Duration Of Dialysis Treatment Research Articles

Impaired renal function and duration of dialysis therapy are associated with oxidative stress and proatherogenic cytokine levels in patients with end-stage renal disease

Objectives: The present study was undertaken to clarify the role of the impaired renal function and the dialysis therapy on plasma levels of proatherogenic cytokines and Cu/Zn superoxide dismutase (Cu/Zn SOD)—as a marker of oxidative stress (SOX) in uraemia. Design and methods: We have measured the levels of Cu/Zn SOD, monocyte chemoattractant protein-1 (MCP-1) macrophage inflammatory proteins (MIP-1α, MIP-1β) and vascular endothelial growth factor (VEGF) in the plasma of predialysis (CRF) ( n = 42), on maintenance hemodialysis (HD) ( n = 25) or peritoneal dialysis (PD) ( n = 45) patients and in the healthy volunteers ( n = 20). Results: The increase in Cu/Zn SOD levels was in PD and HD patients compared to controls (215.56 ± 125.18 and 356.28 ± 122.57 versus 53.53 ± 23.65 ng/ml, respectively). In plasma of the CRF, PD and HD subjects we have also observed the significant increase in the levels of MIP-1β: [31.5 (2–149), 33.0 (1–203) and 76.0 (9–345), respectively]; MCP-1 (616.50 ± 240.15, 943.64 ± 348.99 and 968.50 ± 355.85, respectively) and VEGF (387.93 ± 184.63, 371.56 ± 125.18 and 645.56 ± 136.30, respectively) compared to healthy people. In the predialysis group, creatinine clearance correlated with Cu/Zn SOD and cytokine levels. Moreover, the cytokine levels were also associated with age. In dialysis patients, the correlations were between duration of dialysis treatment and both Cu/Zn SOD and cytokine levels. There was also a direct relationship between Cu/Zn SOD and both MIP-1β and VEGF levels. Conclusions: This study has shown that impaired renal function, age and duration of dialysis treatment are associated with increased oxidative stress and proatherogenic cytokine levels in uremic patients.

Hemodialysis and Peritoneal Dialysis

This study was undertaken to examine patient satisfaction with peritoneal dialysis (PD) and hemodialysis (HD) therapies, focusing attention on the positive and negative impact of the therapies on patients' lives. Patients were recruited from a free-standing PD unit and two free-standing HD units. A total of 94% (n = 62) of eligible PD and 84% (n = 84) of eligible HD patients participated. HD patients were significantly older and had higher Charlson Comorbidity Index scores than the PD patients, but there were no differences in duration of dialysis treatment, prevalence of diabetes, educational backgrounds, or home situations. Patients were asked to rate their overall satisfaction with and the overall impact of their dialysis therapy on their lives, using a 1 to 10 Likert scale. In addition, patients were asked to rate the impact of their therapy on 15 domains that had been cited previously as being important for patients' quality of life. The mean satisfaction score for PD patients (8.02 +/- 1.41) was higher than for HD patients (7.4 +/- 1.4; P = 0.15). PD patients indicated that there was less impact of the dialysis treatment on their lives globally (7.25 +/- 2.12 versus 6.19 +/- 2.83; P = 0.019). In addition, PD patients noted less impact of the therapy in 14 of the 15 domains examined. With the use of a proportional odds model analysis, the only significant predictor of overall satisfaction and impact of therapy was dialysis modality (P = 0.037 and P = 0.021, respectively). Patients also were asked to comment freely on the positive and negative effects of the dialysis treatments on their lives, and a taxonomy of patient perceptions and concerns was developed. This study suggests that PD patients in general are more satisfied with their overall care and believe that their treatment has less impact on their lives than HD patients.

