Uraemic symptoms, nutritional status and renal function in pre-dialysis end-stage renal failure patients.

BACKGROUND: Deciding on the right moment to initiate dialysis and finding the best method to establish this critical stage of chronic renal failure are both controversial issues. This study attempted to address this subject by correlating a uraemic score with the most common clinical methods for assessing renal function in pre-dialysis chronic renal failure (end-stage renal disease, ESRD) patients. METHODS: The study group consisted of 201 non-selected ESRD patients. A uraemic score, composed of the uraemic symptoms, the subjective global assessment of nutritional status, serum albumin concentration, and protein catabolic rate normalized for ideal body weight, was taken as a clinical marker of uraemic toxicity. Correlations that best fit this uraemic score with creatinine clearance (Ccr), the arithmetic mean of Ccr, urea clearance (Ccr-Cu) and Kt/V urea were then investigated. RESULTS: Thirty-six per cent of patients had malnutrition. By multiple logistic regression analysis, the presence of comorbidity, Ccr-Cu and haematocrit were the best determinants of malnutrition. The correlation that best fit Ccr or Ccr-Cu with the uraemic score was a cubic curve (r=0.38, P<0.0001, and r=0.42, P<0.0001, respectively), in which an ascending inflection was observed when Ccr and Ccr-Cu fell below 12-13 and 10 ml/min, respectively. However, the relationship between Kt/V urea and the uraemic score was less predictable, especially in male patients. CONCLUSION: Ccr or Ccr-Cu are reliable methods for establishing the degree of severity of chronic renal failure below which the development of symptoms and malnutrition are highly prevalent. In contrast, Kt/V urea may be a less sensitive and specific method for assessing the severity of uraemia in ESRD patients.     

Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients.

BACKGROUND: Experimentally, leptin has a positive effect on bone mass when infused intravenously, but a negative one after intracerebroventricular administration. Renal failure increases its serum level above the concentration beyond which its transport to the brain may be saturated. Thus, we tested, in a chronic haemodialysis population, the hypothesis of a positive relationship between serum leptin and bone mineral density (BMD) when serum levels are above this threshold. METHODS: Serum leptin (using a two-site RIA), and BMD at the femoral neck, midshaft, and ultradistal radius, as measured by DEXA, were assessed in 17 female and 16 male chronic dialysis patients, with comparable calcium and phosphate metabolism, age and dialysis duration. RESULTS: Polynomial regression analysis showed a U-shaped correlation between BMD Z-score, with an inflexion point, which may correspond to the concentration threshold at which leptin blood-brain carrier is saturated. Linear regression analysis showed no correlation between BMD and serum leptin levels below these points but a significant positive correlation between BMD at the two radius sites and leptin levels above these points. The correlation remained significant after adjustment for BMI, serum PTH and duration of dialysis. Leptin levels were twice as high in female patients and associated with higher BMD Z-scores close to zero. CONCLUSIONS: This study suggests a bone-sparing effect of serum leptin in haemodialysis patients only when the serum levels of leptin were higher than the presumed threshold of blood-brain transport saturation. Higher leptin levels in post-menopausal female haemodialysis patients than in male patients may account for their slower bone loss with ageing.     

Leptin concentrations in semen are correlated with serum leptin and elevated in hypergonadotrophic hypogonadism

Leptin seems to play a role in both food intake and energy balance as well as in the regulation of reproductive features. In order to investigate the regulation of testicular functions by leptin we analysed leptin concentrations in the semen of men with different andrological diseases. It was demonstrated that semen leptin concentrations were inversely correlated with serum testosterone levels and directly with serum leptin concentrations. Furthermore, semen leptin concentrations display only a fraction of serum leptin levels. Semen leptin levels of patients with azoospermia due to hypergonadotrophic hypogonadism, associated with increased follicle-stimulating hormone levels and of high-grade oligozoospermia, were significantly elevated (1.19 +/- 0.46 and 1.09 +/- 0.54 microg l(-1), respectively), while semen levels of leptin in patients with obstructive azoospermia (0.54 +/- 0.41 microg l(-1)) and low-grade oligozoospermia (0.54 +/- 0.34 microg ml(-1)) were comparable with those of normozoospermic men (0.21 +/- 0.21 microg l(-1)). Our data suggest that dysfunction of testicular epithelia as found in hypergonadotrophic hypogonadism and high-grade oligozoospermia with decreased testosterone levels causes elevated spermal leptin concentrations. However, the correlation of semen with serum leptin concentrations indicates that leptin is not actively transported but rather leaks through the blood-testis barrier.     

Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients.

BACKGROUND: The accumulation of advanced glycation end-products (AGEs) in end-stage renal disease (ESRD) influenced by dialysis modalities is of current interest. Highly permeable membranes in haemodialysis or haemofiltration should be able to eliminate circulating AGEs as well as their AGE precursors more efficiently. METHODS: In our study, 10 non-diabetic and 10 diabetic ESRD patients were on haemodialysis with low-flux membranes (LF) followed by a cross-over haemodialysis with high-flux or super-flux polysulfone membranes (HF, SF) for 6 months each. We measured the protein-bound pentosidine and free pentosidine serum levels by high-performance liquid chromatography (HPLC) as well as the serum AGE peptide, AGE-beta(2)-microglobulin and beta(2)-microglobulin concentrations, using ELISA assays. RESULTS: All parameters investigated were significantly higher in dialysis patients than in healthy subjects. The reduction rates during a single dialysis session were found to be higher using the SF than those obtained with the HF (free pentosidine 82.4+/-7.3 vs 76.6+/- 8.7%; AGE peptides 79.7+/-7.7 vs 62.3+/-14.7%; AGE-beta(2)-microglobulin 64.0+/-16.5 vs 45.4+/-17.7%; beta(2)-microglobulin 70.5+/-5.6 vs 58.2+/-6.0%). The protein-bound pentosidine levels remained constant over the respective dialysis sessions. In the 6-month treatment period with the SF, decreased pre-dialysis serum levels of protein-bound pentosidine, free pentosidine and AGE peptides were observed in non-diabetics and diabetics as compared with values obtained with the LF. The respective pre-dialysis AGE-beta(2)-microglobulin concentrations decreased insignificantly, whereas those of beta(2)-microglobulin were significantly lower. Using the HF dialyser, only moderate changes of the parameters measured were noted. CONCLUSION: Treatment with the biocompatible polysulfone SF dialyser seems to be better suited to lower serum AGE levels and to eliminate their precursors.     

Adiponectin, leptin and thyroid hormones in patients with chronic renal failure and on renal replacement therapy: are they related?

BACKGROUND: Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients. METHODS: The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay. RESULTS: Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI. CONCLUSIONS: We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.     

Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

BACKGROUND: Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. METHODS: We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. RESULTS: Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. CONCLUSIONS: ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.     

Apolipoprotein A-IV serum concentrations are elevated in patients with mild and moderate renal failure.

Cell culture studies and investigations in mice that overexpress either human or mouse apolipoprotein A-IV (apoA-IV) revealed anti-atherogenic properties of apoA-IV. An association between low apoA-IV concentrations and coronary artery disease in humans was demonstrated; therefore, apoA-IV may also play an antiatherogenic role in humans. Because apoA-IV is markedly elevated in dialysis patients, patients with the earliest and modest stages of renal impairment were studied to assess the association of apoA-IV with GFR and atherosclerotic complications. GFR was measured by the use of iohexol in 227 non-nephrotic patients with different degrees of renal impairment. ApoA-IV increased significantly with decreasing GFR and was already elevated in earliest stages of renal disease (GFR > 90 ml/min per 1.73 m2). Multiple linear regression analysis identified renal function parameters (GFR, creatinine, and urea) as the most important determinants of apoA-IV levels in serum of these patients. Twenty-six patients had already experienced 36 atherosclerotic events. Logistic regression analysis identified three variables associated with atherosclerotic complications: age, apoA-IV, and gender. Each 1 mg/dl increase of apoA-IV decreased the odds ratio for an atherosclerotic complication by 8% (P = 0.011). The data clearly show that the anti-atherogenic apoA-IV starts to increase during the earliest phases of renal insufficiency, which makes apoA-IV an early marker of renal impairment.     

