Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure

There is a trend to start dialysis earlier in patients with chronic renal failure. Studies that suggest improved survival from earlier initiation of dialysis are flawed in that they have measured survival from start of dialysis rather than from a time point before dialysis, when patients have the same renal function. This flaw is termed lead-time bias. Using the electronic patient record at the renal unit of Glasgow Royal Infirmary, all patients were identified who had received dialysis for chronic renal failure and who had sufficient data to calculate the time point at which they reached an estimated creatinine clearance (eC(Cr)) of 20 ml/min (n = 275). This date was used to time survival. The patients were divided into early and late start groups by the median eC(Cr) for all patients at initiation of dialysis, which was 8.3 ml/min. There was no significant benefit in patient survival from earlier initiation of dialysis. A Cox proportional hazards model demonstrated a significant inverse relationship between eC(Cr) at start of dialysis and survival (hazard ratio, 1.1; P = 0.02), i.e., patients who started dialysis with a lower eC(Cr) tended to survive longer. This relationship retained significance when gender, age, weight, presence of diabetes, mode of first dialysis, initial dialysis access, hemoglobin, serum albumin, blood leukocyte count, Wright/Khan index, and eC(Cr) at the start of dialysis were taken into account. This study fails to support a policy of earlier initiation of dialysis for patients with end-stage renal failure.     

Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure

Sir, We write to express our concern about a letter recently publishedin NDT by Van Biesen et al. [1]. In this letter regarding initiationof dialysis, attention was drawn to our recent paper on thissubject [2]. In our study, we concluded that starting dialysisfor end-stage renal failure based on patients’ symptomsrather than level of renal function did not disadvantage thesepatients in terms of survival. Van Biesen et al. made two specific     

Prognosis of bedridden patients with end-stage renal failure after starting hemodialysis

Background The mean age of starting hemodialysis (HD) in patients with end-stage renal failure is gradually increasing in Japan. It is not uncommon for HD to be commenced in bedridden elderly patients who cannot give informed consent, because of brain damage. However, we have not been able to provide useful advice to their families because there was no relevant information available about the prognosis of bedridden patients on HD. Therefore, we examined the prognosis of bedridden HD patients. Methods Two hundred and nineteen patients who received HD were enrolled. These subjects were divided into five groups; (aged <50, 50–59, 60–69, 70–79, and ≥80 years at the commencement of HD), and we compared the overall prognosis between bedridden and nonbedridden patients, as well as that for each age group. Results There were 76 bedridden patients among the 219 HD patients, and the main cause of their bedridden state before starting HD was cerebrovascular disease. The 50% survival time after the start of HD was 120 months for the nonbedridden patients versus 56 months for bedridden patients. However, the mean (±SD) age of the bedridden patients was higher than that of nonbedridden patients (70 ± 13 versus 64 ± 14 years). In patients under age 50 years at the start of dialysis, the survival rate was lower in the bedridden than in the nonbedridden patients, but there were no differences between survival rates for bedridden and nonbedridden patients in the other four age groups. Conclusions The prognosis of HD patients is poor compared with the general life expectancy of the Japanese population, but whether these patients are bedridden or not has little influence on their survival.     

QT dispersion in patients with end-stage renal failure and during hemodialysis.

Interlead variability of the QT interval in surface electrocardiogram (ECG), i.e., QT dispersion, reflects regional differences in ventricular recovery time, and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT and corrected QT (QTc) interval and dispersion in chronic hemodialyzed patients. Data of 34 nondiabetic patients (male/female = 21/13; mean age, 54 +/- 15 yr) on chronic hemodialysis were studied. Polysulfone capillaries and bicarbonate dialysate containing (in mEq/L) 135 Na+, 2.0 K+, 1.5 Ca2+, and 1.0 Mg2+ were used. Simultaneous 12-lead ECG were recorded before and after hemodialysis in a standard setting. The QT intervals for each lead were measured manually on enlarged (x3) ECG by one observer using calipers. Each QT interval was corrected for patient heart rate: QTc = QT/square root of RR (in milliseconds [ms]). The average cycle intervals were 853 +/- 152 ms predialysis and 830 +/- 173 ms postdialysis; the difference was not significant. The maximal QT interval changed significantly from 449 +/- 43 to 469 +/- 41 ms (P < 0.01). The corrected maximal QT interval increased significantly from 482 +/- 42 to 519 +/- 33 ms (P < 0.01). The QT dispersion changed from 56 +/- 15 to 85 +/- 12 ms (P < 0.001) and the corrected QT interval dispersion from 62 +/- 18 to 95 +/- 17 ms (P < 0.001). During hemodialysis, the serum potassium and phosphate levels decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (mM) and from 2.3 +/- 0.5 to 1.6 +/- 0.4 (mM), respectively, whereas calcium increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (mM). It is concluded that hemodialysis increases the QT and QTc interval and QT and QTc dispersion in patients with end-stage renal failure. Thus, it may be stated that the nonhomogeneity of regional ventricular repolarization increases during hemodialysis. Measurement of QT and QTc dispersion is a simple bedside method that can be used for analyzing ventricular repolarization during hemodialysis.     