Changes of Coronary Calcification After Kidney Transplantation

Coronary artery calcification (CAC) in patients with end-stage renal disease is driven by uremia and increased serum calcium and phosphate levels. Improvement in calcium-phosphate homeostasis and uremia by kidney transplantation therefore might favorably influence CAC. We measured the extent of CAC by using multidetector computed tomography in 31 patients immediately after transplantation and at 6 and 12 months' follow-up. Baseline and follow-up measurements were compared, and the effect of atherogenic factors on CAC progression was determined by means of multivariate regression analysis. Mean total Agatston score increased significantly from baseline to 6 months (716 +/- 980 [SD] versus 916 +/- 1,307; P < 0.001), but remained unchanged at 12 months' follow-up (890 +/- 1,263; P = not significant). Progression of calcification was present only in patients with a baseline total Agatston score higher than 10. In these patients, the score increased from 964 +/- 1,028 to 1,234 +/- 1,385 (P < 0.001) at 6 months and remained stable thereafter (1,199 +/- 1,338; P = not significant). Duration of pretransplantation dialysis treatment and smoking were identified as independent predictors of posttransplantation CAC progression. Conversely, changes in calcium and phosphate levels were not associated with calcification. This study shows that CAC progresses during the early posttransplantation course, but slows between 6 and 12 months after transplantation. The extent of early calcification is influenced mainly by dialysis treatment duration and smoking.

Acquired cystic kidney disease and arterial hypertension in hemodialysis patients

Acquired cystic kidney disease (ACKD) and arterial hypertension (AH) are both frequent complications in hemodialysis (HD) patients. Until now, AH has not been described as a complication of ACKD. Our study included 86 HD patients (46 men and 40 women; mean age 51.3 years; mean duration of HD treatment 55.3 months). Their native kidneys were examined with an ATL-HDI 3000 ultrasound device (2-4 MHz convex probe). Depending on the number of cysts in the kidney, the manifestations were divided into three grades: grade 0: no cysts; grade 1: fewer than ten cysts in both kidneys; grade 2: more than ten cysts in both kidneys. Blood pressure was measured 30 minutes before and after HD. Mean one-month values were analyzed. AH was defined as systolic blood pressure > or = 150 mmHg, diastolic blood pressure > or = 90 mmHg and/or antihypertensive treatment. The diameter of the inferior vena cava (indicator of dry weight) was measured with the same ultrasound device as the kidneys three hours after HD. ACKD was present in 48 (55.8%) patients, there was no statistically significant difference regarding sex. Twenty-four (50%) patients had grade 1 ACKD and 24 (50%) grade 2 ACKD. Sixty-eight (79.1%) patients suffered from AH, which was significantly more common among the men (P = 0.048). AH was detected before HD in 68 (79.1%) patients and in 54 (62.8%) patients also after HD. Thirty-nine (45.3%) patients suffered simultaneously from ACKD and AH; 22 (56.4%) of them were men and 17 (43.6%) women. No significant correlation between AH and ACKD was established. The prevalence and grade of ACKD were significantly associated with the duration of dialysis treatment (P < 0.01). Multiple regression analysis detected a significant correlation only between AH and the diameter of the inferior vena cava (P < 0.05). ACKD is common in HD patients. Its prevalence and grade increase with the duration of dialysis treatment. ACKD is not associated with AH. There is a correlation between the diameter of the inferior vena cava, as a factor of circulating fluid volume, and AH in HD patients.

Polyneuropathy in hemodialysis patients: The most sensitive electrophysiological parameters and dialysis adequacy

Polyneuropathy (PNP) is a common complication in hemodialysis (HD) patients. Electrophysiological parameters are quantitative indices of its severity. The aim of our study was to find the prevalence of pathologic electrophysiological parameters, to assess their prevalence in relation to duration of HD treatment and age, to establish which parameters are the most sensitive in demonstrating PNP and to find an association between them and HD adequacy. We included 84 (50 men, 34 women) HD patients (average age 47.32 years; average dialysis duration 62.56 months) and divided them into three groups according to the duration of HD treatment. Each group was further divided into two subgroups according to age. We included electrophysiological parameters for evaluation of motor and sensory nerve functions (Medelec Sapphire Premiere device). HD adequacy was measured with urea kinetic modeling (Kt/V). PNP was found in 77 (91.6%) HD patients and was more common in men (P < 0.016). The association between the number of pathologic electrophysiological parameters and age (P < 0.0001), duration of HD treatment (P < 0.009) and HD adequacy (P < 0.0001) was statistically significant. The most sensitive electrophysiological parameter was the latency of the F wave (pathologic values of F wave latency in the lower limbs in 86% patients and in the upper limbs in 49%). Sensory conduction velocities and the amplitudes of the orthodromic sensory action potentials and the M wave were also sensitive parameters. The F wave latency of different nerves was associated with dialysis adequacy. PNP is frequent in HD patients and is associated with age and duration of dialysis treatment. The most sensitive electrophysiological parameter of PNP is F wave latency, which may also be used as a parameter of dialysis adequacy.

