Continuous Ambulatory Peritoneal Dialysis Subjects Research Articles

High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype invivo and invitro.

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long-term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD-related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme-linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14- and CCr7-positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14- and CD206-positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high-glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration-dependent and time-dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor β1 in the supernatant increased in a glucose concentration-dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD-related fibrosis.

Dialysis modality is independently associated with circulating endothelial progenitor cells in end-stage renal disease patients

Numbers of endothelial progenitor cells (EPC) have been shown to be decreased in subjects with end-stage renal disease (ESRD). It is not clear, however, whether dialysis modality affects circulating EPCs in ESRD subjects. We examined the number of circulating EPCs in 67 continuous ambulatory peritoneal dialysis (CAPD) patients and age- and gender-matched 142 haemodialysis (HD) patients, and 78 subjects without chronic kidney disease. Arterial stiffness was analysed as pulse-wave velocity (PWV) for these patients, and their mutual relationship with circulating EPCs was examined. EPCs were measured as CD34(+) CD133(+) CD45(low) VEGFR2(+) cells determined by flow cytometry. The EPC numbers exhibited a strong correlation (R(2) = 0.866) with endothelial-colony forming units on culture assay. The levels of EPCs in HD or CAPD subjects were significantly lower than those in control subjects. Among ESRD subjects, the levels of EPC were significantly higher in CAPD subjects than those in HD subjects. In ESRD subjects, PWV levels tended to be associated with EPCs (Rs = -0.131, P = 0.058). However, the significant relationship between dialysis modality and circulating EPCs was independent of the levels of PWV. The association of circulating EPCs with dialysis modality was significant even after adjusting for other potential confounders, including age, gender, blood pressure, history of cardiovascular diseases, presence of diabetes, blood haemoglobin level and treatments with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or statin. CAPD treatment could be a positive regulator of number of circulating EPCs in subjects with ESRD, with the relationship independent of the status of arteriosclerosis.

Peritoneal transport characteristics and dwelling time significantly impact ghrelin clearance in peritoneal dialysis patients

Plasma ghrelin exerts widespread bioactivities. Although it is effectively removed from the blood by a single course of haemodialysis, peritoneal clearance of ghrelin is uncertain. Our study aimed to determine (i) whether there is a correlation between plasma ghrelin levels and characteristics of peritoneal ghrelin clearance, and (ii) whether plasma ghrelin levels significantly impact markers of mortality or morbidity in continuous ambulatory peritoneal dialysis (CAPD) patients. We enrolled 50 qualified CAPD patients. Blood was drawn during the fasting state and 2 h post-prandially. Also during these periods, peritoneal effluents were collected for radioimmunoassay of total plasma ghrelin level and measurement of other parameters. Twenty-four hour ascites were collected for determination of ghrelin daily mass transfer. Peritoneal ghrelin clearance was positively correlated with the dialysate-peritoneal creatinine (D/P(Cr)) ratio. Fasting plasma ghrelin levels were inversely correlated with the peritoneal/plasma (D/P(ghrelin)) ratio (P = 0.045). Plasma ghrelin levels were negatively correlated with body mass index, waist-hip ratio, fasting insulin and triglyceride level, and positively correlated with lean body mass. Plasma ghrelin levels were positively correlated with left ventricular mass (LVM), left ventricular mass index and blood pressure. Peritoneal transporter characteristics may modulate plasma ghrelin levels in CAPD subjects. By contributing to the level of plasma ghrelin, dwelling time may have an impact on LVM and associated morbidity in CAPD patients.

