Moderate metabolic acidosis and its effects on serum parameters in hemodialysis patients

We screened the laboratory data of 50 chronic hemodialysis patients selected randomly over a 21-month period to generate 158 data points which identified two groups: (1) those with a predialysis total CO(2) concentration less than or equal to 19 mEq/l (data A; n = 57) and (2) those with a predialysis total CO(2) concentration greater than 19 mEq/l (data B; n = 101). Then, both groups were compared for the following parameters: predialysis blood urea nitrogen (BUN), serum phosphorus, uric acid, creatinine, and albumin concentrations, Kt/V, urea reduction ratio, normalized protein catabolic rate, dry weight, ultrafiltration, blood flow and dialysis flow rates, duration of dialysis treatment, and blood pressure. Group data A had significantly higher predialysis BUN, phosphorus, and uric acid concentrations than group data B. There were significant inverse correlations between predialysis serum bicarbonate and predialysis BUN, phosphorus, and uric acid concentrations. Although it is not clear what the long term side effects of moderate metabolic acidosis are, we recommend its correction.     

HLA antigens and serum ferritin in hemodialysis patients

The evolution of serum ferritin levels in 111 chronic-hemodialysis patients is prospectively studied. Patients were classified in two groups according to the presence or absence of 'hemochromatosis antigens' (HLA A3, B7 or B14) in their HLA typing. Levels of serum ferritin were similar in both groups before they started dialysis and during the first year. On the contrary, in the second and third hemodialysis years serum ferritin was higher in the group carrying 'hemochromatosis antigens'. These differences were observed in patients treated with parenteral iron either in the form of transfusions or as intravenous dextran-iron but not in patients receiving oral iron. We conclude that the risk of developing iron overload is greater in hemodialysis patients with HLA A3, B7 or B14. Nevertheless, this potential risk can be minimized with a restrictive policy on the use of parenteral iron (transfusions, intravenous dextran-iron).     

Detection of novel beta 2-microglobulin in the serum of hemodialysis patients and its amyloidogenic predisposition

Serum from 8 undialyzed patients and 30 dialyzed patients was examined by immunoblotting using anti beta 2-microglobulin (beta 2M) serum after two-dimensional gel electrophoresis (2.DE). One major spot and three minor spots were detected in the ultrafiltrate as well as in the serum. One major spot was determined to be native beta 2M and three minor spots were found to be novel beta 2M. Novel beta 2M had a lower molecular weight (MW) and a higher acidic isoelectric point (pI). Novel beta 2M was recognized in the sera of 5 out of 20 hemodialysis (HD) patients without carpal tunnel syndrome (CTS), 2 of whom had been on HD from 5 to 10 years and 3 for more than 10 years, as well as in the sera of all 10 patients with CTS. By chromatofocusing, pI of novel beta 2M was 5.2, while pI of native beta 2M was 5.7. When the tissue specimen of transverse carpal ligament of 2 HD patients with CTS was examined by immunoblotting after 2.DE, the spot of novel beta 2M was larger than that of native beta 2M. It is possible that some metabolic abnormality of beta 2M occurs through long-term hemodialysis, and it is possible that novel beta 2M might relate to amyloidogenic predisposition.     

Flutamide-induced hepatic disorder and serum concentrations of flutamide and its metabolites in patients with prostate cancer

Severe hepatotoxicity occurred in a prostate cancer patient treated with 375 mg of flutamide per day, 125 mg three times a day, for 11 weeks. Serial measurements of serum concentrations of flutamide and its metabolites in the patient showed an unusually high serum level and delayed elimination of flutamide and suggested decreased metabolic activity of oxidation of flutamide to OH-flutamide. In 37 patients with prostate cancer we periodically monitored the serum concentrations of flutamide as well as liver function parameters. In 2 patients, glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) elevated over 100 IU/L, and treatment with flutamide was discontinued. Slight elevation of GOT and GPT over 40 to 100 IU/L was also detected in 5 patients, and flutamide was withdrawn. The elevated GOT and GPT in these 7 patients recovered to the pretreatment levels after discontinuation of the treatment. In these patients with flutamide-induced hepatic disorders, the average serum concentration of flutamide was higher (2.76 times, and that of OH-flutamide was lower (0.76 times), as compared with patients who maintained normal liver function.     