Cardiovascular Calcification in Patients With End‐stage Renal Disease

Vascular calcifications are very frequent extraosseous calcifications in patients with chronic renal disease. They occur in the intima and in the media. They are associated with decreased arterial elasticity and increased mortality. The risk factors are: advanced age, duration of dialysis treatment, diabetes, increased phosphate concentration, the dose of Ca-containing phosphate binders and inflammation. It is now well established that vascular smooth muscle cells actively take up phosphate to form bioapatite. This process is associated with a phenotypic transformation of vascular smooth muscle cells during which they express osteoblast markers. Lipids and inflammatory cytokines also increase bioapatite formation. Calcification inhibitors are matrix Gla protein and fetuin-A. Decreased serum fetuin-A concentration is associated with a higher mortality rate in dialysis patients. An important preventive measure for vascular calcification is the substitution of Ca-containing by non-Ca-containing phosphate binders.

Cinacalcet Hydrochloride

Oral cinacalcet hydrochloride (HCl) [Sensipar, Mimpara] is the first in a new class of therapeutic agents, the calcimimetics, and has a novel mechanism of action. It directly modulates the principal regulator of parathyroid hormone (PTH) secretion, namely the calcium-sensing receptor (CaR) on the chief cells in the parathyroid gland. Cinacalcet HCl reduces circulating PTH levels by increasing the sensitivity of the CaR to extracellular calcium. In three pivotal phase III, 26-week, randomised, double-blind, multicentre trials in chronic kidney disease (CKD) patients (n = 1136) on dialysis with uncontrolled secondary hyperparathyroidism (HPT), a significantly higher proportion of oral cinacalcet HCl 30-180 mg/day than placebo recipients achieved a reduction in intact PTH levels to < or =250 pg/mL. Cinacalcet HCl treatment also simultaneously lowered serum calcium and phosphorus, and calcium-phosphorous product levels. Notably, cinacalcet HCl proved effective in a broad range of CKD patients on dialysis with uncontrolled secondary HPT, regardless of disease severity, duration of dialysis treatment, dialysis modality, race, age, gender, or concurrent phosphate binder or vitamin D sterol use. Cinacalcet HCl (60-360 mg/day) also reduced elevated serum calcium levels by > or =1 mg/dL in 15 of 21 (71%) patients with parathyroid carcinoma in an open-label, multicentre, dose-titration trial. Cinacalcet HCl was generally well tolerated in clinical trials. Most treatment-emergent adverse events were mild to moderate in severity.

Operative Treatment of Hip Fracture in Haemodialysed Patients

To study operative treatment and postoperative clinical outcomes of hip fracture in haemodialysed patients. In 12 patients (8 men and 4 women) undergoing haemodialysis, 14 hip fractures were treated. Of these, 8 hips were treated with bipolar hip arthroplasty, one hip with total hip arthroplasty, 4 hips with a compression hip screw, and one hip with a gamma nail. The mean duration of dialysis treatment until fracture was 7 years. During a mean postoperative follow-up period of 17 months (range, 1-44 months), the patients' renal condition, type of fracture, and level of activities of daily living before and after surgery were assessed. Of the 7 patients who died during a mean follow-up period of 17 months, 2 died from myocardial infarction, 2 from sepsis, and one each from gastric cancer, pulmonary oedema, and liver failure. Five of the 8 patients with diabetic nephropathy died, whereas 6 of the 8 patients who underwent bipolar hip arthroplasty or total hip arthroplasty died. Most of the patients had declined level of activities of daily living postoperatively. For haemodialysed patients with fractures, it is essential to select the most suitable operating method and to conduct vigilant management before and after the operation.