The periodontal status of pre-dialysis chronic kidney disease and maintenance dialysis patients

Periodontitis contributes to generalized inflammation and development of systemic diseases, including atherosclerosis and cardiovascular disease. Its extent in maintenance haemodialysis (HD) patients is disputable and not known in continuous ambulatory peritoneal dialysis (CAPD) and pre-dialysis chronic kidney disease (CKD) patients. One hundred and six patients (35 on HD, mean age, 56 years; 33 on CAPD, mean age 51 years; and 38 pre-dialysis CKD stage 2-5, mean age 51 years) from north-eastern Poland were enrolled. Dialysis subjects were recruited from a cohort of 141 HD and 61 CAPD patients. Two control groups comprised 26 generally healthy individuals with advanced periodontitis requiring specialized treatment, and 30 subjects from general population. Gingival index (GI), papillary bleeding index (PBI), plaque index (PI), loss of clinical attachment level (CAL) and community periodontal index of treatment needs (CPITN) were determined according to WHO recommendations. Average values of the indices in HD, CAPD, pre-dialysis CKD, advanced periodontitis and general population subjects were as follows: GI-1.37, 0.95, 1, 2 and 1; PBI-1.45, 0, 0, 2.20 and 1; PI-2.05, 1.59, 1, 2 and 1; and CAL loss-5.11, 3.47, 2.50, 4.68 and 1.40 mm, respectively. CPITN, analysed separately as community periodontal index and periodontal treatment needs, further indicated a high severity of periodontitis in all renal failure groups as compared with general population subjects. The disease was most advanced in maintenance HD patients-comparable to the full-symptomatic form of periodontitis; then it was successively diminished in CAPD and pre-dialysis CKD subjects. Periodontal disease is prevalent, severe and under recognized in renal failure patients. Prophylaxis and early dental treatment should be intensified in these subjects, and may be of interdisciplinary importance.

The Influence of Dialytic Modality on Arterial Stiffness, Pulse Wave Reflections, and Vasomotor Function

Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (Alx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and Alx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic Alx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in Alx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 +/- 1.09 m/ second in CAPD patients, significantly higher (p < 0.05) compared to HD subjects (7.19 +/- 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 +/- 1.62 m/s) and essential hypertensive controls (6.34 +/- 1.32 m/s), p < 0.05. The Alx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in Alx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.

Anthropometric and growth assessment of children receiving renal replacement therapy in Malaysia

Objective: To report on the anthropometric and growth status of children receiving renal replacement therapy (RRT) in Malaysia. Design: Cross-sectional study with some retrospective elements. Setting: Outpatients' clinics in a major referral hospital in Malaysia. Patients: Fifteen renal transplants (mean age, 13.3 ± 2.8 years) and 35 continuous ambulatory peritoneal dialysis (CAPD) patients (mean age, 12.6 ± 3.0 years) participated. The RRT period ranged between 3 months to 6 years for both groups. Intervention: None. Main Outcome Measures: Body mass index (BMI), percent body fat (% BF), triceps skinfold (TSF), mid upper-arm circumference (MUAC), arm muscle area (AMA), and z scores for height and weight. Results: BMI for age indicated 7% of transplant subjects (TS) versus 40% of CAPD subjects were below the 5th percentile, whereas only 7% of TS were above the 95th percentile. % BF was higher for TS compared with the CAPD group for both sexes (boys, 19.5% and girls, 29.8% v boys, 12.4% and girls, 21.5%). Despite higher percentiles for TSF, transplant subjects still showed depleted muscle mass based on MUAC and AMA. z scores for height showed 93% of transplant subjects and 62% of CAPD subjects below −2 standard deviation (SD), whereas for weight these were 27% and 54%, respectively. Sixty-four percent of TS experienced catch-up growth for height and 86% for weight. These percentages were approximately halved for the CAPD group (32% and 43%, respectively). Conclusion: Patterns of growth and body composition appear distinctly different with the different RRT modalities. Serial anthropometric evaluation appears vital in pre- and post-RRT monitoring in pediatric renal populations. © 2002 by the National Kidney Foundation, Inc.

