Polyamines in the anemia of end-stage renal disease

The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera from patients with ESRD inhibited erythroid colony (CFU-E) (N = 10) formation to a significantly (P less than 0.01) greater degree than granulocyte-macrophage (CFU-GM) (N = 7) colony formation in mouse bone marrow (MBM) cultures. The polyamines spermine (SP) (18 to 560 nm/ml) and spermidine (SD) (4 to 648 nm/ml) exerted a more significant (P less than 0.05) inhibition of CFU-E (N greater than or equal to 5) than that of CFU-GM (N greater than or equal to 5) growth. Concentrations of 0.80, 1.0, and 1.5 nm/ml of putrescine (PU) were 92%, 85%, and 77% of erythroid colony (CFU-E) controls (N = 4) and 104%, 130%, and 127% of CFU-GM controls (N = 4). Putrescine (PU) at 1.5 nm/ml also produced a significant (P less than 0.05) inhibition of CFU-E, whereas CFU-GM were stimulated by PU. These data suggest that predialysis sera from uremic patients, as well as SP, SD, and PU, are selectively more inhibitory to CFU-E than CFU-GM growth. The immunoreactivity of EPO was not significantly changed when it was coincubated with SP, SD and PU and measured by radioimmunoassay. PU was found to inhibit noncompetitively the bioactivity of EPO in a CFU-E assay. These data support the hypothesis that polyamines may be important uremic toxins in the anemia of ESRD.     

The impact of anemia correction on cardiovascular disease in end-stage renal disease

Cardiovascular disease is a major cause of mortality and morbidity in patients with end-stage renal disease. Anemia, a result of erythropoietin deficiency, is associated with increased all-cause and cardiovascular mortality in this population, and predisposes patients to the development of symptomatic heart disease. Anemia is also associated with the development and progression of left ventricular echocardiographic disorders, which strongly predict cardiac failure and death. Left ventricular dilatation with compensatory hypertrophy, the major pattern of echocardiographic disease progression in hemodialysis patients, is a particularly strong predictor of late mortality. Partial correction of anemia with recombinant human erythropoietin likely reduces left ventricular mass and volume. Complete correction of anemia may prevent progressive left ventricular dilatation in patients with normal left ventricular volumes. A recent trial, however, reports excess mortality and vascular access loss in patients with preexisting symptomatic heart disease when anemia was completely corrected. Consequently, hematocrit target ranges above 32% to 36% cannot be recommended in this population. In patients without symptomatic heart disease, it is not possible to conclude that potential benefits derived from a normalized hematocrit will outweigh potential risks.     

Erythropoietin-hematocrit feedback circuit in the anemia of end-stage renal disease

Deficient erythropoietin (EP) production is thought to be a key factor in the pathogenesis of the anemia of end-stage renal disease. We describe the interrelationships between radioimmunoassayed plasma EP levels, reticulocyte counts corrected for anemia (CRC) and hematocrit (HCT) under challenge by hemorrhage, transfusions and hemodialysis in 32 chronically-hemodialyzed patients. Spontaneous hemorrhage resulted in a decrease in HCT (P = 0.001) and increases in both EP (P = 0.006) and CRC levels (P = 0.0065). Transfusions of two units of packed red cells into each of 16 patients suppressed EP (P = 0.0004) and CRC (P less than 0.0001) after about 28 and 42 hours, respectively. Repeat transfusions after one to 27 days resulted in similarly significant suppressions of both EP and CRC, except the CRC remained on higher levels for prolonged periods of times. Within a few hours after each transfusion of 2,3-diphosphoglycerate-poor red cells, both EP (P = 0.009) and CRC (P = 0.007) increased temporarily between one to 18 and three to 38 hours, respectively. Hemodialysis resulted in alkalinization (P = 0.008) of blood but not in changes of EP or CRC counts. The data show that, with the EP-HCT feedback loop persisting, increased endogenous hormone levels elicit erythropoietic responses, and that the regulation of EP levels may involve determinants such as oxy-deoxyhemoglobin interactions.     