IGF-I System Responses During 12 Weeks of Resistance Training in End-Stage Renal Disease Patients

2075 Early cross-sectional observations that circulating IGF-I was associated with fitness level suggested that chronic physical training would favor anabolic processes by increasing circulating IGF-I. However, recent studies have shown that IGF-I is actually decreased in response to short-term training. More information is required to verify this hypothesis especially across a range of healthy vs. unhealthy populations. PURPOSE: To examine the hypothesis that 12 weeks of resistance training would alter circulating concentrations of IGF-I system components in end-stage renal disease (ESRD) patients. METHODS: Ten ESRD patients (42.8 ± 4.6 yr, 172.7 ± 3.2 cm, 90.0 ± 4.9 kg, duration of dialysis treatment 41.6 ± 19.0 months) underwent 12 weeks of resistance training after a 6 week control period and had fasted morning blood samples drawn on 4 occasions (weeks −6, 0, 6, 12). Training consisted of two sessions per week of eight to nine whole body exercises, utilizing 10 to 15 repetitions per set with progressive increases in volume and resistance. Immunoassays were performed for serum total and free IGF-I, IGF binding protein (IGFBP) −2 and −3, acid labile subunit (ALS), and growth hormone binding protein (GHBP). Immunoaffinity depletion of ALS-based complexes allowed measurement of non-ternary (i.e., binary) IGF-I and IGFBP-3. RESULTS: All IGF-I measures were stable during the control period (week −6 to 0) and no changes were observed for the first 6 weeks of resistance training. At week 12, significant (p ≤ 0.05) reductions from week 0 values were demonstrated for total IGF-I (320.2 ± 43.2 vs. 267.1 ± 41.0 ng/mL), ternary IGF-I (253.7 ± 39.1 vs. 206.2 ± 36.5 ng/mL), and the IGF-I/IGFBP-3 molar ratio (2.4 ± 0.2 vs. 1.9 ± 0.3). No differences (p > 0.05) existed for free IGF-I, IGFBP-2, IGFBP-3, ALS, or GHBP. The proportion of IGF-I in ternary (∼76.3 ± 6.8%), non-ternary (∼22.5 ± 6.6%), and free (∼1.2 ± 0.5%) forms remained stable throughout the training. Significant improvements in strength (e.g., isokinetic peak torque of leg extensors) and functional performance (e.g., maximum walking speed and distance covered in 6 minute walk) were also observed. CONCLUSION: 12 weeks of resistance training in ESRD patients induced a decline in total IGF-I, but did not alter the proportion of IGF-I circulating in free, ternary or non-ternary molecular complexes. The decline in IGF-I occurred in the presence of positive training adaptations as measured by physical performance outcome variables. We conclude that the decline of circulating IGF-I during 12 weeks of training, despite being suggestive of a catabolic state, appears to be reflective of favorable neuromuscular anabolic adaptations.

IGF-I System Responses During 12 Weeks of Resistance Training in End-Stage Renal Disease Patients

2075 Early cross-sectional observations that circulating IGF-I was associated with fitness level suggested that chronic physical training would favor anabolic processes by increasing circulating IGF-I. However, recent studies have shown that IGF-I is actually decreased in response to short-term training. More information is required to verify this hypothesis especially across a range of healthy vs. unhealthy populations. PURPOSE: To examine the hypothesis that 12 weeks of resistance training would alter circulating concentrations of IGF-I system components in end-stage renal disease (ESRD) patients. METHODS: Ten ESRD patients (42.8 ± 4.6 yr, 172.7 ± 3.2 cm, 90.0 ± 4.9 kg, duration of dialysis treatment 41.6 ± 19.0 months) underwent 12 weeks of resistance training after a 6 week control period and had fasted morning blood samples drawn on 4 occasions (weeks −6, 0, 6, 12). Training consisted of two sessions per week of eight to nine whole body exercises, utilizing 10 to 15 repetitions per set with progressive increases in volume and resistance. Immunoassays were performed for serum total and free IGF-I, IGF binding protein (IGFBP) −2 and −3, acid labile subunit (ALS), and growth hormone binding protein (GHBP). Immunoaffinity depletion of ALS-based complexes allowed measurement of non-ternary (i.e., binary) IGF-I and IGFBP-3. RESULTS: All IGF-I measures were stable during the control period (week −6 to 0) and no changes were observed for the first 6 weeks of resistance training. At week 12, significant (p ≤ 0.05) reductions from week 0 values were demonstrated for total IGF-I (320.2 ± 43.2 vs. 267.1 ± 41.0 ng/mL), ternary IGF-I (253.7 ± 39.1 vs. 206.2 ± 36.5 ng/mL), and the IGF-I/IGFBP-3 molar ratio (2.4 ± 0.2 vs. 1.9 ± 0.3). No differences (p > 0.05) existed for free IGF-I, IGFBP-2, IGFBP-3, ALS, or GHBP. The proportion of IGF-I in ternary (∼76.3 ± 6.8%), non-ternary (∼22.5 ± 6.6%), and free (∼1.2 ± 0.5%) forms remained stable throughout the training. Significant improvements in strength (e.g., isokinetic peak torque of leg extensors) and functional performance (e.g., maximum walking speed and distance covered in 6 minute walk) were also observed. CONCLUSION: 12 weeks of resistance training in ESRD patients induced a decline in total IGF-I, but did not alter the proportion of IGF-I circulating in free, ternary or non-ternary molecular complexes. The decline in IGF-I occurred in the presence of positive training adaptations as measured by physical performance outcome variables. We conclude that the decline of circulating IGF-I during 12 weeks of training, despite being suggestive of a catabolic state, appears to be reflective of favorable neuromuscular anabolic adaptations.