Cross-sectional and longitudinal predictors of serum albumin in hemodialysis patients

BACKGROUND: Lower serum albumin concentrations predict increased mortality in hemodialysis (HD) patients. Many demographic, comorbidity, and modifiable treatment-related factors that predict HD patient outcomes may be associated with serum albumin. METHODS: Cross-sectional predictors of baseline albumin on December 31, 1993 were sought (N = 3981). Additional effects of the same baseline predictors on subsequent trends in albumin over one year were examined in a nested subsample of patients (N = 2245). Wave-1 of the United States Renal Data System Dialysis Morbidity and Mortality special study provided the data. RESULTS: Significant associations (P < 0.05) are summarized as older age, female gender, peripheral vascular disease, chronic obstructive pulmonary disease, and cancer predicted a lower baseline albumin and negatively influenced subsequent albumin trends. Baseline albumin was higher for blacks (vs. whites), lower for smoking and diabetes, and lower during the first year of HD treatment (<3 months and 3 to 12 months, vs.> 1 year). Trend analysis showed more positive albumin slopes for patients in their first year on HD and more negative slopes for Native Americans (vs. whites). Baseline albumin was correlated with the type of vascular access being used [arteriovenous (AV) fistulas > AV grafts > permanent catheters > temporary catheters]. Trend analysis predicted more negative albumin slopes for AV grafts and permanent catheters (vs. AV fistula access). Baseline albumin correlated inversely with bicarbonate and directly with hematocrit. Dialysis with unmodified cellulose membranes, without reuse, predicted lower baseline albumin than the other membrane-reuse categories. CONCLUSIONS: Several exposures, which may be modifiable, were associated with serum albumin.     

Calcium acetate control of serum phosphorus in hemodialysis patients

Calcium acetate has many characteristics of an ideal phosphorus binder. It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above. One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate. We studied chronic (3-month) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers. All phosphorus binders were stopped for 2 weeks. Calcium acetate at an initial dose of 8.11 mmol (325 mg Ca2+) per meal was then used as the only phosphorus binder. Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L (5.5 mg/100 mL). Final calcium acetate dose was 14.6 mmol (586 mg) Ca2+ per meal. Sixteen patients developed mild transient hypercalcemia (mean, 2.84 mmol/L [11.4 mg/dL]. Initial phosphorus values in mmol/L (mg/dL) were 2.39 (7.4); at 1 month, 1.91 (5.9); and at 3 months, 1.68 (5.2). Initial calcium values in mmol/L (mg/dL) were 2.22 (8.9); at 1 month, 2.37 (9.5); and at 3 months, 2.42 (9.7). Initial aluminum values in mumol/L (micrograms/L) were 2.99 (80.7); and at 3 months were 2.54 (68.4). Initial C-terminal parathyroid hormone (C-PTH) values in ng/mL were 14.6; at 1 month, 11.9; and at 3 months, 13.2. Sixty-nine patients then entered a double-blind study. Phosphorus binders were stopped for 1 week. Calcium acetate (at a dose established in a prior study) or placebo was then administered for 2 weeks. Next, patients were crossed to the opposite regimen for 2 weeks. Initial phosphorus was 2.36 mmol/L (7.3 mg/100 mL) and calcium 2.22 mmol/L (8.9 mg/100 mL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic value of serum prostate-specific antigen in hemodialysis patients

BACKGROUND: The value of serum prostate-specific antigen (PSA) screening was examined to detect prostate cancer in men receiving hemodialysis. METHODS: Forty-one male patients age 60-95 (median age, 70 years) receiving hemodialysis were investigated for PSA levels. We set the cut-off point at 4 ng/mL (the usual reference range). Digital rectal examination (DRE) and transrectal ultrasonography (TRUS) of the prostate were performed in patients whose PSA was more than 4 ng/mL and/or who expected further examination of the prostate. When prostate cancer was suspected, biopsy of the prostate was performed. In patients with prostate cancer, magnetic resonance imaging, computed tomography and bone scintigraphy were performed to diagnose the clinical stage. RESULTS: The mean serum level of PSA was 2.10 +/- 0.49 ng/mL. In this screening study, four of 41 men required further examinations for prostate cancer. Two of four refused further examinations. The other two were diagnosed with prostate cancer. The incidence of prostate cancer was at least 5% in our hemodialysis patients. One man, whose clinical stage was T2aN0M0, was treated with radical retropubic prostatectomy. Another man, whose clinical stage was T2bN0M0, was treated with luteinizing hormone-releasing hormone analogue. CONCLUSION: In our preliminary study, prostate cancer screening with PSA was useful for the early detection of prostate cancer in hemodialysis patients. If possible, DRE and TRUS should be performed in conjunction with PSA tests.     