The clinicopathological characteristics in renal cell carcinoma with end-stage renal disease

OBJECTIVES: The influence and the interdependence of pathological and clinical factors on prognostic differences between renal cell carcinoma (RCC) with end-stage renal disease (ESRD) and RCC without ESRD after nephrectomy has remained unclear. We compare the clinicopathological features between RCC with and without ESRD. MATERIALS AND METHODS: From June 1993 to May 2000, 150 RCC patients who underwent nephrectomy were pathologically defined to have pT1 to pT3NXM0. The patients were followed for 1 to 84 months (median 30 months) after the surgery. Total of 16 patients with ESRD and 134 patients without ESRD were studied, and the differences of clinicopathological features between two groups were statistically compared. RESULTS: We compare the clinicopathological features between RCC with and without ESRD. Patients' age, tumor size, rate of incidental cancer, pathological T stage, and grade were not significantly different between two groups. The 5-year recurrence-free probability rate was significantly higher in patients without ESRD than in patients with ESRD (log-rank test: p = 0.04). The status of ESRD, patients age and pathological T stage were significant predictors of recurrence when analyzed by Cox proportional hazards analysis (p = 0.01, p = 0.03 and p = 0.02, respectively). CONCLUSIONS: This study demonstrated that the ESRD is an independent prognostic factor in RCC patients after surgery. These results reflect that the patients with ESRD have higher risk of tumor progression. Therefore, early detection of tumors is particularly important in these patients by regular abdominal ultrasound or CT screening.     

Refractory hypertension and anemia in end-stage renal disease: an unusual manifestation of Kimura's disease

Hypertension and anemia are common in uremic patients. This article describes a 35-year-old uremic Taiwanese who was admitted to our hospital with refractory hypertension and refractory anemia following chronic hemodialysis for more than two years. He was diagnosed with Kimura's disease finally. Refractory hypertension and refractory anemia were noted over two years before an enlarged inguinal lymph node was observed. The symptoms lead to the diagnosis of Kimura's disease. Unlike most cases, refractory hypertension and refractory anemia were first noted before the inguinal mass and eosinophilia were presented. The inflammatory parameters increased when the disease was active. Steroid treatment was conducted, and the symptoms including hypertension and anemia promptly decreased. To the authors' knowledge, this case is for first one in which Kimura's disease has induced refractory hypertension and anemia in an ESRD patient and in which these symptoms rapidly subsided following steroid treatment. The activity of Kimura's disease is closely related refractory hypertension, suggesting that inflammation may be involved in refractory hypertension and anemia in a dialytic patient with Kimura's disease.     

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.     

Candidate biomarkers for erythropoietin response in end-stage renal disease

Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is important clinically and economically. Escalation of dose may produce harm. Post hoc analyses of clinical trials showed that responsiveness could be predicted by hemoglobin response to a fixed dose escalation. This maneuver requires weeks to months. The study by Merchant et al. offers promise that peptidomic analyses of patient sera and mass spectrometry can identify biomarkers of both responsiveness and resistance to ESAs.     

The adolescent with end-stage renal disease

The adolescent with ESRD is frequently immature in relationship to chronological age. Growth and pubertal development are major concerns for the adolescent with ESRD. If renal failure had its onset prior to adolescence, it is likely that puberty will be delayed and ultimate adult height retarded for the patient requiring ESRD care during the adolescent period. Non-compliance with the therapeutic regimen is a major clinical problem encountered in the management of the adolescent. Significant morbidity can result from non-compliance with the dialysis regimen and non-compliance is a major cause of allograft loss in the adolescent transplant recipient. The special needs of the adolescent must be considered if ESRD care is to be successful.     

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma

Clinical and Experimental Nephrology - The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. Patients diagnosed with...     

Effect of peritoneal dialysis versus hemodialysis on renal anemia in renal in end-stage disease patients: a meta-analysis

The aim of this meta-analysis was to evaluate the effect of peritoneal dialysis (PD) and hemodialysis (HD) on renal anemia (RA) in renal disease patients by a meta-analysis. Relevant studies published before June 2015 were searched. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the effect of HD and PD on RA based on five indexes: hemoglobin, ferritin, transferrin saturation index, serum albumin, and parathyroid hormone. Sensitivity analysis and publication bias assessment were conducted to evaluate the stability and reliability of our results. A total of fourteen eligible studies with 1103 cases underwent HD and 625 cases underwent PD were used for this meta-analysis. There were no significant difference for levels of hemoglobin (SMD?=??0.23, 95% CI: ?0.74 to 0.28), ferritin (SMD?=?0.01, 95% CI: ?0.59 to 0.62), parathyroid hormone (SMD?=?0.11, 95% CI: ?1.53 to 1.75) and transferrin saturation index (SMD?=??0.06, 95% CI: ?0.67 to 0.56) between HD and PD group. However, the content of serum albumin in HD group was much more than that in PD group (SMD?=?1.58, 95% CI: 0.35 to 2.81). Neither of the included studies could reverse the pooled side effect and Egger’s test demonstrated no publication bias. Both of the two dialysis strategies have a similar effect on RA in renal disease patients.     