Quality of life on chronic dialysis: comparison between haemodialysis and peritoneal dialysis

Quality of life (QOL) assessment in patients on chronic haemodialysis (HD) or peritoneal dialysis (PD) has only rarely been carried out with the generic Euroqol-5D questionnaire. All chronic HD and PD patients in the 19 centres of western Switzerland were requested to fill in the validated Euroqol-5D generic QOL questionnaire, assessing health status in five dimensions and on a visual analogue scale, allowing computation of a predicted QOL value, to be compared with the value measured on the visual analogue scale. Of the 558 questionnaires distributed to chronic HD patients, 455 were returned (response rate 82%). Fifty of 64 PD patients (78%) returned the questionnaire. The two groups were similar in age, gender and duration of dialysis treatment. Mean QOL was rated at 60+/-18% for HD and 61+/-19% for PD, for a mean predicted QOL value of 62+/-30 and 58+/-32% respectively. Results of the five dimensions were similar in both groups, except for a greater restriction in usual activities for PD patients (P = 0.007). The highest scores were recorded for self-care, with 71% HD and 74% PD patients reporting no limitation, and the lowest scores for usual activities, with 14% HD and 23% PD patients reporting severe limitation. Experiencing pain/discomfort (for HD and PD) or anxiety/depression (for PD) had the highest impact on QOL. QOL was equally diminished in HD and PD patients. The questionnaire was well accepted and performed well. Improvement could be achievable in both groups if pain/discomfort and anxiety/depression could be more effectively treated.

Death after withdrawal from dialysis: the most common cause of death in a French dialysis population.

Discontinuation of dialysis is a common cause of death in end-stage renal disease (ESRD) patients in North America and the UK, but appears to be unusual in the rest of Europe. The aim of this retrospective study was to characterize withdrawal from dialysis in a French population cohort. We assessed the cause of death, and the medical and social characteristics of chronic dialysis patients in a French population who died in 2001. We compared patients who died after withdrawal from dialysis and patients continuing dialysis until death. We determined the decision-making process when dialysis was withdrawn. In a population cohort of 1436 dialysis patients, 196 died (13.9%). Of them, 40 patients (20.4%) died following withdrawal from dialysis. This was the most common cause of death, followed by cardio-vascular disease (18.4%). Patients withdrawing from dialysis had a significantly higher rate of dementia (17.5 vs 6.4%, P = 0.02), a poor general condition (55 vs 15.4%, P < 0.001), and were dependent in their life for everyday activities in comparison with patients who died from other causes. They were not different in age, sex, duration of dialysis treatment, dialysis technique, cardio-vascular disease, diabetes, stroke or cancer, but the sample size was small. Treatment was more often removed in patients with severe medical complications and/or cachexia (90%). The decision to stop dialysis was made most often by a physician (77.5%). Death after withdrawing from dialysis was the most common cause of death in ESRD patients in our French population cohort. The patients who died after discontinuation of treatment were more often in a poor general condition, near the end of life, and most often the physician decided to stop dialysis treatment.

