Long-term Dialysis Patients Research Articles

Microfocus Computed Tomography Analysis of Early Changes in Bone Microstructure in Rats with Chronic Renal Failure

Background/Aims: Little is known about the microstructural changes in bone tissue in the early phase of chronic renal failure (CRF). In this study, we analyzed the bone tissue in a rat model of early CRF using a high-resolution X-ray tomographic system, i.e. microfocus computed tomography (MXCT), which is capable of detecting microscopic structural changes in bone tissue. Methods: CRF rats were created by 7/8 nephrectomy by ligation of the renal artery branches, and were sacrificed 24 weeks after surgery. MXCT and bone mineral densitometry by single-energy X-ray absorptiometry (SXA) were performed using extracted bone samples. Images obtained by MXCT were further analyzed by node-strut morphometry. Results: Biochemical analysis confirmed that CRF was induced in 7/8-renal artery-ligated rats. MXCT demonstrated a significant decrease in trabecular bone in uremic rats, whereas SXA was unable to detect the difference. The node-strut method revealed decreased trabecular connectivity, with little change in the thickness of the trabecular bone in uremic rats. Conclusion: MXCT was able to detect significant changes in trabecular bone at an early stage of renal failure. The observed structural changes differed from those found in long-term dialysis patients. MXCT is a practical and promising device used for the non-invasive evaluation of early bone changes in uremic patients.

Gabapentin-induced hypoglycemia in a long-term peritoneal dialysis patient

An end-stage renal disease patient on long-term peritoneal dialysis was admitted with dizziness, fatigue, hypoglycemia, and hypotension. The hypotension resolved with intravenous normal saline, but the hypoglycemia persisted for 3 days despite an intravenous dextrose drip and discontinuation of gabapentin. The patient became normoglycemic on the fourth day of admission. None of the known causes for the hypoglycemia were identified except gabapentin, the dose of which was recently doubled 1 month before admission. Insulin and C-peptide levels were high during the hypoglycemic episode and returned to normal after discontinuation of gabapentin. The patient remains off gabapentin and has had no further episodes of hypoglycemia. To our knowledge, this is the first case of hypoglycemia induced by gabapentin.

Effect of β2-microglobulin adsorption column on dialysis-related amyloidosis

beta2-microglobulin (beta2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle, an adsorption column, has been developed for the elimination of beta2-m; the efficacy of this column has been evaluated in this study. Seventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, beta2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated. After 1-year treatment with high-flux dialysis the beta2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle column, beta2-m level decreased significantly from 34.5 +/- 8.4 mg/L to 28.8 +/- 7.3 mg/L (P < 0.05). After 1 year of Lixelle column use, the pinch strength increased from 6.8 +/- 4.7 pounds to 9.1 +/- 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 +/- 1.0 mseconds to 4.5 +/- 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities. These results suggest that the addition of Lixelle to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.

Salivary and lacrimal secretion is reduced in patients with ESRD

Background:A reduction in salivary and lacrimal secretion has been described in several diseases. However, such alterations have not been investigated fully in patients with chronic renal failure. The aim of the present study is to estimate the frequency of alterations in salivary and lacrimal secretion in long-term hemodialysis patients. Methods:Sixty-three hemodialysis patients and 23 healthy control subjects were studied. In all of them, we tested salivary secretion (Saxon's test), lacrimal secretion (Shirmer's test), and the presence of xerostomia and xerophthalmia symptoms. In a subgroup of patients, we performed other tests to evaluate evidence of ocular lesions and tissue damage to salivary glands. We also tested the relationship between salivary and lacrimal secretion and autonomic nervous system function. Results:On average, salivary and lacrimal secretion were markedly reduced in uremic patients compared with healthy controls, and alterations in salivary gland function were related strongly to salivary gland fibrosis and atrophy. Xerophthalmia often was asymptomatic, but frequently was associated with corneal lesions. Xerostomia and xerophthalmia were unrelated to autonomic dysfunction and hepatitis C virus infection. Conclusion:A reduction in lacrimal and salivary secretion is frequent in long-term dialysis patients. Such alterations often are asymptomatic and could be the expression of acceleration of an age-dependent decline in glandular function and attendant fibrosis and atrophy.