Removal of clodronate by haemodialysis in end-stage renal disease patients

BACKGROUND: Clodronate is a potent calcium-lowering drug. The effect ofhaemodialysis on clodronate pharm-acokinetics is unknown. METHODS: The removal of clodronate by haemodialysis was determined in10 end-stage renal disease patients (ESRD). A 2-h infusion of300 mg of clodronate was followed immediately by a 4-h haemodialysis.Vascular access was by AV fistula. A 1.5-m² cuprophane hollow-fibredialyser was applied. Blood flow was 205±15ml/min, dialysateflow 523±29 ml/min. Clodronate was determined by high-performanceliquid chromatography in total collected dialysate, and in bloodbefore and after the dialyser at initiation, 2 h, and 4 h ofHD. RESULTS: The initial predialyser serum concentration of clodronate was13.6 ± 4 ug/ml. It decreased to 4.9 ± 0.5 ug/mland 2.6 ± 0.5 ug/ml at 2h and 4h respectively. The clearanceof clodronate (86 ± 10 ml/min) remained unchanged duringHD. Clodronate in total collected dialysate per single 4-h HDwas 105 ± 16 mg (35% of injected dose). CONCLUSIONS: We conclude that clodronate is effectively removed from plasmaby HD. The present data together with information provided byprevious studies suggest that 300 mg of clodronate given asan 2-h infusion immediately prior to haemodialysis is an adequatedosage for ESRD patients.     

Sonographic evaluation of gallbladder motility in patients with end-stage renal disease on haemodialysis.

Thirty nine patients with end-stage renal disease on haemodialysis therapy with upper gastrointestinal symptoms were investigated for gallbladder motor function as the cause of their symptoms using cholecystosonography in fasting state, after a cholecystokinetic agent (BILOPTIN fatty meal) and after a smooth muscle relaxant (BUSCOPAN). Forty healthy individuals served as a control group. No significant difference was found between dialysis patients and healthy controls regarding the gallbladder area during fasting state, or the variation in the area of gallbladder during maximal contraction and dilatation. However, the patients on dialysis therapy of longer duration had stronger gallbladder contraction in response to a cholecystokinetic agent. Serum gastrin concentrations were increased in haemodialysis patients, but there was no consistent relationship between serum gastrin and gallbladder motility. The upper gastrointestinal symptoms of dialysis patients are unlikely to be due to disturbed gallbladder motility.     

Retrospective analysis of cisapride-induced QT changes in end-stage renal disease patients.

BACKGROUND: This study involves a retrospective in-patient chart review of end-stage renal disease (ESRD) patients receiving haemodialysis to observe if cisapride significantly increases heart rate (HR), QT, and corrected QT (QTc) intervals on 12-lead electrocardiograms (ECGs). METHODS: Medical records for 23 patients who were being treated with chronic maintenance haemodialysis and had >/=2 ECGs while on cisapride and >/=2 ECGs while off cisapride were obtained and reviewed. HR, QT, and QTc on all 12-lead ECGs, reason for admission, and past medical history were analysed. RESULTS: A total of 529 ECGs (279 on/250 off cisapride) for 23 patients were included. The results, as calculated by each patient's individual averages (n=23), on vs off cisapride respectively, were HR, 88+/-14 vs 84+/-17 beats/min (P:=0.18); QT, 373+/-39 vs 382+/-45 ms (P:=0.24); and QTc, 443+/-27 vs 441+/-21 ms (P:=0.39). No significant difference was found in the number of admissions per month while on or off cisapride. No patient had an average QTc on or off cisapride that was >500 ms. One patient died from ventricular arrhythmia 12 days after discontinuing cisapride. The patient's QTc was significantly longer on vs off cisapride (487 vs 462 ms, P:=0. 007); however, this patient had an extensive cardiac history and multiple syncopal episodes prior to the use of cisapride. CONCLUSIONS: This study found no significant overall difference in HR, QT, and QTc interval or admissions/month on vs off cisapride in ESRD patients receiving haemodialysis.     

Unilateral renal cell carcinoma with coexistent renal disease: a rare cause of end-stage renal disease.

BACKGROUND: Renal cell carcinoma (RCC) is a disorder encompassing a wide spectrum of pathological renal lesions. Coexistence of unilateral RCC and associated pathology in the contralateral kidney is an unusual and challenging therapeutic dilemma that can result in renal failure. So far, data on unilateral RCC with chronic renal failure necessitating renal replacement therapy have not been published. The aim of the present study was to evaluate the incidence of end-stage renal disease (ESRD) from unilateral RCC, and to assess the associated pathology and possible pathogenic factors. METHODS: In 1999, a survey of the 350 patients treated by chronic dialysis in Asturias, Spain, was carried out to identify and collect clinical information on patients with primary unilateral RCC whilst on their renal replacement programme. RESULTS: Seven patients were identified as having ESRD and unilateral RCC, giving an incidence of 2% of patients treated by dialysis. There was a wide spectrum of associated disease and clinical presentation. All patients underwent radical or partial nephrectomy and were free of recurrence 6--64 months after surgery. Six patients were alive and free of malignancy recurrence for 6--30 months after the onset of haemodialysis. CONCLUSION: ESRD is rare in association with unilateral RCC, but does contribute to significant morbidity. However, the data presented here are encouraging and suggest that cancer-free survival with renal replacement therapy can be achieved in such patients.     