Analysis of the relationship between norepinephrine and asymmetric dimethyl arginine levels among patients with end-stage renal disease.

High sympathetic activity and alterations in nitric oxide synthesis attributable to accumulation of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) have recently been identified as potential causal mechanisms for the high cardiovascular mortality rates among patients with ESRD. The link between these risk factors has not been studied. Therefore, the relationship between plasma norepinephrine (NE) and ADMA levels was examined in a large cohort of hemodialysis patients (n = 224), and whether these factors interacted in predicting all-cause mortality and new cardiovascular event rates among those patients was investigated. Plasma ADMA levels were strongly associated with plasma NE levels (P < 0.001) and to a lesser extent with heart rate (P < 0.01). In multivariate analyses, the ADMA-NE correlation was observed to be independent of age, gender, serum albumin levels, arterial pressure and antihypertensive treatment, duration of dialysis treatment, diabetes mellitus, and other risk factors. NE was an independent significant predictor of both death and cardiovascular events in Cox models not including ADMA. However, when ADMA was introduced into those models, NE became a largely nonsignificant predictor of those outcomes, whereas plasma ADMA levels emerged as a highly significant predictor of both death (P < 0.001) and cardiovascular events (P < 0.001). These findings suggest that ADMA is an intervening factor in the causal pathway leading to those outcomes. Plasma NE and ADMA concentrations are strongly related among patients with ESRD. These two factors are likely to be involved in the same causal pathway leading to death and cardiovascular events among those patients.

Retinal light sensitivity in haemodialysis patients.

The aim of the present study was to compare retinal light sensitivity between normal healthy subjects and chronic renal failure patients treated with maintenance haemodialysis (HD), as well as to determine whether there is a correlation between visual field loss and the age of HD patients, duration of HD treatment and hypertensive retinopathy in HD patients. A total of 50 eyes of 25 HD patients (16 male, nine female) and 30 eyes of 15 controls underwent visual field testing on the C 30-2 program of the Humphrey field analyser. Significant reduction in retinal light sensitivity with mean deviation (MD) P values less than 5% was found in 36% (18 eyes), pattern standard deviation (PSD) P values less than 5% in 16 eyes (32%) and corrected pattern standard deviation (CPSD) P values less than 5% in 16 eyes (32%) of HD patients. In control group, all MD, PSD, and CPSD P values were within normal limits. No correlation between reduction of retinal light sensitivity and age or duration of dialysis treatment was observed in HD patients. The reduction of retinal light sensitivity was significantly greater in HD patients with hypertensive retinopathy. In 36% of eyes from our HD patients without ophthalmoscopically evident arteriolar occlusion on fundus examination, a significant reduction in retinal light sensitivity was observed. The reduction was significantly greater in HD patients with hypertensive retinopathy.

Atherosclerosis in patients with analgesic nephropathy treated with haemodialysis

SUMMARY: Accelerated atherosclerosis was reported to be associated with chronic analgesic consumption, but most studies were retrospective, and individual findings have almost never been controlled with regard to other atherosclerotic risk factors. Ten haemodialysis patients with analgesic nephropathy (group I) and 19 haemodialysis patients where renal failure was not caused by analgesic nephropathy (group II) were included in the study. All patients were female without diabetes. Using B‐mode ultrasonography, we compared intima‐media thickness (IMT) in the carotid arteries and plaque occurrence, and their thickness in group I with that in group II. the possible differences in atherosclerotic risk factors in both groups were also investigated. In group I, the average age was 60.2 years, and the average dialysis treatment was 55.7 months. In group II, the average age was 54.6 years, and the average duration of dialysis treatment was 50.4 months. We found no statistically significant difference in the age and duration of dialysis treatment between groups I and II. the IMT values of the carotid arteries (0.97 vs 0.78 mm; P= 0.027) were significantly higher in group I. More patients had plaques in group I (90 vs 57.9%), and the number of plaques (P= 0.037) and their thickness (P= 0.043) were significantly higher in this group. There was no statistically significant difference in the atherosclerotic risk factors between groups I and II. the results indicate that patients with analgesic nephropathy treated with haemodialysis showed advanced atherosclerosis compared with other haemodialysis patients, despite no difference being found in the atherosclerotic risk factors between these patients.