Utility of in vitro closure time test for evaluating platelet-related primary hemostasis in dialysis patients

Background:The platelet aggregation and skin bleeding time (SBT) tests currently used for assessment of hemostasis impairment in dialysis patients have important disadvantages. The authors explored the utility of a novel in vitro closure time test (PFA-100, platelet function analyzer) in which the process of platelet adhesion and aggregation after vascular injury is simulated in vitro in dialysis patients. Methods:Thirty-four long-term dialysis patients were included in the study with 30 healthy volunteers as the control group. In vitro closure time was compared with results from the platelet aggregation and SBT tests. Results:In vitro closure time identified more patients and fewer controls with hemostasis impairment. In the patient group, 60%, 40%, and 20%, and in the control group, 0%, 10% and 3% of persons were found to have hemostasis impairment as determined by in vitro closure time, platelet aggregation, and SBT, respectively. In addition, values for patients and controls were significantly different for in vitro closure time (P < 0.05) but not for platelet aggregation or SBT. Thus, closure time appears to be more sensitive and specific than the other 2 tests. No correlation was found between the 3 tests, either in patients or in controls. However, a high correlation (r = 0.73; P < 0.0001) was found between the 2 types of in vitro closure time test (collagen/epinephrine [CEPI] and collagen/adenosine diphosphate [CADP]) in patients and controls. Conclusion:These results indicate that in vitro closure time can be a useful test for detecting platelet-related primary hemostasis defects in dialysis patients.

Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients

Background: Levels of advanced glycation end products (AGEs), well-known proinflammatory compounds, are markedly elevated in patients with renal failure, raising the speculation that they have a role as cardiovascular risk factors in this population. Although elevated AGE levels in patients with renal failure have been attributed to impaired renal clearance and increased endogenous AGE formation, recent data suggest an important role for diet as a source of AGEs. Methods: To determine the relationship between dietary AGE content and serum AGE levels, a cross-sectional study was performed in our long-term dialysis patients. Dietary AGE intake was estimated by means of dietary records and questionnaires, and sera were obtained for measurement of 2 well-characterized AGEs, carboxymethyl-lysine (CML) and methylglyoxal (MG) derivatives. Results: The study population included 189 patients; 139 hemodialysis and 50 peritoneal dialysis patients. Serum CML level correlated significantly with dietary AGE intake, based on either 3-day food records (r = 0.5; P = 0.003) or dietary questionnaires (r = 0.22; P = 0.03). Although no correlation was observed with nutrient intake (protein, fat, saturated fat, or carbohydrate), both serum CML and MG levels correlated with blood urea nitrogen (r = 0.2; P = 0.03 and r = 0.2; P = 0.02, respectively) and serum albumin levels (r = 0.16; P = 0.04 and r = 0.18; P = 0.02, respectively). Conclusion: Data indicate that dietary AGE content, independently of other diet constituents, is an important contributor to excess serum AGE levels in patients with renal failure. Moreover, the lack of correlation between serum AGE levels and dietary protein, fat, and carbohydrate intake indicates that a reduction in dietary AGE content can be obtained safely without compromising the content of obligatory nutrients.

Dietary self-efficacy: determinant of compliance behaviours and biochemical outcomes in haemodialysis patients.

Despite the diversity of proposed theories, researchers are still unable to fully explain dietary compliance behaviours of dialysis patients. Dietary self-efficacy, a concept less studied in dialysis, has been linked to positive compliance outcomes in the chronic illness literature. Therefore, the aim of the present research was to determine how dietary self-efficacy is related to selected biochemical markers and self-reported behavioural outcomes in haemodialysis patients. 107 subjects participated in a cross-sectional study. Four questionnaires assessed dietary self-efficacy, compliance attitudes and behaviours, and staff-patient relationships. Laboratory outcomes were retrospectively obtained from patients' medical records and averaged for the previous 6 months. Of the behavioural measures, only dietary self-efficacy was associated with laboratory outcomes. Dietary self-efficacy was also positively related to staff-patient relationships and to patients' self-reported assessment of compliance behaviours. Women had greater dietary self-efficacy than men. The number of family members living with the respondent was inversely related to dietary self-efficacy. Results indicated that dietary self-efficacy determined both behaviours and laboratory outcomes. Patients with greater dietary self-efficacy had lower serum potassium and weight gain, showed favourable compliance attitudes and behaviours toward prescribed regimens and fostered better relationships with staff. Based on these findings we recommend an experimental approach to clarify whether maximizing dietary self-efficacy efforts is without psychological burden to patients and whether the positive effect of increased dietary self-efficacy is maintained in long-term dialysis patients.