Effects of hemodialysis membrane on serum lipid profile of maintenance hemodialysis patients

Atherosclerosis and lipid abnormalities are still insuperable complications for maintenance hemodialysis patients. We observed the serum lipid profile of 27 maintenance hemodialysis patients (M : F; 20 : 7, age; 54.9 +/- 6.2 y. o., hemodialysis duration; 10.8 +/- 4.9 years, body weight; 53.6 +/- 4.4 kg) using a low flux cellulose membrane, cellulose (1.5 m2), a vitamin-E-modified dialysis membrane, CL-15E (CL- 15E 1.5 m2, Terumo), and polysulfon, PS (PS-1.3UW 1.3 m2, Fresenius) dialysers. Each membrane dialyzer was used for 3 months. The blood flow rate was 200 ml/min, and hemodialysis time, 4 hours. When the dialyzers were replaced, fasting blood was collected at the beginning of hemodialysis and serum lipid parameters were measured. Seven additional maintenance hemodialysis patients were selected and TC, TG, HDL-C were measured as controls, because their dialyzers (low flux cellulose 1.5 m2) and hemodialysis conditions were not changed during the study. TC was decreased by PS and there were significant differences between cellulose and PS, and between CL-15E and PS. However, these changes were conducted within the normal range of TC. TG was not significantly changed during the study. HDL-C was decreased by CL-15E and PS as well as TC. There were significant differences in HDL-C between cellulose and CL-15E, and between cellulose and PS. Apo B, Apo B/A-I were decreased by PS and there were significant differences between cellulose and PS, respectively, LP(a) was not changed during the study. RLP-C (Cellulose vs. PS, CL-15E vs. PS), VLDL-C (Cellulose vs PS), and LDL-C (cellulose vs. PS, CL-15E vs. PS) were significantly decreased between membranes, respectively. Although the precise mechanism is yet unknown, the uptake of LDL and remnant into receptors of the liver might be improved by PS hemodialysis. In conclusion, these data suggest that PS decreased the serum levels of the lipid profile in maintenance hemodialysis patients and may be effective in improving their lipid abnormality.     

Studies of serum bone Al-P isoenzyme and serum osteocalcin in patients on maintenance hemodialysis

This report describes an investigation of 128 patients on maintenance hemodialysis. Their serum bone Al-P isoenzyme (Al-P III) values were measured by the Rosalki method, and simultaneous estimations were made of their serum osteocalcin levels as a diagnostic indicator of renal osteodystrophy (ROD). ROD was evaluated clinically from Jensen's criteria, based on a four-stage classification of the radiographic evidence for subperiosteal resorption: no change (stage 0), minor change (stage I), and definite change (stages IIa and IIb). The serum Al-P III levels in the stage IIa and IIb patients showed significantly elevated values (p less than 0.01), i.e., 4.98 +/- 6.23 and 20.51 +/- 13.46 KAU, respectively. In contrast, their serum osteocalcin levels were not appreciably different. Patients with elevated N-PTH values of 0.30 ng/ml or more were found to have serum Al-P III levels of 20 KAU or more, and all of these patients were categorized under the stage IIb classification. It is concluded therefore that in chronic renal failure patients on hemodialysis, measurements of the serum Al-P III are highly useful for diagnosing ROD, and may also be considered as a critical parameter for assessing the indication for parathyroidectomy (PTX).     

Increased cortisol metabolites and reduced activity of 11beta-hydroxysteroid dehydrogenase in patients on hemodialysis

BACKGROUND: Patients with renal failure have symptoms assumed to be attributable to the accumulation of toxic endo- or xenobiotics. Most of these molecules, especially those with a molecular weight>300 D, have not been identified. In addition to excretion, the kidney is involved in some defined metabolic processes. In the cortical collecting duct, the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) interconverts cortisol (F) and cortisone (E), and the metabolites of these glucocorticoids, tetrahydrocortisol (THF), 5alpha-tetrahydrocortisol (5alpha-THF) and tetrahydrocortisone (THE), are excreted in urine. We hypothesized that first, these metabolites accumulate and second, their concentration pattern changes in patients on hemodialysis. METHODS: THF, 5alpha-THF, THE, F and E were measured in plasma of 63 patients on dialysis and in 34 healthy controls by gas-chromatography-mass spectrometry (GC/MS). In 11 patients, the metabolite clearance was determined during high flux hemodialysis by using a population pharmacokinetic approach. RESULTS: Mean plasma concentrations of THF, 5alpha-THF and THE were more than five times higher and those of E lower in patients than in controls. The ratios of (THF + 5alpha-THF)/THE and F/E were increased in patients, indicating a reduced activity of 11beta-HSD2. Intradialytic clearances were between 120 and 300 mL/min and not sufficient to normalize the steroid concentrations. CONCLUSION: Patients on hemodialysis exhibit pronounced increases in THF, 5alpha-THF and THE concentrations in plasma with insufficient removal during dialysis. Due to a reduced 11beta-HSD2 activity, an abnormal pattern of the concentrations of these cortisol and cortisone metabolites is observed. Since many signs and symptoms in uremic patients resemble those observed in subjects with glucocorticoid excess, the clinical relevance of the high concentrations of these glucocorticoid metabolites deserves further investigation.     