Response of peripheral blood mononuclear cells in hemodialyzed patients against endotoxin and muramyldipeptide

Microbial fragments of endotoxin (ET) and peptidoglycan (PG) are recognized as pyrogen in dialysate. The aim of this study was to evaluate the effect of contaminated dialysate on peripheral blood mononuclear cells (PBMC) in hemodialyzed patients by measuring production of interleukine 1-beta (IL-1beta) in vitro. Venous blood was withdrawn before dialysis session. The effects of a dialysis membrane, a magnitude of dialysate contamination and a duration of hemodialysis were studied. PBMC was stimulated by the addition of water containing either ET or muramyldipeptide (MDP), the minimum biological activated fragment of PG, or ET+MDP. IL-1beta production of PBMC stimulated by ET or ET+MDP in patients on hemodialysis using a polysulfon (PS) membrane was significantly lower than those using a cuprammonium-rayon (CU) membrane, ethylenevinylalcohol (EVAL) membrane, polymethylmetacrylate (PMMA) membrane, respectively. Among patients on the PS membranes, those who were exposed to dialysate with higher pyrogen contamination had lower PBMC cytokine production than those dialyzed with ultrapure dialysate. Response of PBMC in patients against ET+MDP stimulant decreased with duration of dialysis treatment. This suggested that chronic exposure to ET or MDP during hemodialysis treatment, might cause a tolerance against ET and ET+MDP in PBMC.

Long-term impact of renal transplantation on carotid artery properties and on ventricular hypertrophy in end-stage renal failure patients.

The aim of this study was to examine prospectively the impact of renal transplantation on the morphological and functional characteristics of the carotid arteries and heart in a group of end-stage renal failure patients without overt cardiovascular disease, followed up for >3 years. Twenty-two patients were evaluated 2-3 weeks after renal transplantation, and again 12 and 40 months post-transplant, using high resolution ultrasound imaging and echocardiography. Kidney and patient survival were 100% at the end of follow-up without any major cardiovascular events. After 40+/-1.2 months, carotid morphological parameters were normalized: carotid intima-media thickness fell from 788+/-24 to 676+/-32 microm (P<0.01) and the carotid wall/lumen ratio fell from 118+/-3 to 103+/-3 microm (P<0.01). Significant reduction of left ventricular (LV) posterior wall thickness (11.5+/-0.2 to 11.3+/-0.2 mm, P<0.05) and LV mass index (172+/-9 to 158+/-8 g/m(2), P<0.01) was already observed after 12+/-0.2 months. Further reduction of LV posterior wall thickness (10.4+/-0.3 mm, P<0.01) and of LV mass index (136+/-7 g/m(2), P<0.01) also occurred after 40+/-1.2 months. However, carotid distensibility (19.5+/-2.1 vs 22+/-2.4, not significant (NS)) and LV compliance (early to atrial flow ratio: 1.2+/-0.1 vs 1.3+/-0.1, NS) remained abnormal, and normalization of the LV mass was attained by only 25% of the patients with LV hypertrophy on baseline. Multiple stepwise regression analysis showed that the rate of change of reduction of the intima-media thickness was influenced by age (negative association, P<0.001) and was positively related to white race (P<0.05), female sex (P<0.01) and to the parallel reduction of maximum carotid diameter (P<0.001). Reduction of LV mass index over time was negatively related to the duration of dialysis treatment and to the parallel increase observed in body mass index and haematocrit, and was positively related to the simultaneous reduction of diastolic blood pressure (P<0.01 for all variables). Successful renal transplantation improves but does not cause complete regression of the cardiovascular alterations of end-stage renal disease. Only intima-media thickness was normalized by transplantation, whereas LVMI and carotid and ventricular distensibility remained abnormal. The results suggest that extended duration of dialysis, weight gain, high blood pressure and high haematocrit may adversely affect the rate of change of post-transplant cardiovascular hypertrophy.