Loss of captopril-bound Fe by end-stage renal failure patients during hemodialysis

BACKGROUND: Patients on chronic hemodialysis often suffer from severe anemia, the outcome of iron deficiency and inadequate response to erythropoietin. Antihypertensive treatment with captopril worsens anemia, erythropoietin production and iron balance in hemodialysis patients. We investigated the possibility that iron chelation by captopril in the blood may result in elimination of iron-captopril complexes during hemodialysis, thus minimizing the effect of both medications. METHODS: Twelve hypertensive hemodialysis patients (group 1) were treated with 12.5 mg/day captopril, while their 12 counterparts received 1.25 mg/day ramipril. Following two weeks of treatment and two weeks of "washout", captopril in group 1 was substituted with ramipril and ramipril in group 2 was replaced by captopril for an additional two week period. Blood and dialysate samples were procured at the beginning and the end of the dialysis, for iron, aluminum, transferin, ferritin, hemoglobin (Hb) and hematocrit (Htc) determination. RESULTS: Iron, ferritin, transferin, Hb and Htc were decreased in the captopril-treated group 1. They similarly decreased in group 2 following replacement of ramipril by captopril for an additional period of two weeks. Significant amounts of iron were detected in dialysates of captopril, but not ramipril-treated patients. At the end of the dialysis, iron content was further increased in dialysates of the captopril-treated groups. CONCLUSIONS: 1) Captopril-chelated iron is eliminated in dialysis fluid during the dialysis session, apparently contributing to captopril-related anemia in patients on chronic hemodialysis. 2) Antihypertensive treatment with angiotensin converting enzyme (ACE) inhibitors other than captopril might prove advantageous for this patient category.     

Increased intracellular reactive oxygen species in patients with end-stage renal failure: effect of hemodialysis

BACKGROUND: Reactive oxygen species (ROS) have been implicated in various forms of cellular injury. ROS may cause cell damage and are involved in the pathophysiology of several diseases, including atherosclerosis and chronic inflammation. METHODS: Disturbances of intracellular ROS levels were investigated in 28 patients with end-stage renal failure. The intracellular ROS levels were measured in lymphocytes before and after hemodialysis using biocompatible membranes and were compared with those from 11 patients with end-stage renal failure, not yet on renal replacement therapy, and 27 healthy control subjects. ROS levels were measured spectrophotometrically using the intracellular dye dichlorofluorescin diacetate. RESULTS: The spontaneous production of ROS was significantly higher in lymphocytes from patients with end-stage renal failure compared with healthy control subjects (P < 0.01). The addition of 100 nmol/L phorbol-myristate-acetate (PMA) produced a significant increase of ROS, both in lymphocytes from patients with end-stage renal failure and healthy control subjects. The PMA-induced ROS increase was significantly higher in lymphocytes from patients with end-stage renal failure compared with healthy control subjects (P < 0.01). In patients with end-stage renal failure, not yet on renal replacement therapy, the PMA-induced ROS was also significantly higher compared with healthy control subjects. The PMA-induced ROS increases were significantly inhibited by catalase, but not by superoxide dismutase or the superoxide dismutase mimetic, tempol. PMA-induced ROS was significantly reduced by tyrphostin A51 in lymphocytes from patients with end-stage renal failure and from healthy control subjects (each P < 0.01), indicating the involvement of a tyrosine kinase-dependent pathway. In patients with end-stage renal failure, the spontaneous and the PMA-induced production of ROS was not significantly different before and after hemodialysis. CONCLUSIONS: Regular hemodialysis sessions using biocompatible membranes have no effect on the elevated intracellular ROS in patients with end-stage renal failure.     