A multicenter clinical trial of epoetin beta for anemia of end-stage renal disease

Patients with anemia of end-stage renal disease were studied for 36 weeks to determine efficacy, safety, and long-term benefits of epoetin beta administration. A total of 131 patients participated in the 12-week, double-blind, placebo-controlled portion of the multicenter study. For the first 6 weeks (fixed-dose period), patients were randomized to receive 100 U/kg of epoetin beta or placebo thrice weekly; in the second 6 weeks (dose-adjustment period), the dose of epoetin beta ranged from 50 to 150 U/kg thrice weekly. Of the 131 patients who entered the placebo-controlled period, 122 crossed over to a 24-week open-label period, where all patients received active drug and doses of epoetin beta could be individually titrated after the first 6 weeks. One hundred patients completed the 36-week study. In all phases of the study, epoetin beta was shown to produce a consistent, sustained increase in hemoglobin (baseline, 7.1 +/- 0.1 to 10.5 +/- 0.2 g/dL) and hematocrit (baseline, 21.5 to 32.7%), which virtually eliminated the need for packed red blood cell transfusions. Reticulocyte counts rose initially in response to epoetin beta and stabilized at levels higher than baseline throughout the remainder of the study period (baseline, 1.7 to 2.5%). The placebo group showed no change in these parameters during the double-blind period. Similar patterns of response were seen in the original placebo group after crossover to active drug (mean hemoglobin increase, 2.6 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.     

The safety of heparins in end-stage renal disease

In patients on chronic dialysis, unfractionated heparin (UFH) is the most commonly used agent for anticoagulation of the hemodialysis extracorporeal circuit, for hemodialysis catheter "locking" between dialysis treatments, and for nondialysis indications such as venous thromboembolic disease, peripheral vascular disease, and acute coronary artery disease. Potentially serious complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia, have led to consideration of other options for anticoagulation, including low molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can be used for anticoagulation of the hemodialysis circuit, but whether this has significant benefit compared to UFH remains to be proven. Because of the somewhat unpredictable risk of severe bleeding complications when LMWH is used for other indications in dialysis patients, UFH rather than LMWH is preferred for treatment of thromboembolic disease in these patients. DTIs have been used for anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT), with argatroban being the preferred agent if heparin-free hemodialysis cannot be performed. UFH still remains the preferred anticoagulant in the vast majority of dialysis patients requiring systemic anticoagulation and for anticoagulation of the extracorporeal hemodialysis circuit.     

Hyperphosphatemia in end-stage renal disease

Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD.     

Exercise in end-stage renal disease

Available studies indicate that exercise tolerance in renal patients is low. Although significant improvements in maximal oxygen consumption have been reported following exercise training in these patients, there may be physiologic limitations to the attainable levels of aerobic capacity due to the multisystemic nature of the disease. Long-term exercise training may result in other medical benefits. Compliance to regular exercise in hemodialysis patients remains a problem, however, exercise training during the dialysis treatment may prove beneficial in terms of compliance and supervision.     

Thrombosis in end-stage renal disease

Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.     

Hyperthyroidism in end-stage renal disease

We report the 2nd patient to have hyperthyroidism while on maintenance hemodialysis. This case is instructive because the diagnosis of hyperthyroidism in uremic patients is difficult due to similar signs and symptoms. This case report describes, for the first time, the unique interaction between hemodialysis and thyrotoxic heart disease. Paroxysmal atrial fibrillation and severe hypotension interfered with all hemodialyses. Only the correction of the hyperthyroid state and withdrawal of all beta-blocking agents allowed resumption of normal hemodialysis. The delayed gastric emptying and hypercalcemia ultimately resolved with return to the euthyroid state and did not recur during 10 months of follow-up.