Relationship between Salt Intake, Nitric Oxide and Asymmetric Dimethylarginine and Its Relevance to Patients with End-Stage Renal Disease

Patients with essential hypertension (n = 24) were administered a low-salt diet (2 g NaCl/day), a high-salt diet (20–23 g) and then a low-salt diet for 7 days, and plasma levels of nitrate and nitrite (NOx) and asymmetric dimethylarginine (ADMA) were examined. There was a negative correlation between the percent changes in mean blood pressure and the plasma NOx concentration after salt loading and restriction. The percent change in plasma ADMA concentration was negatively correlated with that in the plasma NOx concentration after salt loading and restriction. In patients with end-stage renal disease (n = 51), the plasma ADMA concentration was positively correlated with the duration of dialysis treatment. The frequency of cardiovascular events was greater in patients with a plasma ADMA level of ≥3 µM than in those with a plasma AMDA level of <3 µM. The results indicate that ADMA is not only a modulator of salt sensitivity in hypertension but also a cardiovascular risk factor in end-stage renal disease.

TWENTY-FOUR HOUR BLOOD PRESSURE PROFILE AND LEFT VENTRICULAR HYPERTROPHY EARLY AFTER RENAL TRANSPLANTATION

Background: Left ventricular hypertrophy is common in renal transplant patients but the factors influencing its development remain to be determined. The present investigation was conducted to study the effect of blood pressure load on the left ventricular mass of recently transplanted patients using 24-h ambulatory blood pressure monitoring (ABPM). Methods: We studied 30 renal transplant (RT) patients (36.1 ± 13.7 years old, 11 males, 26 Whites, 4 diabetics, 15 under antihypertensive medication, 21 recipients of cadaver donors, and all treated with steroids, cyclosporin and azathioprine and with adequate (serum creatinine< 1.8 mg/100 ml) renal function). The median duration of dialysis treatment before transplant was 37 months, and the studies were performed during the first 40 days post-transplantation. Blood pressure was measured after a 15-min rest (casual blood pressure) and during a 24-h period with a SpaceLabs™ apparatus. Echocardiograms were obtained from all patients. Results: Mean left ventricular mass index (LVMI) was 153 ± 44 g/m2; casual systolic and diastolic BP (mmHg) was 152 ± 25 and 92 ± 13, whereas systolic and diastolic 24-h BP was 133 ± 12 and 85 ± 8, respectively. The systolic sleeping BP/awake systolic BP (SSBP/ASBP) ratio was 0.94 ± 0.07, and 73% of the patients did not show a significant (>10%) fall of systolic blood pressure during sleep. Multivariate analysis showed that awake systolic blood pressure was the only variable that independently influenced LVMI after adjusting for confounding factors (regression coefficient = 0.49, p = 0.01). Casual systolic and diastolic BP, sleeping systolic and diastolic blood pressure, 24-h heart rate, age, race, gender, smoking, body mass index, duration of dialysis, diabetes, antihypertensive and immunosuppressive drugs and levels of hematocrit, creatinine and serum lipids did not correlate with LVMI. Conclusion: The data indicate that left ventricular hypertrophy during the early post-transplant period is mainly influenced by awake blood pressure load. They also suggest that ABPM may be more useful in the diagnosis and management of post-transplant hypertension than casual BP. The findings emphasize the importance of rigid blood pressure control in renal transplant recipients.

Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric-oxide synthase, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. We investigated the relation between cardiovascular risk factors and plasma ADMA concentration in a cohort of haemodialysis patients (n=225), and tested the predictive power of ADMA for mortality and cardiovascular outcomes. Patients had standard dialysis three times a week. We accurately recorded cardiovascular events over a mean follow-up of 33.4 months (SD 14.6); these events were reviewed by a panel of physicians. We identified correlates of plasma ADMA by univariate and multivariate analyses. On univariate analysis, ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration, and was inversely related to serum albumin concentration. On multivariate analysis, only plasma fibrinogen (p=0.0001) and serum albumin (p=0.04) concentrations were independently related to plasma ADMA concentration (multiple r=0.44, p=0.0001). 83 patients died, 53 (64%) by cardiovascular causes. In a Cox's proportional-hazards model, plasma ADMA ranked as the second factor predicting overall mortality (hazard ratio 1.26, 95% Cl 1.11-1.41, p=0.0001) and cardiovascular events (1.17, 1.04-1.33, p=0.008). In haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure.