +/- 218 ng/L by 57.5 +/- 11.5 percent (P < 0.01) in 6 months after the beginning of treatment. Both serum alkaline phosphatase and osteocalcin levels declined markedly, and correlated positively with that of parathyroid hormone. Plasma calcium concentration was markedly elevated, but no obvious increase of plasma phosphate was found. High dose pulse oral calcitrol was effective on secondary hyperparathyroidism. During the course of treatment timely and individual adjustment of calcitrol dose and dialysate calcium concentration is essential.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions between dietary fat type and xylanase supplementation when rye-based diets are fed to broiler chickens 2. Performance, nutrient digestibility and the fat-soluble vitamin status of livers

We analyzed retrospectively the outcome of 169 patients in chronic hemodialysis (CHD), divided into four groups: 1) 24 patients with diabetic nephropathy (age 53.7 +/- 11 years); 2) 19 with polycystic kidney disease (age 55.3 +/- 9 years) 3) 43 patients older than 60 when starting chronic hemodialysis with etiologies different from diabetes and polycystic kidney disease (age 69.2 +/- 5.8 years) and 4) 83 patients younger than 60 with diverse etiologies (age 42.8 +/- 12.4 years). In groups 1, 2 and 3 serum creatinine, arterial hypertension at the beginning, morbility, mortality and its causes were registered. In group 1, the prevalence of severe diabetic retinopathy and cardiovascular disease at the beginning were also analyzed. In all groups survival was determined. Of the diabetics, 92% presented severe diabetic retinopathy and 88% cardiovascular disease. The prevalence of hypertension was 100, 74 and 67% in groups 1, 2 and 3, respectively (p = 0.13). Twelve diabetics died before the first year of treatment; there was no difference in creatinine, age, cardiovascular disease, severe retinopathy and hypertension with those who lived more than one year. The percentage of time in risk hospitalized and the days/patients/year hospitalized were significantly different between group 1 and 3 and group 2 (p < 0.001). Patients were hospitalized for similar causes in groups 1 and 3: the initiation of CHD, cardiovascular and neurological diseases. The main causes of death in groups 1 and 3 were: cardiovascular disease and sudden death at home. Survival was better in group 2 compared with group 1 (p = 0.0014) but was similar between groups 1 and 3 (p = 0.21) even though there was a difference of 15 years between them. The Cox's proportional hazard model identified as risk factors diabetes, age, year of starting chronic hemodialysis and hospitalization episodes, adjusted for covariates. The outcome of diabetic patients in chronic hemodialysis showed high morbidity and mortality and was quite similar to that of elderly patients.     

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients

The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 +/- 3/80 +/- 2 mm Hg at entry and 133 +/- 3/82 +/- 2 mm Hg after 2 years in the normotensive group, 146 +/- 4/90 +/- 3 mm Hg at entry and 145 +/- 3/87 +/- 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 +/- 1.3 10(-3)/kPa before, 15.1 +/- 1.2 10(-3)/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (DC 19.0 +/- 1.4 10(-3)/kPa before, DC 17.8 +/- 1.3 10(-3)/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). The results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. Since BP levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.     

Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis

Contact to artificial surfaces during hemodialysis activates leukocytes, which then form oxidized arachidonic acid products and free radicals. This might promote the oxidative modification of low-density lipoproteins (LDL) that play a key role in the initiation of atherosclerosis. Thus, leukocyte activation could specifically contribute to the high mortality from atherosclerotic complications on long-term hemodialysis. Therefore monitored LDL and high-density lipoprotein (HDL) resistance to copper-stimulated oxidation in patients with end-stage renal disease on maintenance hemodialysis with cellulose acetate or polysulfone membranes (n = 12), in patients with chronic renal failure (n = 13) and in healthy controls (n = 12). Six of the dialysis patients were restudied during a single cuprophane dialysis. Circulating leukocytes were reversibly reduced early in hemodialysis with cellulose acetate (minimum, 83.6% +/- 7.4% of baseline values at 30 minutes after dialysis start), polysulfone (minimum, 80.4% +/- 10.5% at 15 minutes; P < 0.05) and cuprophane (minimum, 24.5% +/- 8.5% at 60 minutes; P < 0.0001). Despite the leukocyte activation, LDL oxidation lag time was not shortened in comparison with healthy controls and was even prolonged at the end of cellulose acetate (P < 0.05) and cuprophane (P < 0.05) dialysis. HDL oxidation lag time increased (12.6% +/- 0.9%; P < 0.0001) 15 to 60 minutes after start of hemodialysis and returned to predialysis values thereafter. In patients with chronic renal failure, the lag time of HDL oxidation was significantly prolonged (13.34 minutes +/- 0.9) compared with healthy controls (10.91 +/- 2.0 minutes; P < 0.01) as well as compared with the dialysis patients at baseline (9.9 minutes +/- 1.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the pharmacokinetics, dialysability, and safety of gadodiamide injection in patients with severely reduced renal function not treated with renal replacement therapy and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. MATERIALS AND METHODS: Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). RESULTS: Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An average of 65% of the gadodiamide injected was eliminated during a hemodialysis session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the total amount of gadodiamide was excreted; this reflects the low peritoneal clearance. In all patients, no metabolism or transmetallation of gadodiamide was found. There were no contrast material-related adverse events. CONCLUSION: Gadodiamide is dialysable and can safely be used in patients with severely impaired renal function or those undergoing hemodialysis or continuous ambulatory peritoneal dialysis. No precautions to increase the elimination are necessary.     