Depression and its association with peritonitis in long-term peritoneal dialysis patients

Background:Depression is the most common psychological disorder among patients with end-stage renal disease and has been associated with mortality in patients maintained on hemodialysis therapy. Peritonitis is the leading cause of technique failure among long-term peritoneal dialysis (PD) patients. This prospective study is designed to examine the relationship between depression and peritonitis. Methods:All patients on long-term PD therapy in our unit between January 1, 1997, and January 31, 2002, completed a Beck Depression Inventory (BDI) assessment at 6-month intervals. BDI scores were analyzed 2 ways. First, patients were placed into either group I (BDI score < 10) or group II (BDI score ≥ 11) and were reclassified based on subsequent scores. Second, multivariable analysis was performed looking at initial BDI score as a risk factor for peritonitis, adjusting for age older than 65 years, diabetes, coronary artery disease, and race. Results:One hundred sixty-two patients were enrolled, and 281 individual BDI assessments were completed. There was a significantly greater incidence of diabetes and coronary artery disease in group II. Rates for overall and gram-positive peritonitis were significantly greater in group II patients compared with group I patients. Using Cox regression, only BDI score of 11 or greater was associated with the development of peritonitis (hazard ratio, 2.7; 95% confidence interval, 1.2 to 6.0). Conclusion:There is an association between BDI score of 11 or greater and the development of peritonitis. Whether treatment of depression can impact on the rate of peritonitis remains to be examined.

Inhibition of the interaction of AGE-RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane.

The peritoneal membrane of long-term peritoneal dialysis patients is characterized by a loss of ultrafiltration capacity, associated morphologically with submesothelial fibrosis and neoangiogenesis. Exposure to high glucose concentrations in peritoneal dialysate and the resultant advanced glycation end-products (AGE) accumulation have been implicated in the development of these changes, but their exact pathophysiological role is unknown. We examined the effect of the interaction of AGE with one of their receptors (i.e., RAGE) on the function and structure of the peritoneum exposed to high ambient glucose concentrations. Streptozotocin-induced diabetic rats and control rats were treated during 6 wk with either neutralizing monoclonal anti-RAGE antibodies or control antibodies. The expression of RAGE was strongly enhanced in the peritoneal membrane of the diabetic animals. The diabetic peritonea were characterized by an elevated transport of small solutes, lower ultrafiltration rates, a higher vascular density, and an upregulation of endothelial nitric oxide synthase expression. These parameters were unaffected by treatment with anti-RAGE antibodies. In contrast, anti-RAGE but not control antibodies prevented upregulation of TGF-beta, development of submesothelial fibrosis, and fibronectin accumulation in the peritoneum of diabetic animals. In conclusion, binding of AGE to RAGE increases the expression of TGF-beta and contributes to the development of submesothelial fibrosis. Neoangiogenesis and the resultant loss of ultrafiltration capacity are mediated by different pathogenetic pathways.

High glucose activates the p38 MAPK pathway in cultured human peritoneal mesothelial cells

Peritoneal fibrosis is a serious complication in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, but the underlying mechanism is not well understood. Since high glucose activates the p38 mitogen-activated protein kinase (MAPK) pathway in various kinds of cells, and because mesothelial cells are always exposed to high glucose dialysate, we examined the activity and expression of p38 MAPK members in cultured human peritoneal mesothelial cells (HPMCs) under high glucose conditions. HPMCs were isolated from omentum and subcultured. After serum restriction, HPMCs were exposed to 5.6 mmol/L glucose (low glucose), 5.6 mmol/L glucose + 34.5 mmol/L mannitol (low glucose + mannitol), or 40 mmol/L glucose (high glucose) for 3 minutes to 48 hours with or without SB203580. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine mRNA and protein expression, respectively. p38 MAPK and cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB) activities and mRNA expressions were significantly increased in HPMCs exposed to high glucose compared to low glucose or low glucose + mannitol after 10 minutes and remain at higher levels to 48 hours (P < 0.05), but total p38 MAPK and CREB protein expressions did not differ. MAPK kinase 3/6 (MKK3/6) activity and mRNA expression were also higher in high glucose cells after 3 minutes (P < 0.05), and fibronectin mRNA expression was significantly increased in HPMCs exposed to high glucose after 2 hours (P < 0.05). In contrast, high glucose significantly inhibited MAPK phosphatase-1 (MKP-1) protein and mRNA expression after 10 minutes (P < 0.05). SB203580 (1 micromol/L) pretreatment for 1 hour significantly reduced high glucose-induced CREB activity and fibronectin mRNA expression by 89% and 75%, respectively (P < 0.05). p38 MAPK activity was increased in HPMCs exposed to high glucose, in parallel with increased MKK3/6 activity and decreased MKP-1 expression, resulting in CREB activation. This activated p38 MAPK pathway may play a role in the pathogenesis of peritoneal fibrosis.

Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study.

Calcification complications are frequent among long-term dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean +/- SD age, 55 +/- 12 yr) on continuous ambulatory peritoneal dialysis (mean +/- SD duration of dialysis, 39 +/- 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P < 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P < 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased all-cause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P < 0.0005). The number of calcified valves was associated with all-cause mortality (P < 0.0005) and cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome.

Peritoneal mesothelial cell biology in peritoneal dialysis

SUMMARY: Progressive peritoneal membrane hyperpermeability, ultrafiltration failure, and peritoneal fibrosis have been observed in long‐term peritoneal dialysis (PD) patients, and these alterations in peritoneal structure and function may be responsible for the poor technique survival in PD. While frequent and/or severe peritonitis can result in alterations of the peritoneum, continuous exposure of the peritoneum to PD solutions may also adversely affect peritoneal structure and function. Peritoneal mesothelial cells (PMC) are directly and continuously exposed to unphysiological components of PD solution. Low pH, lactate, hyperosmolality, and glucose degradation products (GDP) reduce PMC viability and proliferation. High glucose, GDP, and advanced glycation end products (AGE) upregulate vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)‐1, transforming growth factor (TGF)‐β1, plasminogen activator inhibitor (PAI)‐1, and extracellular matrix protein expression by PMC, and may thus lead to peritoneal hyperpermeability, ultrafiltration failure, and peritoneal fibrosis, as observed in long‐term PD. Activation of diacylglycerol (DAG)‐protein kinase C (PKC) and generation of reactive oxygen species (ROS) are important upstream signalling events in high glucose‐induced PMC activation. Thus, strategies to inhibit high glucose‐induced PKC activation and ROS generation and the use of new PD solutions with non‐glucose osmotic agents, pH neutral solutions, or solutions containing low GDP may allow better preservation of the structural and functional integrity of the peritoneal membrane during long‐term PD.

Clinical development of OCT

OCT was first synthesized in the late 1980s, and clinical development was started in July 1991 with entry into Phase I. By the time the application for manufacturing approval was submitted, in February 1998, 15 clinical studies had been carried out, including 2 double-blind comparative studies and 5 long-term administration studies. The efficacy and safety of OCT were evaluated on the basis of clinical data obtained from totally 977 participants. OCT was found to be effective against secondary hyperparathyroidism in long-term dialysis patients, as it markedly decreased the PTH level, and showed ameliorative effects in bone tissue showing high bone turnover, and on bone metabolic markers. Adding to above clinical effects, because safety data demonstrated that there was no significant drawback except for an increase of serum calcium level, manufacturing approval was finally achieved in July 2000, under the commercial name "Oxarol injection".

Peritoneal calcifications in a patient on continuous ambulatory peritoneal dialysis

Complications in a long-term ambulatory peritoneal dialysis patient are described.

Effect of hemodialysis on the oxidative stress and antioxidants.

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.

長期透析患者の頚椎病変に対する手術治療成績

Dialysis-associated spondylosis is increasingly recognized in long-term dialysis patients. We reviewed 13 patients who had dialysis-associated cervical spondylosis and required surgical treatment. There were 7 males and 6 females with an average age of 55 years (range 38 to 77). The duration of hemodialysis ranged from 8 to 26 years (mean : 17.2 years) and the follow-up time ranged from 6 months to 6 years and 9 months, averaging 3 years. We performed anterior fusions on 4 cases, laminoplasty on 7 cases, posterior fusion on 1 case and occipito-cervical fusion on 1 case. In 12 cases (excluding 1 case of AAS), we assessed the clinical results by the JOA score and the recovery rate using Hirabayashi’s method. The mean recovery rate was 46%. Eight of the 13 cases had good to excellent results, 3 had fair, and 2 poor. The cases with poor results developed by post-operative infection in the operative wound, and died at 7 and 17 months after operation respectively.