Depression in end-stage renal disease hemodialysis patients

Depression has been identified as a complicating comorbid diagnosis in a variety of medical conditions, including end-stage renal disease (ESRD). Despite this, the psychological health of hemodialysis patients is understudied. The purpose of this paper is to review the research and issues involved in the assessment of depression and its sequelae in ESRD. Accurate estimation of the prevalence of depression in the ESRD population has been difficult due to the use of different definitions of depression and varied assessment techniques, the overlap of depressive symptomatology with symptoms of uremia, and the confounding effects of medications. We suggest that depressive affect is a more important construct to study than diagnosis of depression syndromes per se in patients with chronic kidney disease. The Beck Depression Inventory is a reasonable measure of depressive affect in the ESRD population, if a higher than usual cutoff score is used or if its somatic components are omitted. Several pathways link depression and ESRD, and are probably bidirectional. As such, treatment of depressive affect could impact medical as well as psychological outcomes. The need for treatment intervention trials is great. Limited evidence regarding the safety and efficacy of treatment of hemodialysis patients with selective serotonin reuptake inhibitors is available, and cognitive behavioral therapy holds promise as an intervention for depression in this complex medical population.     

Survival advantage of hemodialysis relative to peritoneal dialysis in patients with end-stage renal disease and congestive heart failure

Peritoneal dialysis (PD) has been proposed as a therapeutic option for patients with end-stage renal disease and associated congestive heart failure (CHF). Here, we compare mortality risks in these patients by dialysis modality by including all patients who started planned chronic dialysis with associated congestive heart failure and were prospectively enrolled in the French REIN Registry. Survival was compared between 933 PD and 3468 hemodialysis (HD) patients using a Kaplan-Meier model, Cox regression, and propensity score analysis. The patients were followed from their first dialysis session and stratified by modality at day 90 or last modality if death occurred prior. There was a significant difference in the median survival time of 20.4 months in the PD group and 36.7 months in the HD group (hazard ratio, 1.55). After correction for confounders, the adjusted hazard ratio for death in PD compared to the HD patients remained significant at 1.48. Subgroup analyses showed that the results were not changed with regard to the New York Heart Association stage, age strata, or estimated glomerular filtration rate strata at first renal replacement therapy. The use of propensity score did not change results (adjusted hazard ratio, 1.55). Thus, mortality risk was higher with PD than with HD among incident patients with end-stage renal disease and congestive heart failure. These results may help guide clinical decisions and also highlight the need for randomized clinical trials.     

Postoperative rhabdomyolysis in patients with end-stage renal failure

Four patients with end-stage renal failure on intermittent hemodialysis in whom rhabdomyolysis developed after major surgery are described. This possibly underdiagnosed complication was manifested by extreme hyperphosphatemia, hypocalcemia, and elevated creatine phosphokinase levels. Serum myoglobin levels further supported the diagnosis. The metabolic abnormalities reached a peak on the fourth postoperative day. The possible precipitating factors included opiates used for anesthesia and postoperative pain control, anesthetic agents, and surgical position. The preferred treatment option is increasing dialysis to control hyperphosphatemia and hypocalcemia.     

FGF-23 in patients with end-stage renal disease on hemodialysis

BACKGROUND: Fibroblast growth factor (FGF)-23 is a recently identified circulating factor which causes renal phosphate wasting disorders. Although the mechanism of regulation of FGF-23 secretion is unknown, plasma FGF-23 level may be regulated or affected by serum phosphate levels because of its hypophosphatemic effect. METHODS: We tested the hypothesis that plasma FGF-23 levels may be increased in hyperphosphatemia in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. We measured plasma FGF-23 levels in 158 male uremic patients on maintenance hemodialysis. Plasma samples were obtained before starting dialysis sessions to determine FGF-23 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma FGF-23 level exhibited significant and positive correlations with inorganic phosphate, intact parathyroid hormone (PTH), corrected calcium, and duration of hemodialysis on simple regression analyses. All these associations remained significant in multiple regression analyses. CONCLUSION: Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis. Our results may provide new insights into the pathophysiologic effects of FGF-23 on calcium-phosphate homeostasis.     

Relationship of hemodialysis access to finger gangrene in patients with end-stage renal disease