Insulin-Like Growth Factor System Components in Relation to Erythropoietin Therapy and Bone Metabolism in Dialyzed Patients and Kidney Transplant Recipients

Insulin-like growth factor (IGF) system components appear to be the most important regulators of bone cell function. On the other hand, IGF-1 is shown to be an important regulator for erythropoiesis. The aim of the study was to examine the relationships between IGF system, requirements of erythropoietin, endogeneous erythropoietin levels, bone metabolism assesed by biochemical markers, markers of nutrition such as cholesterol and albumin in recombinant human erythropoietin (rHuEPO)-treated patients maintained on chronic hemodialyses or peritoneal dialyses as well as in kidney transplant recipients. The studies were performed on 79 chronically hemodialyzed patients; 28 of them did not receive rHuEPO, 51 subjects received rHuEPO, 34 patients on continuous ambulatory peritoneal dialysis (CAPD), 16 of them did not receive rHuEPO, 18 were given rHuEPO and 46 kidney allograft recipients. Endogeneous erythropoietin concentration, bone-specific alkaline phosphatase and serum CrossLaps were assayed by ELISA. Intact PTH, osteocalcin, 1,25-(OH)₂ D₃, 25-OH D₃, IGF-1, procollagen type I carboxy-terminal extension peptide (PICP) and procollagen type I cross-linked carboxy-terminal telopeptide (ICTP) were studied by RIA, whereas IGFBP-1 and IGFBP-3 concentrations were assayed by IRMA. We found a significantly higher IGF-1 and IGFBP-3 in rHuEPO-treated HD patients when compared to CAPD subjects given rHuEPO as well as to hemodialysis (HD) patients not treated with rHuEPO. IGF-1 was significantly higher in kidney transplant recipients when compared to dialyzed patients without rHuEPO therapy. IGFBP-1 was similar in all groups of patients (including kidney transplant recipients) studied. In CAPD patients not given rHuEPO concentrations of ICTP and PICP were significantly lower when compared to rHuEPO-treated CAPD subjects and HD patients not receiving rHuEPO therapy. Serum CrossLaps in CAPD patients treated with rHuEPO were significantly higher when compared to CAPD subjects without rHuEPO treatment and to kidney transplant recipients. In rHuEPO-treated CAPD subjects IGF-1 and IGFBP-1 correlated positively with serum CrossLaps (r = 0.61, p < 0.05 and r = 0.64, p < 0.05, respectively), whereas in hemodialyzed patients without rHuEPO a significant negative correlation between IGFBP-3 and serum CrossLaps was found (r = –0.69, p < 0.001) as well as between IGFBP-3 and aluminium (r = 0.51, p < 0.05), IGF-1 and ICTP (r = –0.43, p < 0.05). In conclusion, our data indicate a probable functional relationship between IGF system components, erythropoietin treatment in dialyzed patients and bone metabolism in renal replacement therapy in a form of hemodialyses, peritoneal dialyses and kidney transplantation. Dialyzed patients exhibit more pronounced renal osteodystrophy than kidney allograft recipients. IGF system components are influenced by erythropoietin therapy, but are not related to serum erythropoietin levels and rHuEPO requirements.

The relation between nutrition indices and age in patients on continuous ambulatory peritoneal dialysis receiving similar small solute clearances.

To analyze the effect of age on nutrition indices in subjects on the same continuous ambulatory peritoneal dialysis (CAPD) schedule. We analyzed 613 sets of clearance values and nutrition indices in 302 CAPD patients. Small solute clearances included urea clearance (Kt/Vurea) and creatinine clearance (Ccr). Nutrition indices included body mass index (BMI), serum albumin, urea and creatinine, 24-h urea nitrogen and creatinine excretion in urine plus dialysate, protein nitrogen appearance (PNA), PNA normalized by standard weight (nPNA), lean body mass (LBM) computed by creatinine kinetics, and LBM/Weight. CAPD subjects were classified in 4 age quartiles (Q): Group Q1, age 33.7 +/- 7.6 years, N = 149; group Q2, age 49.5 +/- 3.8 years, N = 158; group Q3, age 61.5 +/- 2.6 years, N = 154; and group Q4, age 72.1 +/- 5.4 years, N = 152. Group comparison was done by one-way ANOVA or chi-square. Predictors of low nutritional parameters were identified by logistic regression. Selected variables were compared by linear regression. Mean Kt/Vurea and Ccr were above the current adequacy standards and did not differ between the age quartiles. In contrast, older quartiles had, in general, lower nutrition indices than younger quartiles. However, the youngest quartile had the lowest BMI. By logistic regression, young age was a predictor of low BMI, while advanced age was a predictor of low creatinine and urea nitrogen excretion, low nPNA, and low LBM/Weight. The regressions of nPNA on Kt/Vurea differed between the age quartiles. By these regressions, the youngest quartile had higher nPNA values for the same Kt/Vurea than the oldest quartile in the clinically relevant range of Kt/Vurea and nPNA values. Nutrition indices are worse in older than in younger CAPD patients with the same small solute clearances. Nutrition of CAPD patients is adversely affected by age and requires special attention in the older age group.

