Beta 2-microglobulin Clearance Research Articles

Effect of high throughput hemodialysis and hemoperfusion on clearance of beta 2-microglobulin in nephritis

Objective To investigate the clearance effect of high throughput hemodialysis and hemoperfusion on beta beta 2-microglobulin(β2-MG) in patients with nephritis. Methods From January 2015 to April 2018, 80 patients with nephritis admitted to our hospital were selected.According to different treatment methods, the patients were divided into experimental group and control group, with 40 patients in both groups.Patients in the control group were treated with high-throughput hemodialysis, while patients in the experimental group were treated with high-throughput hemodialysis and hemoperfusion. Results The levels of β2-MG, BUN and Cr in the experimental group were significantly lower than those in the control group(P<0.05). After treatment, the levels of IL-1β, IL-2, IL-6, IL-10, TNF-α and CRP in the experimental group were significantly lower than those in the control group(P<0.05). Conclusions High throughput hemodialysis and hemoperfusion can effectively remove β2-MG in patients with nephritis, inhibit the body's inflammatory response, improve renal function, effective, worthy of promotion. Key words: Nephritis; Renal Dialysis; Hemoperfusion; beta 2-Microglobulin

Associations between small and middle molecules clearance and the change of cognitive function in peritoneal dialysis

BackgroundUremic toxins have been suspected as potential contributors for cognitive impairment in peritoneal dialysis (PD) patients. However, associations between the clearance of serum small and middle molecules and the change of cognitive function were not fully explored and then we explored this issue in the present study.MethodA total of clinically-stable 222 patients on PD were enrolled and then followed up for 2 years in this single-center prospective cohort study. Small and middle molecules clearances were examined by urea clearance (Kt/V), creatinine clearance (Ccr) and beta-2 microglobulin (B2M) clearance via dialysate and urine at baseline and after 2 years. Global and specific cognitive impairment were measured at baseline and after 2 years. Modified Mini-Mental State Examination (3MS) was assessed for global cognitive function, trail-making tests A and B for executive function and subtests of the battery for the assessment of neuropsychological status for immediate and delayed memory, visuospatial skills and language ability.ResultsThe median of total Kt/V, Ccr and B2M clearance were 1.89, 53.2 l/w/1.73 m2 and 17.5 l/w/1.73 m2, respectively at baseline. The prevalence of global cognitive impairment was 12.3% for 222 patients and 15.4% for the remained 130 patients after 2 years. At baseline, total Kt/V was independently positively associated with delayed memory function. Total and dialysate beta-2 microglobulin clearance was positively associated with 3MS scores and negatively with completion time on trail A after multivariate adjustment. At 2 years, we observed a significant difference in the changing trend of 3MS scores between groups divided by total B2M clearance (P = 0.033), which still maintained to be meaningful after multivariate adjustment (P = 0.024). Patients with total B2M clearance > 19.0 l/w/1.73 m2 got significant improvement on their 3MS scores (P = 0.005). Patients divided by total Kt/V or Ccr were not significantly different in the trends of general and any specific cognitive function during the follow up.ConclusionThe higher middle molecules clearance independently correlated to better performance on general cognitive and executive function in PD patients, which also predict an improvement in general cognitive function during the follow up.

The effects of intradialytic exercise on hemodialysis adequacy: A systematic review.

Dialysis adequacy is an independent predictor of high mortality rates in hemodialysis patients. Intradialytic exercise is a potential strategy to increase uremic solute removal by increasing blood flow to low perfusion tissue beds. The purpose of this review is to establish the efficacy of intradialytic exercise for hemodialysis adequacy. Additionally, this review aims to provide practical information to aid health care professionals implement intradialytic exercise for dialysis adequacy. Database and hand searches identified 15 published interventional studies that implemented intradialytic exercise for dialysis adequacy as a primary outcome measure in adult maintenance hemodialysis patients. Data pertaining to dialytic solute clearance of urea, creatinine, beta2 microglobulin, phosphate, and potassium were extracted. Mean differences, normalized to percentages, and effect sizes were calculated and reported. The current data pertaining to the use of intradialytic exercise for improving dialysis adequacy in terms of Kt/Vurea or small molecule uremic toxin clearance are equivocal. Limited data showed that intradialytic exercise has no effect middle molecule toxin (beta2 - microglobulin) clearance. Intradialytic exercise favored increased phosphate removal showing medium to large effects for reduced serum concentrations, reduced rebound and increased clearance. In summary, supervised light to moderate intradialytic aerobic cycling appears to be beneficial for increasing phosphate removal and may be an adjunct therapy for patients failing to meet clinical phosphate targets. Further work is required to establish the effect of intradialytic exercise on Kt/Vurea and other middle molecule and protein bound solutes. Research aimed at establishing the most effective exercise prescription for improved solute clearance is warranted.

Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.

Background Recent meta-analyses suggest that higher removal of beta-2 microglobulin (β2M) with either high-flux (HFD) dialysis or hemodiafiltration (HDF) may be associated with decreased total and cardiovascular mortality in dialysis patients. However, there are limited data about the performance of high flux dialyzers and/or convective therapies in removing β2M. Methods This is a random effects meta-analysis and meta-regression of data extracted from randomized controlled trials and observational studies in hemodialysis, hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove β2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE. Results We included 69 studies from 1 January 2001 to 12 June 2017 on 1879 patients with 6771 available measurements. Average β2M clearance was 48.75 mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis, and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration and HDF) with substantial heterogeneity among studies [P (Q) ≤ 0.001]. In multivariable meta-regression analyses, we found significantly higher β2M clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone membranes in convective therapies. However, the mass of β2M removed into the dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279, 95% CI -9.8 to -34.757, P < 0.001) β2M clearances were significantly lower than whole blood clearances, suggesting that adsorption contributes substantially to β2M removal. Higher Kuf, blood flow and substitution fluid rates but not dialysate flow rates were associated with statistically significant and clinically meaningful elevation in β2M clearance from the body independent of the dialysis modality. Conclusions Membrane composition and characteristics, modality (convective versus diffusive), blood flow rates and substitution fluid rates in HDF play a significant role in the efficient removal of β2M from the body in both diffusive and convective dialysis.

Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.

Recent meta-analyses suggest that higher removal of beta-2 microglobulin (β2M) with either high-flux (HFD) dialysis or hemodiafiltration (HDF) may be associated with decreased total and cardiovascular mortality in dialysis patients. However, there are limited data about the performance of high flux dialyzers and/or convective therapies in removing β2M. This is a random effects meta-analysis and meta-regression of data extracted from randomized controlled trials and observational studies in hemodialysis, hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove β2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE. We included 69 studies from 1 January 2001 to 12 June 2017 on 1879 patients with 6771 available measurements. Average β2M clearance was 48.75 mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis, and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration and HDF) with substantial heterogeneity among studies [P (Q) ≤ 0.001]. In multivariable meta-regression analyses, we found significantly higher β2M clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone membranes in convective therapies. However, the mass of β2M removed into the dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279, 95% CI -9.8 to -34.757, P < 0.001) β2M clearances were significantly lower than whole blood clearances, suggesting that adsorption contributes substantially to β2M removal. Higher Kuf, blood flow and substitution fluid rates but not dialysate flow rates were associated with statistically significant and clinically meaningful elevation in β2M clearance from the body independent of the dialysis modality. Membrane composition and characteristics, modality (convective versus diffusive), blood flow rates and substitution fluid rates in HDF play a significant role in the efficient removal of β2M from the body in both diffusive and convective dialysis.

Clinical outcomes for maintenance hemodialysis patients using a high-flux (FX60) dialyzer

Aims: To investigate the clinical outcomes of maintenance hemodialysis (HD) patients using a high-flux (FX60) dialyzer. Method: Thirty patients undergoing dialysis for at least 2 years with a low-flux dialyzer were switched to the FX60 dialyzer for 3 years. Clinical and biochemical analysis was performed monthly for each patient. The parameters monitored included blood pressure, hemoglobin, albumin, intact parathyroid hormone (iPTH), calcium and phosphorus levels, the adequacy of dialysis (Kt/V), beta2-microglobulin (β2-MG) clearance rate, as well as antihypertensive and erythropoietin (EPO) medications. Results: After 3 years of dialysis with an FX60 dialyzer, the mean arterial blood pressure fell, hemoglobin increased, serum phosphate level decreased, iPTH declined and medication doses decreased. Conclusions: Dialysis with the FX60 dialyzer has a better clinical outcome for rectifying renal anemia, controlling hypertension and lowering serum phosphate levels making it a better choice for long-term HD patients.