OBJECTIVE: We report a comprehensive review of our patients on hemodialysis with end-stage renal disease (ESRD) with finger gangrene to determine etiology, natural history, and prognosis of this condition. METHODS: Patients with ESRD with finger gangrene were identified from our computerized vascular registry. Presence of an ipsilateral arteriovenous fistula was determined, and patients were compared with a group of patients with ESRD without finger gangrene. Management consisted of arteriography, selective arteriovenous fistula management, and finger amputation. A multivariate analysis to determine risk factors associated with finger gangrene was performed. Repeat finger amputation and survival rates were determined with life-table analysis. RESULTS: Twenty-three patients (mean age at start of dialysis, 53 years) with finger gangrene were identified, with 48% (n = 11) having a functional ipsilateral arteriovenous fistula. Arteriography was consistent with diffuse atherosclerosis involving the radial, ulnar, palmar, and digital arteries precluding attempts at distal arterial bypass. Repeat finger amputations were necessitated in 52% of patients (n = 12), and bilateral finger gangrene developed in 61% of patients (n = 14). Starting dialysis at age less than 55 years (P =.0004), diabetes (P =.001), coronary artery disease (P =.0212), and lower extremity arterial occlusive disease (P <.0001) were significantly associated with finger gangrene. CONCLUSION: The young diabetic patient with diffuse vascular disease and ESRD is at high risk for the development of finger gangrene on chronic hemodialysis. Finger gangrene is the result of distal atherosclerosis and is not primarily related to dialysis access.     

终末期肾脏病血液透析患者不安腿综合征

不安腿综合征属周围神经系统疾病,分原发性和继发两种类型。大多发生于终末期肾脏病(ESRD)或患者开始透析治疗以后,症状较原发性患者重。但具体发病机制迄今仍然尚不清楚。本文就终末期肾病透析患者不安腿综合征病因、发病机制、临床表现、检查、诊断、治疗及目前进展情况作一综述。     

Pharmacology of vecuronium in patients with end-stage renal failure

Vecuronium was administered as an intravenous bolus (50 micrograms kg-1) to 10 normal and 10 anephric patients. The elimination half-life was 50.7 +/- 20.3 min in normal patients and 67.826.3 min in anephric patients. The plasma clearance was 3.6 +/- 1.5 ml min-1 for normal patients and 4.5 +/- 2.6 ml min-1 kg-1 for anephric patients. Only the volume of the second compartment was statistically increased (+90%, P less than 0.05) in anephric patients. The duration of action in normal patients (25.3 +/- 9.8 min) was comparable to the duration of action in patients with renal failure (32.8 +/- 10.7 min), but the recovery index was prolonged (+45%, P less than 0.05) in anephric patients.     

Pharmacokinetics of pantoprazole in patients with end-stage renal failure

Background: Pantoprazole is a selective inhibitor of the gastric H⁺/K⁺-ATPase with a low potential to interact with the cytochrome P450 enzyme system. Since pantoprazole is metabolized in the liver to metabolites which are mainly cleared by the renal route, it was the aim of this study to investigate its pharmacokinetics in patients with end-stage renal failure undergoing regular haemodialysis. Methods: Eight patients with end-stage renal failure (creatinine clearance <5 ml/min, age 45-65 years) on regular haemodialysis (duration of haemodialysis 4-5 h, cuprophan-dialyser Hemoflow E3, surface 1.3 m²) were given single i.v. doses of 40 mg pantoprazole one day before haemodialysis (A) and on a haemodialysis day immediately before the start of the haemodialysis (B). Concentrations of pantoprazole and metabolite M2 were determined in plasma and urine over 24 h and in timed samples of the dialysis fluid by HPLC. The protein binding was determined using equilibrium dialysis. Results: The pharmacokinetic characteristics of pantoprazole AUC, t½, CL and Vd area (geometric means) were 2.4 mgxh/l, 0.63 h, 0.227 l/h/kg and 0.206 l/kg on day A (without dialysis) and 2.3 mgxh/l, 0.8 h 0.237 l/h/kg and 0.273 l/kg on day B (with dialysis), respectively. The protein binding was 96%. Pantoprazole was found in small amounts in the dialysis fluid (max. 2.1% of the dose) but not in the urine. Pantoprazole was well tolerated. In particular, there were no clinically relevant changes in blood count, electrolytes or liver enzymes. Conclusions: Haemodialysis has no influence on the pharmacokinetic characteristics of pantoprazole. Thus, pantoprazole is not dialysed to any relevant degree, and therefore no dose-adjustment is required for patients with endstage renal failure undergoing regular haemodialysis treatment.     