Normalization of Clearances in Peritoneal Dialysis Using a Formula for Body Water Derived from an End-Stage Renal Disease Population

To compare body water (V) estimates from the Chertow formula (Vc), which was derived in an end-stage renal disease population, to V estimates from the Watson formulas (Vw) in continuous ambulatory peritoneal dialysis (CAPD) patients. To identify CAPD patients in whom Vc is preferred to Vw for clearance studies. Retrospective analysis of clearance studies. Dialysis units of four academic medical centers. 302 subjects on CAPD. 613 clearance studies by standard methods. Comparisons between Vc and Vw, and between urea clearance normalized by Vc [(KtVc)ur] and Vw [(Kt/Vw)ur]. Vc exceeded Vw by 3.5 +/- 1.6 L (p < 0.001), or 9.6% on average. This degree of overestimation of Vw is in the range of body water estimates found in CAPD subjects with severe volume overload (> 5% of body weight) in previous studies. Total (Kt/Nw)ur exceeded total (Kt/Vc)ur by 8.6%. By linear regression, Vc = -0.589 + (1.112 x Vw), r = 0.983. Vw exceeded Vc in only 12 studies. Young age, short height, low body weight, and low prevalence of diabetes characterized the studies with Vw > Vc. Total (Kt/Vw)ur was adequate (> or = 2.0 weekly) in 276 studies. Among these, 74 studies had inadequate total (Kt/Vc)ur (< 2.0 weekly). By logistic regression, the predictors of inadequate (Kt/Vc)ur, when (Kt/Vw)ur was adequate, included the presence of diabetes, great height, and long duration of CAPD. Vc provides estimates of body water exceeding those provided by Vw in a great majority of CAPD patients. Consequently, approximately 25% of the clearance studies that are adequate when Vw is used as the normalizing parameter may be inadequate when Vc is used. Vc may provide a more appropriate estimate of body water than Vw in CAPD patients with volume overload.

Effects of Insulin and Amino Acids on Glucose and Leucine Metabolism in CAPD Patients