Center-specific variations of thyroid hormone serum levels in hemodialysis patients

Thyroid hormone (free and total thyroxine, total 3,5,3'- and 3,3'5'-triiodothyronine, thyroxine-binding globulin, thyrotropin) serum concentrations were measured in 107 uremic patients of 4 hemodialysis centers, in order to study the prevalence of hypothyroidism in hemodialysis patients. In accordance with the clinical impression there was no laboratory evidence of thyroid dysfunction. In spite of the fact that all patients had the expected low-T3 syndrome, there were highly significant differences between the mean thyroid hormone concentrations of the 4 different centers. The center with the highest thyroid hormone levels (all normal except for borderline low 3,5,3'-triiodothyronine) also had the lowest urea levels, indicating the relatively best metabolic control. One center had significantly lower hormone levels than the other 3 centers (all hormones except free thyroxine were below normal) with urea levels that did not differ significantly from one of these centers. A retrospective analysis of patients and of the techniques of dialysis of 3 centers excluded factors like heparin or the length of time on dialysis to be the reason for the low values of this center. Finally, only the significantly higher proportion of unsuccessfully transplanted patients and some technical differences (lack of water treatment, regenerated cellulose as dialyser membrane, and low magnesium content in the dialysate) unique for this center remained as possible factors that may speculatively explain the observed low thyroid hormone values.(ABSTRACT TRUNCATED AT 250 WORDS)     

维持性血液透析患者氧化应激水平及其相关因素的分析

目的探讨维持性血液透析患者氧化应激水平及其相关影响因素。方法测定30例维持性血液透析患者血清丙二醛（MDA）和SOD水平，并与正常人比较，分析C反应蛋白、动脉粥样硬化与氧化应激的关系以及血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂、不同的血液净化方式对维持性血液透析患者氧化应激水平的影响。结果维持性血液透析患者氧化应激水平明显增高，与C反应蛋白、动脉粥样硬化的形成明显相关，使用血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂以及进行血液透析滤过治疗的透析患者血清MDA水平明显降低（P〈0．01）。结论维持性血液透析患者氧化应激水平较正常人明显升高，有动脉硬化并发症者升高更明显。血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂、血液透析滤过治疗能减轻维持性血液透析患者的氧化应激水平。     

血清巨噬细胞集落刺激因子与维持性血液透析患者骨密度的关系

目的通过对维持性血液透析患者血清中巨噬细胞集落刺激因子(macrophage colonystimulating factor,M-CSF)水平及骨密度(bone mineral density,BMD)的检测,探讨血清M CSF水平与维持性血液透析患者BMD的关系,以及影响BMD的相关因素。方法选择华中科技大学同济医学院附属同济医院血液透析中心维持性血液透析患者50例为观察组,另选择健康体检者8例为健康对照组。收集入选者的临床资料包括性别、年龄、血红蛋白、血钾、血磷、血钙、甲状旁腺素、尿素氮、尿酸和血肌酐的情况。用ELISA法检测2组患者透析前血清M-CSF浓度。用骨密度仪检测所有患者BMD,结果以T-Score表示。Spearman分析BMD、M-CSF与各临床指标的相关性。血液透析患者分别按照BMD值分为骨质疏松组、骨量减少组和骨密度正常组,分析不同组别中BMD值与M-CSF的相关性。结果①观察组患者M-CSF水平与健康对照组比较明显升高(P0.0001);Spearman相关性分析发现BMD与年龄呈负相关(r=-0.2756,P=0.0264),与性别(r=0.3701,P=0.0041)呈正相关,女性患者骨质疏松的发生率更高。②观察组M-CSF与BMD进行spearman相关性分析,发现按照T-Score分组后,骨质疏松组M-CSF与BMD呈负相关(r=-0.3842,P=0.0522);骨密度正常组(r=-0.1324,P=0.3490)和骨量减少组(r=-0.029 99,P=0.4501)M-CSF与BMD无明显相关。结论 M-CSF与BMD呈负相关,随着血清M-CSF水平的升高,骨密度逐渐下降,骨质疏松发生率增加。维持性血液透析患者血清M-CSF水平升高与患者骨质疏松的发生及进展有关。     