Effect of calcium-channel blockers on calcium--phosphate metabolism in patients with end-stage renal disease

BACKGROUND: After EDTA-induced hypocalcaemia, healthy volunteers treatedwith diltiazem display more severe hyperparathyroidism thansubjects on felodipine studied under identical conditions. Thereforepatients with end-stage renal disease (ESRD) and severe secondaryhyperparathyroidism might be particularly sensitive to thisside-effect. METHODS: To test this hypothesis, seven patients with ESRD on chronichaemodialysis (3 women and 4 men) with serum levels of intactPTH ranging from 204 to 675 pg/ml were studied both before andduring the first 180 min of haemodialysis against a dialysatewith low calcium concentration (0.75 mmol/1, n=6 and 1 mmol/1,n=1) under the following three experimental conditions: control,felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). RESULTS: At onset of dialysis, plasma phosphorus level was higher ondiltiazem (2.03±0.08 mM) than on felodipine (1.64±0.10,P<0.02), and on the latter it was lower than in control condition(1.88±0.16, P<0.02). As a probable consequence, bloodionized calcium concentration was lower on diltiazem (1.14 mM±0.02,mean±SEM) than on felodipine (1.2±0.03, P<0.05)or in control condition (1.17±0.01, NS). There was atrend for intact PTH to be higher on diltiazem (324±47pg/ml) than on felodipine (246±55) or in control condition(305±49) and 1,25-dihydroxyvitamin D was higher indeedon diltiazem (6.70±0.92 pg/ml) than on felodipine (4.75±0.91,P<0.02) or control (3.87±0.62, P<0.05). Area underthe curve PTH over the first 60 min of dialysis was higher by16±7% on diltiazem than on felodipine (P<0.05). CONCLUSIONS: While on diltiazem rather than on felodipine, patients withESRD display higher plasma phosphorus levels, and slightly aggravatethe degree of severity of hyperparathyroidism recorded duringhaemodialysis against low-calcium dialysate. The longterm effectof this new observation remains to be evaluated.     

Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.

BACKGROUND: Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. METHODS: Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. RESULTS: Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. CONCLUSIONS: Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.     

Effect of haemodialysis on serum levels of tumour markers in patients with end-stage renal failure

SUMMARY: We studied the effect of haemodialysis on the serum levels of tumour markers in 78 patients, 49 men and 29 women with a mean age of 61 ± 2 years, who had been undergoing haemodialysis for 39 ± 10 months. No patient had any clinical evidence of malignancy. Serum values of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous-cell-carcinoma-related antigen (SCC), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), CA 15-3, CA 19–9, and among males prostate-specific antigen (PSA) were determined before and after dialysis. Postdialysis values, after being corrected for haemoconcentration, were compared with predialysis values. A significant increase of 32% was observed in NSE levels ( P <0.001) and of 21% in CA 15-3 ( P <0.001) after haemodialysis. A lesser, but still statistically significant, increase (8-12%) was observed in SCC, AFP and CEA levels ( P <0.05), while the values of the remaining three markers remained unchanged. In conclusion, an increase in some tumour markers was found in our patients after dialysis, a finding which requires further investigation.     

Arterial stiffening and vascular calcifications in end-stage renal disease.