This study investigates the basal and insulin-stimulated glucose metabolism, substrate utilization, and protein turnover in eight patients maintained on continuous ambulatory peritoneal dialysis (CAPD) (mean age 39+/-5 yr, body mass index [BMI] 108+/-6) and 14 control subjects (mean age 33+/-4 yr, BMI 103+/-3). Euglycemic insulin clamp studies (180 min) were performed in combination with continuous indirect calorimetry and 1-14C leucine infusion (study I). Postabsorptive glucose oxidation was higher (1.75+/-0.18 versus 1.42+/-0.14 mg/kg per min) and lipid oxidation was lower (0.43+/-0.09 versus 0.61+/-0.12 mg/kg per min) in CAPD patients than in control subjects (P<0.05 versus control subjects). During the last 60 min of euglycemic hyperinsulinemia, the total rate of glucose metabolism was similar in CAPD and control subjects (6.33+/-0.51 versus 6.54+/-0.62 mg/kg per min). Both insulin-stimulated glucose oxidation (2.53+/-0.27 versus 2.64+/-0.37 mg/kg per min) and glucose storage (3.70+/-0.48 versus 3.90+/-0.58 mg/kg per min) were similar in CAPD and control subjects. Basal leucine flux (an index of endogenous proteolysis) was significantly lower in CAPD patients than in control subjects (1.21+/-0.15 versus 1.65+/-0.07 micromol/kg per min). Leucine oxidation (0.13+/-0.02 versus 0.26+/-0.02 micromol/kg per min) and nonoxidative leucine disposal (an index of protein synthesis) (1.09+/-0.16 versus 1.35+/-0.05 micromol/kg per min) were also reduced in CAPD compared with control subjects (P<0.01 versus control subjects). In response to insulin (study I), endogenous leucine flux decreased to 0.83+/-0.08 and 1.05+/-0.05 micromol/kg per min in CAPD and control subjects, respectively (all P<0.01 versus basal). Leucine oxidation declined to 0.06+/-0.01 and to 0.19+/-0.02 micromol/kg per min in CAPD and control subjects, respectively (P<0.01 versus basal). A second insulin clamp was performed in combination with an intravenous amino acid infusion (study II). During insulin plus amino acid administration, nonoxidative leucine disposal rose to 1.23+/-0.17 and 1.42+/-0.09 micromol/kg per min in CAPD and control subjects, respectively (both P<0.05 versus basal, P = NS versus control subjects), and leucine balance, an index of the net amino acid flux into protein, become positive in both groups (0.30+/-0.05 versus 0.40+/-0.07 micromol/kg per min in CAPD and control subjects, respectively) (both P<0.01 versus basal, P = NS versus control subjects). In summary, in CAPD patients: (1) basal glucose oxidation is increased; (2) basal lipid oxidation is decreased; (3) insulin-mediated glucose oxidation and storage are normal; (4) basal leucine flux is reduced; (5) the antiproteolitic action of insulin is normal; and (6) the anabolic response to insulin plus amino acid administration is normal. Uremic patients maintained on CAPD treatment show a preferential utilization of glucose as postabsorptive energy substrate; however, their anabolic response to substrate administration and the sensitivity to insulin are normal.

Leptin elimination in hyperleptinaemic peritoneal dialysis patients.

Elevated plasma concentrations of leptin, a hormone thought to regulate body composition by influencing food intake/metabolic rate, are prevalent in renal failure patients. The mechanism for these increases is not known, but evidence suggests that simple accumulation due to decreased elimination is insufficient explanation. We studied the incidence of hyperleptinaemia in 28 end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), compared with body-mass-index-and sex-matched controls. Results were separated by gender because women have higher leptin concentrations than men. Excretion of leptin and other substances in dialysis fluid was also studied. Hyperleptinaemia was prevalent in women CAPD subjects, but not in men. Plasma leptin concentrations correlated strongly with the daily excretion of leptin in dialysis fluid. Clearance of leptin in dialysis fluid was greater in men than women CAPD subjects. Single regression analysis found that fasting insulin, glucose content of dialysis fluid, plasma albumin, C-reactive protein, erythropoietin dose, urinary creatinine clearance and plasma beta2-microglobulin were not determinants of plasma leptin concentrations. Stepwise forward multiple regression, examining the dependence of plasma leptin on body mass index, renal creatinine clearance, plasma albumin, daily dialysis fluid glucose load, daily leptin in dialysis fluid, erythropoietin dose and plasma C-reactive protein found only erythropoietin dose as a consistent negative predictor of plasma leptin concentrations. The results suggest that hyperleptinaemia of CAPD was due to predisposing loss of renal elimination capacity combined with increased production due to obesity (more prevalent in women subjects of this study) and potentially female gender.