Chronic Fatigue in Long-Term Peritoneal Dialysis Patients

Objective: Fatigue is a common symptom in long-term dialysis patients. This study investigated possible clinical factors which may cause the development of fatigue in patients receiving peritoneal dialysis (PD). We also investigated the relationship between total solute clearance (TSC) and fatigue symptoms in PD patients. Design: A cross-sectional study design was used to compare the clinical characteristics among groups of PD patients classified by different degrees of fatigue. The relationship among dialysis adequacy (including Kt/V_urea and weekly creatinine clearance; C_cr), clinical characteristics and fatigue symptoms were also assessed. Setting: The PD unit of a major university teaching hospital in Taipei, Taiwan. Patients: Consecutive patients who had received PD for a minimum duration of 4 months were recruited for participation in the study. Patients were excluded if they had a history of ischemic heart disease, severe heart failure (NYHA function III or IV), malignant neoplasm, active infection, major psychiatric problems, chronic obstructive pulmonary disease, or disturbed consciousness. Finally, a total of 64 patients, 31 of whom were receiving continuous ambulatory peritoneal dialysis and 33 who were receiving continuous cycling-assisted peritoneal dialysis, were enrolled in the study. Methods: Fatigue was evaluated using a specially designed questionnaire that includes fourteen items. Patients were divided into three groups according to their fatigue scores (FS): mild (FS, 0–3), moderate (FS, 4–8), and severe (FS, 9–14) fatigue. The demographic data, dialysis variables, and clinical parameters of patients were compared among these groups. The relationship between fatigue and TSC was also examined. Results: The FS were correlated with serum intact parathyroid hormone (iPTH) level and total cholesterol concentration (p < 0.05). A linear correlation was also noted between serum iPTH level and total cholesterol level. When the patients were divided into an adequate- and an inadequate-dialysis group according to values of TSC, Kt/V_urea as well as weekly creatinine clearance, a significant correlation was found between weekly C_cr and FS. Conclusion: This study has demonstrated that dialysis adequacy plays a key role in the development chronic fatigue. In addition, weekly C_cr was better correlated with fatigue than Kt/V_urea.

High Glucose Dialysis Solutions Increase Synthesis of Vascular Endothelial Growth Factors by Peritoneal Vascular Endothelial Cells

Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% +/- 19%, p = 0.006) as compared with the control and mannitol (85% +/- 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% +/- 49%) than in the control and mannitol (94% +/- 18%) groups. High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.

Comparison of intact PTH assay and whole PTH assay in long-term dialysis patients

Adynamic bone disease has become a major problem in long-term dialysis patients. It has been suggested that higher levels of parathyroid hormone (PTH) are needed to maintain normal bone turnover in uremia. PTH levels currently are evaluated routinely by intact PTH assay, which may detect inactive 7-84 PTH fragments as well as 1-84 PTH. We examined the efficacy of whole PTH assay, which detects 1-84 PTH exclusively, in 99 nondiabetic patients on maintenance dialysis for more than 10 years, without any residual renal function. PTH levels determined by whole PTH assay were lower than those determined by intact PTH assay in all cases. Serum markers of bone metabolism, such as serum activity of bone alkaline phosphatase, correlated well with whole PTH levels. Because 7-84 PTH has been shown to inhibit the effects of 1-84 PTH, the biologic activity of circulating PTH in uremic patients may be much lower than the values assayed by conventional intact PTH assay. Despite an attempt to correlate 1-84 PTH/7-84 PTH ratio with bone histology, we could find only 1 patient out of 99 with 1-84 PTH/7-84 PTH ratio less than 1, which has been suggested to be indicative of low turnover bone. A cutoff value of this ratio should be set in the future for patients with a long hemodialysis history, with various modes of medical therapy. © 2001 by the National Kidney Foundation, Inc.

Effect of erythropoietin on cardiovascular diseases

Cardiac diseases account for almost 50% of deaths in long-term dialysis patients. Left ventricular dysfunction is present in approximately 80% of these patients and is highly predictive of future ischemic heart disease, cardiac failure, and death. Anemia has been identified as one of several risk factors responsible for cardiac complications. Cardiovascular consequences of renal anemia begin relatively early in the course of renal failure and progress with the decline of renal function and also during dialysis therapy. In chronic renal failure patients with severe anemia (hemoglobin levels <10 g/dL), increased cardiac output, high left ventricular mass, left ventricular end-diastolic and end-systolic diameters, and cardiac symptoms improve after partial correction of anemia (hemoglobin levels >11 g/dL according to the European Best Practice Guidelines). It is disappointing that normalization of hemoglobin levels has only minor effects with respect to regression of left ventricular hypertrophy and left ventricular dilation. There is no benefit of hemoglobin normalization on all-cause mortality of dialysis patients or on survival of end-stage renal disease patients with congestive heart failure or ischemic heart disease. Therefore, prevention of renal anemia may be more efficient than its treatment. Hypertension is one of the major side effects of recombinant human erythropoietin (rHuEPO) therapy. Multiple factors are involved in rHuEPO-induced hypertension. High blood pressure can usually be controlled readily in the majority of the patients. © 2001 by the National Kidney Foundation, Inc.