Can fingernail creatinine concentrations be used to predict duration of azotemia?

Clinical use of fingernail creatinine estimation to predict duration of azotemia is yet to be validated. We studied the fingernail creatinine concentrations in 48 subjects: seven controls, nine with acute renal failure, five with rapidly progressive glomerulonephritis, 12 with chronic renal failure and 15 with end-stage renal failure on maintenance hemodialysis. The creatinine concentration in aqueous eluates of powdered nail clippings was determined by the alkaline picrate reaction. The mean fingernail creatinine concentration was significantly higher in patients with chronic renal failure (93.7 +/- 83.7 micrograms/g) and end-stage renal disease on maintenance hemodialysis (118.4 +/- 46.8 micrograms/g) as compared to those with acute renal failure (36.6 +/- 23.7 micrograms/g) and rapidly progressive glomerulonephritis (35.8 +/- 20.6 micrograms/g). The creatinine concentrations did not differ significantly between normal subjects (27.2 +/- 28.7 micrograms/g) and those with acute renal failure and rapidly progressive glomerulonephritis. However because of large variability in the values of fingernail creatinine concentrations within each group, the test lacked specificity. Therefore, this investigation is an unreliable indicator of duration of azotemia in individual patients and is not likely to be of much clinical use.     

Inflammation enhances cardiovascular risk and mortality in hemodialysis patients

BACKGROUND: Atherosclerosis, a major problem in patients on chronic hemodialysis, has been characterized as an inflammatory disease. C-reactive protein (CRP), the prototypical acute phase protein in humans, is a predictor of cardiovascular mortality in the general population. We hypothesize that several of the classic, as well as nontraditional, cardiovascular risk factors may respond to acute phase reactions. An activated acute phase response may influence or predict cardiovascular risk. METHODS: In 280 stable hemodialysis patients, serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were determined in relation to CRP and serum amyloid A (SAA), two sensitive markers of an acute phase response. Mortality was monitored prospectively over a two year period. RESULTS: Serum CRP and SAA were found to be elevated (more than 8 and more than 10 mg/liter, respectively) in 46% and 47% of the patients in the absence of clinically apparent infection. Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a), higher plasma fibrinogen, and lower serum levels of high-density lipoprotein cholesterol, apo A-I, and Salb than patients with normal CRP or SAA. The rise in Lp(a) concentration was restricted to patients exhibiting high molecular weight apo(a) isoforms. During follow-up, 72 patients (25.7%) had died, mostly due to cardiovascular events (58%). Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP (31% vs. 16%, P < 0.0001, and 23% vs. 5%, P < 0.0001, respectively) or SAA (29% vs. 19%, P = 0.004, and 20 vs. 10%, P = 0.008, respectively) and were also higher in patients with Salb of lower than 40 g/liter (44% vs. 14%, P < 0.0001, and 34% vs. 6%, P < 0.0001, respectively). Univariate Cox regression analysis demonstrated that age, diabetes, pre-existing cardiovascular disease, body mass index, CRP, SAA, Salb, fibrinogen, apo A-I, and Lp(a) were significantly associated with the risk of all-cause and cardiovascular mortality. During multivariate regression analysis, SAA, fibrinogen, apo A-I, and Lp(a) lost their predictive values, but age and CRP remained powerful independent predictors of both overall death and cardiovascular death. CONCLUSION: These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response, which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death. The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. A successful treatment of the inflammatory condition may improve long-term survival in these patients.     

Prevalence of renal disease in elderly hypertensive patients with cardiovascular problems

Renal vascular damage caused by arterial hypertension participates in the alterations to systemic vascular function and structure. Nephrosclerosis seems to run in parallel with systemic atherosclerosis, which accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function have to be considered in any stratification of cardiovascular risk in hypertensive patients.