BACKGROUND: Epidemiological studies have identified aortic stiffness as an independent predictor of cardiovascular mortality in end-stage renal disease (ESRD) patients. In these patients, aortic pulse wave velocity (PWV) was associated with mediacalcosis, but the influence of arterial calcifications on the viscoelastic properties of large arteries was not well characterized. The purpose of the present study was to analyse the influence of arterial calcifications on arterial stiffness in stable haemodialysed patients. METHODS: We studied 120 stable ESRD patients on haemodialysis. All patients underwent B-mode ultrasonography of common carotid artery (CCA), aorta, and femoral arteries to determine CCA distensibility, the elastic incremental modulus (Einc), and the presence of vascular calcifications. All patients underwent measurement of aortic PWV and echocardiogram. The presence of calcifications was analysed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. RESULTS: Our observations indicate that arterial and aortic stiffness is significantly influenced by the presence and extent of arterial calcifications. The extent of arterial calcifications is in part responsible for increased left ventricular afterload, and is inversely correlated with stroke volume. The influence of calcifications is independent of the role of ageing and blood pressure. Arterial calcifications density increases with age, duration of haemodialysis, the fibrinogen level, and the prescribed dose of calcium-based phosphate binders. CONCLUSIONS: The results of this study showed that the presence of vascular calcifications in ESRD patients was associated with increased stiffness of large capacity, elastic-type arteries, like the aorta and CCA. The extent of arterial calcifications increased with the use of calcium-based phosphate-binders.     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure.

BACKGROUND: Congestive heart failure (CHF) is an independent risk factor for mortality in the end-stage renal disease (ESRD) population. Nocturnal haemodialysis (NHD), a novel mode of renal replacement therapy, may be more effective than conventional haemodialysis in reducing intravascular volume or in removing uraemic toxins with vasoconstrictor or myocardial depressant actions, and may, therefore, improve the left ventricular (LV) systolic function of patients with coexisting cardiac and renal failure. METHODS: To test this hypothesis, we determined, in six patients (mean age+/-SD: 49.5+/-9 years), blood pressure (BP), ejection fraction (EF: radionucleotide angiography), left ventricular mass index (LVMI: echocardiography), LV fractional shortening (FS), and extracellular fluid volume (ECFV: bioelectrical impedance): before and after a mean of 3.2+/-2.1 years following conversion from conventional dialysis (3 days/week x 4 h) to NHD (6 nights/week x 8-10 h). RESULTS: There were significant reductions in systolic and mean arterial BP (138+/-10 to 120+/-9 mmHg, P=0.04; 99+/-6 to 86+/-7 mmHg, P=0.01). There was a significant increase in EF (28+/-12 to 41+/-18%, P=0.01) and a trend to greater LV FS (20+/-10 to 38+/-17%, P=0.06). Post-dialysis ECFV was not affected by dialysis mode (18.5+/-5.1 vs 18.2+/-3.5 l, P=0.76). The number of prescribed cardiovascular medications was reduced (2.2-0.7, P=0.02). CONCLUSIONS: In ESRD patients with systolic dysfunction, NHD leads to a sustained increase of EF and a reduction in the requirement for vasoactive medications in the absence of any reduction in post-dialysis ECFV.     

Prognostic value of heart rate variability in patients with end-stage renal disease on chronic haemodialysis.

BACKGROUND: Although decreased heart rate variability (HRV) is an independent predictor of death in various populations, its prognostic value in patients with end-stage renal disease on chronic haemodialysis is unknown. METHODS: We prospectively studied 120 chronic haemodialysis patients (age 61+/-11 years; males 51%; diabetics 38%; duration of haemodialysis therapy 50+/-114 months) who underwent 24 h electrocardiography at baseline for analysis of time- and frequency-domain HRV. RESULTS: All HRV measures in the patients were significantly reduced compared with those obtained from 62 age-matched healthy subjects. During a follow-up period of 26+/-10 months, 21 patients died (17.5%); 10 from cardiac causes and 11 from non-cardiac causes (seven fatal strokes and four other causes). A Cox proportional hazards model revealed that, of the HRV measures, decreases in the triangular index (TI), very-low-frequency (0.0033-0.04 Hz) power, ultra-low-frequency (<0.0033 Hz) power (ULF) and the ratio of low-frequency (0.04-0.15 Hz) power to high-frequency (0.15-0.4 Hz) power had significant predictive value for cardiac death. None of the HRV measures, however, had predictive value for non-cardiac death, including stroke death. Even after adjustment for other univariate predictors including age, diabetes, serum albumin and coronary artery disease, the predictive value of decreased TI and ULF remained significant-adjusted relative risk (95% confidence interval) per 1 SD decrement of TI and ULF, 3.28 (1.08-9.95) and 1.92 (1.01-3.67), respectively. CONCLUSIONS: Decreases in some HRV measures, particularly those reflecting long-term variability, are independent predictors of cardiac death in chronic haemodialysis patients.