Computational assessment of the effects of a pulsatile pump on toxin removal in blood purification

BackgroundFor blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods.MethodsWe devised a new mathematical lumped model to assess the toxin removal efficiency of blood purification systems in patients, integrating the mass transfer model for a human body with a dialyser. The human body model consists of a three-compartment model of body fluid dynamics and a two-compartment model of body solute kinetics. We simulated three types of blood purification therapy with the model, hemofiltration, hemodiafiltration, and high-flux dialysis, and compared the simulation results in terms of toxin (urea and beta-2 microglobulin) clearance and the treatment dose delivered under conditions of pulsatile and non-pulsatile pumping. In vivo experiments were also performed to verify the model results.ResultsSimulation results revealed that pulsatile flow improved the convective clearance of the dialyser and delivered treatment dose for all three types of therapy. Compared with the non-pulsatile pumping method, the increases in the clearance of urea and beta-2 microglobulin with pulsatile pumping were highest with hemofiltration treatment (122.7% and 122.7%, respectively), followed by hemodiafiltration (3.6% and 8.3%, respectively), and high-flux dialysis (1.9% and 4.7%, respectively). EKRc and std Kt/V averaged 28% and 23% higher, respectively, in the pulsatile group than in the non-pulsatile group with hemofiltration treatment.ConclusionsThe pulsatile effect was highly advantageous for all of the toxins in the hemofiltration treatment and for β2-microglobulin in the hemodiafiltration and high-flux dialysis treatments.

Enhanced solute removal with intermittent, in‐center, 8‐hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end-stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and beta-2-microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice-weekly, in-center, 8-hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45+/-7 years). Serum creatinine levels decreased from 9.2+/-1.9 to 3.0+/-1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7+/-1.9 to 2.5+/-0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8+/-5.5 mg/L predialysis to 14.9+/-7.0 mg/L at 8 hours (P<0.01). Dialysate-side clearances of phosphorus and creatinine were 136+/-13 and 143+/-27 cm(3)/min, respectively. Phosphorus clearances were steadily maintained during the 8-hour session. A total of 904+/-292 mg of phosphorus was removed during the 8-hour treatment, with 501+/-174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one-half of the session. The overall calculated B2M clearance was 55.1+/-40.3 cm(3)/min using the immediate post-B2M value and 28.4+/-34.2 mg/L using the 30-minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8-hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.

Frequent Hemodialysis Network (FHN) randomized trials: Study design

Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5-2.75 h, 6 days/week, with target eK(t)/V(n) > or = 0.9/session, whereas nocturnal HD will be delivered for > or = 6 h, 6 nights/week, with target stdK(t)/V of > or = 4.0/week. Subjects will be followed for 1 year. The composite of mortality with the 12-month change in (i) left ventricular mass index (LVMI) by magnetic resonance imaging, and (ii) SF-36 RAND Physical Health Composite (PHC) are specified as co-primary outcomes. The seven main secondary outcomes are between group comparisons of: change in LVMI, change in PHC, change in Beck Depression Inventory score, change in Trail Making Test B score, change in pre-HD serum albumin, change in pre-HD serum phosphorus, and rates of non-access hospitalization or death. Changes in blood pressure and erythropoiesis will also be assessed. Safety outcomes will focus on vascular access complications and burden of treatment. Data will be obtained on the cost of delivering frequent HD compared to conventional HD. Efforts will be made to reduce bias, including blinding assessment of subjective outcomes. Because no large-scale randomized trials of frequent HD have been previously conducted, the first year has been designated a Vanguard Phase, during which feasibility of randomization, ability to deliver the interventions, and adherence will be evaluated.

Adequacy of automated peritoneal dialysis with and without manual daytime exchange: A randomized controlled trial