Effects of Oral Glucose on Intermediary Metabolism in Continuous Ambulatory Peritoneal Dialysis Patients versus Healthy Subjects

To explore the mechanisms and metabolic consequences of the insulin resistance of patients treated by continuous ambulatory peritoneal dialysis (CAPD). CAPD patients and healthy subjects ingested a similar mean oral glucose load per kilogram of fat-free mass (FFM) [1.20+/-0.03 g/(kg FFM) vs 1.20+/-0.06 g/(kg FFM); CAPD vs healthy subjects]. Substrate oxidation was monitored over 6 hours using indirect calorimetry. Peritoneal dialysis unit of a tertiary-care institutional center. Glycemia, insulinemia, substrate oxidation. Six CAPD patients (68+/-5 yr) and 6 healthy subjects (24+/-1 yr). The CAPD patients had similar body mass index (21.4+/-1.3 vs 22.9+/-1.1 kg/m2), a higher percent fat (25.8%+/-3.7% vs 16%+/-2.2%; p < 0.05), and a lower FFM (42.2+/-2.2 kg vs 56.5+/-2.6 kg; p < 0.01) than healthy subjects. The CAPD patients displayed a higher glycemic and insulinemic responses to glucose than did healthy subjects (p < 0.05), but similar glucose oxidation and storage. Lipid oxidation and plasma nonesterified fatty acids were not increased in CAPD patients versus healthy subjects, in spite of a higher adiposity. Fat oxidation was related to fat mass in CAPD patients (r2 = 0.77, p < 0.05) but not in healthy subjects (r2 = 0.05). CAPD patients display an insulin-resistance not explained by an increased lipid oxidation. The maintenance of intracellular glucose utilization at the expense of higher glycemic and insulinemic responses suggests a defective glucose transport.

Influence of variation at the apolipoprotein E locus on lipid and lipoprotein levels in CAPD patients.

Variation at the apolipoprotein E (apo E) locus influence lipid and lipoprotein levels in the normal population, and is associated with premature coronary artery disease. Patients with end-stage kidney disease or undergoing dialysis treatment are particularly prone to develop accelerated atherosclerosis. To evaluate the influence of genetic variation at the apo E locus, apo E genotypes and serum lipid and lipoprotein levels were measured in 51 subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). The distribution of apo E phenotypes and apo E allelic frequency among the CAPD subjects (epsilon 2 0.049; epsilon 3 0.745: epsilon 4 0.206) corresponded to the healthy Swedish population. In the CAPD subjects, total serum and LDL cholesterol levels were high (6.7 +/- 1.5 mmol/l and 4.2 +/- 1.3 mmol/l respectively) and HDL cholesterol levels were low (1.2 +/- 0.5 mmol/l). When directly comparing the two major apo E groups. E 3/3 subjects (n = 30) and E4/3 and 4/4 subjects, epsilon 4-carriers, (n = 16), LDL cholesterol levels were significantly higher among epsilon 4-carriers (4.8 +/- 1.1 vs 4.0 +/- 1.2 mmol/l, P < 0.03), but total serum cholesterol levels was not higher among the epsilon 4-carriers (7.3 +/- 1.3 vs 6.5 +/- 1.5 mmol/l, P < 0.08). Serum triglycerides or HDL cholesterol levels did not differ significantly between epsilon 3-homozygotes and epsilon 4-carriers. The results demonstrate a strong effect of variation of the apo E locus on LDL cholesterol levels in CAPD subjects, suggesting that epsilon 4-carriers may be more susceptible to accelerated development of atherosclerosis in this condition.

Increased serum pancreatic enzymes in uremia: relation with treatment modality and pancreatic involvement.

Increased levels of pancreatic enzymes have been reported in patients with renal insufficiency and ascribed either to impaired urinary excretion or, in a few studies, to the presence of pancreatic damage. In the present study serum total amylase, pancreatic amylase, and lipase were evaluated in 63 patients with chronic renal insufficiency (CRF), in 98 patients on hemodialysis (HD), in 28 patients on continuous ambulatory peritoneal dialysis (CAPD), in 23 patients with renal transplantation (RT), and in 34 normal volunteers (C). Serum parathyroid hormone and triglyceride levels were also measured in the majority of patients. Ultrasound examination of the pancreas was performed in a select number of cases. Mean values of pancreatic enzymes were significantly higher in all the study groups in comparison with controls, but values exceeding three times the upper normal limit were detected only in HD patients, who also showed amylase and lipase levels significantly highly than those of CAPD and CRF subjects. Negligible amounts of pancreatic enzymes were detected in peritoneal fluid of CAPD patients. Significant correlations were found with serum creatinine in CRF, with parathyroid hormone in HD and CAPD, and with duration of treatment in HD. No pancreatic abnormalities were detected by ultrasound. In conclusion, very high levels of pancreatic enzymes are seen mainly in HD patients and might be related more to the metabolic derangement of long-term dialysis treatment than to the occurrence of acute pancreatic damage.

Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes.

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.

Impact of Current Dialysis Techniques on Copper Status and Acute Phase Response in Females

The impact of current dialysis techniques on indicators of copper status and acute phase response was investigated in this research study to determine whether differences occurred between females dialysed using maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).Methodology: Female subjects with end stage renal disease for less than 5 years receiving either maintenance HD, or CAPD, and healthy female controls consented to participate. HD subjects (n = 11; 5 African-American and 6 Caucasian) ranged in age from 28–77 yr (48.0 ± 18.2 yr). HD subjects were dialyzed using cellulose ester (n=3), cellulose acetate (n=4), and polysulfone (n=4) dialyzers. CAPD subjects (n=l1; 11 Caucasian) ranged from 24–70 yr (53.5 ± 13.2 yr). Control subjects (n=11; 11 Caucasian) ranged in age from 24–64 yr (40.1 ± 12.5 yr). Plasma albumin, plasma creatinine, plasma glucose, and blood urea nitrogen were assayed in controls to confirm normal health status. Plasma was collected in trace element grade tubes to obtain fasting plasma copper (Cu), plasma ceruloplasmin activity (CpA), plasma ceruloplasmin concentration (CpC), ceruloplasmin activity to concentration (CpA:CpC), erythrocyte superoxide dismutase with extracted protein (RBCSOD), and plasma interleukin-6 (IL-6). Indicators of copper status and acute phase response were assayed as follows: Cu using atomic absorption spectrophotometry; CpA and RBCSOD using spectrophotometry, CpC using radial immunodifiusion; and IL-6 using an enzyme-linked immunoabsorbent asssay.Statistical Analyses: All data was expressed as mean ± S.D. using the Statistical Analysis Software Program. ANOVA were calculated and considered statistically significant at P< 05.Maior findings: Plasma Cu (1.0 ± .3ng/mL) was significantly (P< 01; ANOVA) depressed in HD only. CpA was significantly (P<01) depressed in both HD (78.27 ± 22.09U/L) and CAPD (94.55 ± 43.39U/L). CpC (687 ± 254mg/L) was significantly (P<05) depressed in HD only. CpA: CpC was significantly depressed (P<01) in both HD (0.17 ± 44U/mg) and CAPD (0.14 ± .53U/mg). RBCSOD (1952.1 ± 980.3U/mg) was significantly (P<01) elevated in HD only. Plasma interleukin-6, an indicator of acute phase response, was significantly (P<.05) elevated in both HD (3.2 ± 4.3pg/mL) and CAPD (3.0 ± 3.1pg/mL). Comparisons between dialysis treatment groups revealed significantly (P<05) depressed CpC and RBCSOD concentrations in females receiving HD compared to those receiving CAPD.Conclusions: This study suggests that despite technical improvements in maintenance dialysis techniques indicators of copper status and acute phase response are abnormal in females undergoing either HD or CAPD. These findings further suggest fewer copper anomalies occur in females prescribed CAPD compared to HD.