Difficult vascular access in patients with end-stage renal failure

BACKGROUND/AIM: End-stage renal failure patients requiring long-term hemodialysis need a durable vascular access. The arteriovenous fistula (AVF) with its long patency rate and low complication profile is usually the first choice for vascular access creation. However, when superficial veins are not suitable for AVF creation or all have been exhausted as a result of repeated AVF procedures, arteriovenous grafts (AVGs) using expanded polytetraflouroethylene (ePTFE) is an alternative. This study reviewed our experience in using PTFE AVGs for vascular access in patients requiring chronic hemodialysis. MATERIALS AND METHODS: In a prospective study, from September 2002 to October 2004, 21 PTFE AVGs were placed in 21 patients. We evaluated the complications and patency. RESULTS: There were 12 female and nine male patients of mean age 58+/-8.7 years (range=45 to 76 years). Nine patients (43%) had hypertensive nephrosclerosis, 6 (29%) diabetic, 2 (10%) glomerulonephritis, 3 (14%) systemic lupus erythematosis requiring long-term steroids, and 1 (4.7%) unknown cause. The patency rate at 24 months was 85.7%. Complications included graft thrombosis (three; 14.3%), wound infection (three; 14.3%) and graft infection (one; 4.8%). CONCLUSION: ePTFE AVGs offer reasonable patency and serviceability rates as a vascular access modality, but in view of their complication profile, the native vein arteriovenous fistula should continue to be the first choice for vascular access for patients requiring chronic hemodialysis.     

Pharmacokinetics of mycophenolate mofetil in patients with end-stage renal failure

BACKGROUND: Mycophenolate mofetil (MMF) acts as a prodrug for the immunosuppressive drug mycophenolic acid (MPA). It is rapidly converted to MPA following oral ingestion. MPA is metabolized to MPA glucuronide (MPAG), which is renally excreted. This study examines the pharmacokinetics of MPA and MPAG in patients with end-stage renal failure who were on hemodialysis (N = 10) or peritoneal dialysis (N = 10) treatment. METHODS: After an overnight fast, a single oral dose of 1 g MMF was given. Plasma concentrations of MPA and MPAG were measured from 0 (predose) to 36 hours after administration, using high-performance liquid chromatography (HPLC). The area under the concentration time curve (AUC) from 0 to 36 hours was calculated using the trapezoidal rule. RESULTS: Mean (+/- SD) AUC for MPA was 55.7 +/- 32.6 mg/L.h for hemodialysis patients and 44.7 +/- 14.7 mg/L.h for peritoneal dialysis patients, which is similar to expected values for subjects with normal renal function. The mean (+/- SD) maximum plasma concentration (Cmax) for MPA was lower than would be expected for subjects with normal renal function (16.01 +/- 10.61 mg/L for hemodialysis, 11.48 +/- 4.98 mg/L for peritoneal dialysis). MPAG clearance was prolonged with AUC approximately five times what would be expected in subjects with normal renal function (1565 +/- 596 mg/L.h for hemodialysis, 1386 +/- 410 mg/L.h for peritoneal dialysis). There was no significant difference for any of the pharmacokinetic parameters between subjects on hemodialysis and those on peritoneal dialysis. Plasma concentrations of MPA and MPAG did not fall significantly during hemodialysis. No MPA was detectable in hemodialysis or peritoneal dialysis fluid, but small amounts of MPAG were detected in hemodialysis fluid in 1 out of 10 subjects and in peritoneal dialysis fluid in 3 out of 10 subjects. CONCLUSIONS: The accumulation of MPAG may be responsible for the poor gastrointestinal tolerance of this drug in dialysis patients and probably limits the maximum dose of MMF that can be tolerated.     

Adaptation of glutathion-peroxidase activity to oxidative stress occurs in children but not in adult patients with end-stage renal failure undergoing hemodialysis

Lipid peroxidation (LPO) products formed after reaction of free radicals with membrane lipids are involved in the pathogenesis of cardiac diseases. Also in patients with end-stage renal disease (ESRD) LPO was shown to be accelerated and concentrations of non-enzymatic antioxidants were measured lower than in control subjects. However, up to now only limited knowledge about the role of antioxidant enzymes was available. Whether or not activity of those antioxidants might be induced due to oxidative stress in ESRD patients is not known. To answer the question the activity of 3 enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), and glutathion peroxidase (GPx), was measured in red blood cells of the ESRD patients undergoing hemodialysis (2 groups: children and adults) and matching controls. LPO in these subjects was determined by measurement of the LPO product 4-hydroxynonenal (HNE) in blood plasma. Plasma HNE was significantly increased by factor 3 in both patient groups children and adults compared to the control groups. The activity of the enzymatic antioxidants was measured differently. While SOD was significantly lower in patients (children and adults) than in the matching controls this was not the case for catalase and GPx. While GPx activity in adult patients was comparable to that in the control groups (childrens and adults), the GPx in children with ESRD was almost twice as high than in the other groups. Since children were shown to have higher levels of glutathion, activated GPx might be a sign of adaptation of these children to the increased rate of oxidation.