维持性血液透析患者血清脂联素与动脉粥样硬化的相关性分析

目的探讨维持性血液透析患者血清脂联素水平与动脉粥样硬化的相关性。方法将30例维持性血液透析患者设为透析组,10名相匹配的健康体检者设为对照组,测定血清脂联素水平,同时测定相应的生化指标及颈总动脉内膜中层厚度,并根据颈动脉内膜厚度,将维持性血液透析患者分为颈动脉正常组和颈动脉硬化组。结果维持性血液透析患者血清脂联素水平明显高于对照组（P〈0．05）,与颈动脉内膜中层厚度呈显著负相关（r=－0．378,P〈0．05）;而颈动脉硬化组血清脂联素水平低于颈动脉正常组（P〈0．05）。结论维持性血液透析患者血清脂联素明显高于正常人,其浓度与动脉硬化程度呈负相关,对其更深一步的研究有助于对维持性血液透析患者动脉硬化的发生提供更好、更敏感的检测方法。     

Quality of life and its correlates in ambulatory hemodialysis patients

BACKGROUND: In hemodialysis patients, quality of life (QOL) may vary across a range of individual conditions and social environments. In this study, we focused on ambulatory hemodialysis patients, examining their QOL compared with that of age-matched controls. Correlates of QOL in ambulatory hemodialysis patients were also examined. METHODS: QOL was evaluated by WHOQOL in ambulatory hemodialysis patients and age-matched controls. Correlations of QOL with age, sex, body mass index (BMI), functional performance, physical activity, cognitive function, psychiatric disorders, diabetes status, comorbidities, duration of dialysis therapy, adequacy of dialysis, biochemical variables and nutritional status were also examined in ambulatory hemodialysis patients. RESULTS: In WHOQOL, we found decreased psychological domain scores (19.8 vs. 21.6, p=0.012) and overall QOL (89.0 vs. 94.3, p=0.035) for ambulatory hemodialysis patients compared with age-matched controls, especially in the items: enjoying life (p=0.032), feeling life has meaning (p=0.023), having opportunity to take leisure time (p=0.003) and being satisfied with sexual life (p=0.044). Patients with male sex, BMI >24 and duration of dialysis shorter than 5 years had lower overall QOL than controls. Male dialysis patients also had lower QOL than female patients. As for correlates of QOL in ambulatory hemodialysis patients, age, BMI and psychiatric disorders were negatively correlated. By contrast, premorbid and current satisfaction with personal health were positively correlated. CONCLUSIONS: QOL in ambulatory hemodialysis patients was lower than in age-matched controls. QOL in ambulatory hemodialysis patients was positively correlated with personal health satisfaction and negatively correlated with age, BMI and psychiatric disorders.     

维持性血液透析患者血尿酸与心血管疾病的关系

本研究旨在研究维持性血液透析（MHD）患者血尿酸（UA）与心血管疾病的关系，探讨血尿酸对心血管系统影响的机制，从而减少心血管疾病的发生率，改善MHD患者的生活质量。     

Impact of serum albumin and body-mass index on survival in hemodialysis patients

A low body mass index (BMI) and serum albumin are associated with increased risk of mortality in patients with chronic kidney disease (CKD). The purpose of this study was to evaluate BMI and serum albumin as predictors of all-cause and cardiovascular (CV) mortality in hemodialysed (HD) patients. We describe the results of a five-year retrospective observational study with 187 HD patients (54.9 ± 15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor Clinic in Rio de Janeiro, Brazil. The influence of serum albumin levels and BMI (determined every three months) over all-cause mortality was examined using a Cox model, while the influence of the same factors over CV mortality among all-cause mortality was modeled through a logistic regression. During the five years, 26.7% of the patients died, 62% of which due to CV disease (CVD). Analysis by the Cox model showed that low serum albumin and low BMI were significant predictors of mortality. Patients with higher BMI had a lower hazard of death for all-cause mortality (hazard ratio [HR] = 0.92; P = 0.035) and a 1 g/l increase in serum albumin was associated with significantly lower hazard of death (hazard ratio = 0.9679; P < 0.001). The highest BMI value (>30 kg/m²) was significantly associated with an increase of odds of CV mortality (odds ratio = 1.22, P = 0.03). We confirm here in a Brazilian cohort of hemodialysis patients that both low BMI (<19 kg/m²) and hypoalbuminemia are strong predictors of death.     

Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients

AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.