Pharmacokinetics and ex vivo susceptibility of cefpodoxime proxetil in patients receiving continuous ambulatory peritoneal dialysis

Pharmacokinetics of cefpodoxime, an extended-spectrum cephalosporin, were determined for eight noninfected patients on continuous ambulatory peritoneal dialysis (CAPD) and eight healthy volunteers. Subjects were matched for sex, age (+/- 6 years), and body weight (+/- 10 kg, except for one pair) and received a single 200-mg (cefpodoxime equivalents) oral dose of the prodrug cefpodoxime proxetil in an open-label, paired-design fashion. Dialysate (CAPD group only), plasma, and urine samples were collected and assayed for cefpodoxime by a microbiologic method. In addition, mean bactericidal titers of the effluent dialysate against selected bacterial strains often associated with CAPD-related peritonitis were determined at 6 and 24 h after the dose. There was a significant difference (P < 0.05) in all pharmacokinetic parameters between healthy and CAPD subjects, except for lag time to absorption. The mean peak plasma cefpodoxime concentration of 1.88 +/- 0.6 micrograms/ml occurred at 2.44 +/- 0.5 h for healthy volunteers, while the peak concentration of 3.25 +/- 1.4 micrograms/ml occurred at 12.0 +/- 4.2 h for patients on CAPD. The average elimination half-life in CAPD patients was approximately 12 times greater than that seen in healthy volunteers. Peritoneal dialysis had a minimal effect on cefpodoxime clearance. In healthy volunteers, 24.2% +/- 13% of the dose was recovered from the urine, in contrast to only 5.59% +/- 6.9% for CAPD patients. The mean bactericidal titers for all CAPD patients, at 6 and 24 h, were mostly less than 1:2 and did not exceed 1:4 for any of the isolates. Because of the decreased renal clearance and negligible dialysate clearance of cefpodoxime, and delayed drug absorption, the dosage interval for cefpodoxime proxetil may need to be extended in CAPD patients.

Insulin binding and glycolytic activity in erythrocytes from dialyzed and nondialyzed uremic patients.

Insulin resistance in uremia has been attributed to impaired hormone-receptor binding or to postbinding defects. Oral glucose tolerance tests, insulin binding, and in vitro glycolytic activity were studied in purified red blood cells from normal control subjects (C) and from uremic patients belonging to three groups: nondialyzed (U), on chronic hemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD). Glucose intolerance and hyperinsulinemia were demonstrated in all groups of patients. Maximal specific binding of 125I-insulin to erythrocytes, kinetically derived receptor numbers per cell, and affinity constants for insulin binding did not differ between control and patient groups. No correlation was found between the degree of glucose intolerance and insulin binding parameters. Basal lactate production by erythrocytes incubated in vitro was significantly higher in U and HD patients than in C, whereas CAPD patients did not differ from C in this respect. Addition of 1 mM dibutyryl-cAMP and 0.5 mM isobutyl-methyl-xanthine during incubation of erythrocytes caused an increase in the rate of lactate production that was similar in magnitude in the U, HD and C groups, whereas cells from CAPD subjects showed a significantly larger absolute response to these compounds after 1 h of incubation. There was no evidence of impairment of glycolytic capacity in red blood cells from uremic patients. In addition, no correlation was found between the degree of glucose intolerance and basal or stimulated lactate production by erythrocytes. Our results obtained in human erythrocytes suggest that the insulin resistance observed in uremia does not involve a defect in hormone binding or in the intracellular capacity to utilize glucose through glycolysis.

Twenty-four hour hormonal and metabolic profiles in uraemic patients before and during treatment with continuous ambulatory peritoneal dialysis.

Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (+/- SEM) levels fell from 6.63 +/- 0.40 to 6.00 +/- 0.26 mmol/l (P less than 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 +/- 0.42 mmol/l before dialysis to 2.02 +/- 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose.

Serum thyroid hormone levels in patients on continuous ambulatory peritoneal dialysis and regular hemodialysis.

In vitro thyroid function tests were performed on clinically euthyroid patients undergoing regular hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). The mean serum total thyroxine (TT4) and total triiodothyronine (TT3) values measured before HD were significantly subnormal. Similarly, CAPD subjects had reduced TT3 concentrations with low normal TT4 levels. Free thyroxine measurements, estimated by two different methods were aberrant in CAPD patients. Low normal reverse triiodothyronine (rT3) values were found in HD, in contrast to high normal rT3 levels in CAPD. Thyroid stimulating hormone determinations were normal, corresponding with the euthyroid status in both patient groups.