Until now, it remains unclear whether the addition of manual daytime exchanges or increasing the nightly dialysate flow is the best strategy to optimize automated peritoneal dialysis (APD) treatment. In this open-label randomized controlled crossover trial, 18 patients with high-average (HA) or low-average (LA) peritoneal transport rates sequentially underwent two different APD regimens for 7 days each, with an intermittent washout period of 7 days. 'Manual exchange' treatment was a conventional APD with low nightly dialysate flow and one manual daytime exchange. 'High-flow' treatment was defined by cycler therapy with high dialysate flow but without manual daytime exchange. Creatinine clearances (8.56+/-1.22 vs 7.87+/-1.04 l/treatment, P = 0.011) and urea nitrogen clearances (12.83+/-1.98 vs 11.68+/-1.06 l/treatment, P = 0.014) were significantly increased during 'high-flow' treatment compared to 'manual exchange' treatment. Sodium removal was significantly lower and glucose absorption was higher with the 'high-flow' regimen. Phosphate clearances, beta2-microglobulin clearances, ultrafiltration, and peritoneal protein loss were not different between the two treatment modalities. Subgroup analysis dependent on peritoneal transport types showed that the effect on clearances was most marked and significant in HA transporters, whereas sodium removal was lowest in LA transporters. We conclude that small solute clearances can be significantly improved and middle molecule clearances maintained in APD patients by increasing the nightly dialysate flow instead of adding a manual daytime exchange. However, the possible benefit of better clearances with higher nightly treatment volumes has to be weighed against increased costs and the possible negative impact of impaired sodium removal, especially in LA transporters.

ASAIO 52nd annual conference, Chicago, Illinois, June 8–10, 2006

ASAIO 52nd annual conference, Chicago, Illinois, June 8–10, 2006

Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss

The aim of the present study was transmembrane pressure (TMP) modulation in high-volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a feedback control of TMP were defined in this prospective randomized study in order to obtain maximal efficiency in solute removal while minimizing potential side effects. Two different TMP profiles in mixed HDF were compared in 12 unselected patients who underwent two study periods of 2 weeks each in cross-over randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in which TMP was slowly increased from a low initial value to the maximal value. In both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28 ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/-19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration coefficients and lower resistance indexes. This study showed that the TMP feedback modulation in mixed HDF was highly effective in maintaining very high ultrafiltration rates and filtration fractions, and minimized potential side effects as a result of the improved preservation of membrane permeability and more favorable dialyzer pressure regimen.

The amylase-to-creatinine clearance ratio--a non-specific response to acute illness?

It was felt that the apparent specificity of the amylase-to-creatine clearance ratio (ACCR) in several previous studies of pancreatitis might reflect a failure to utilize adequately ill control subjects. The ACCR and the renal clearances of beta 2-microglobulin (B2-m), similarly related to creatinine (BCCR) as well as the urinary concentration of albumin, were compared in 27 patients with acute pancreatitis, 8 with a perforated peptic ulcer and 7 with mild biliary colic, during the first 5 days in hospital. Acute pancreatitis was graded as mild (6), moderate (14) or severe (7), using a combination of clinical data, diagnostic peritoneal lavage and multiple criteria. Further assessment of the severity of the acute illness was obtained from measurement of C-reactive protein (C-RP). Lowest C-RP levels were found in the patients with mild pancreatitis and biliary colic, and highest levels in the patients with severe pancreatitis and perforated ulcer (P less than 0.002). Similarly, ACCR and BCCR levels were significantly lower in the two mild groups than in the two severe ones (P less than 0.01 and less than 0.002 respectively), although plasma amylase was raised only in patients with pancreatitis and plasma B2-m was similar in all groups. Electrophoresis of urine showed dense bands of tubuloprotein in patients from both severe groups. Urine albumin was higher in severe pancreatitis than in perforated ulcer (P less than 0.1), perhaps indicating a more specific glomerular lesion in pancreatitis. Thus a rise in amylase clearance appeared to be related to the severity of the acute illness, and may be a component of a non-specific tubuloproteinuria. In this study patients with a perforated peptic ulcer had increases in ACCR similar to those seen in patients with severe pancreatitis, and we are therefore doubtful whether ACCR has any role in the clinical diagnosis of pancreatic disease.

The Effect of High-Flux Hemodialysis on Dialysis-Associated Amyloidosis

Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (β2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of β2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p < 0.001). During the follow-up period, while β2-MG levels decreased significantly in the high-flux group (p < 0.05), there was an increase in the low-flux group (p < 0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of β2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins.

Mid-dilution on-line haemodiafiltration in a standard dialyser configuration

Mid-dilution haemodiafiltration (HDF) results in an improved middle molecule removal compared with standard HDF. The OLpur MD 190 haemodiafilter represents a new dialyser design exclusively for mid-dilution on-line HDF. Compared with standard haemodialysers, structural changes in the headers allow the infusion of high replacement fluid volumes after a first post-dilution and before a second pre-dilution stage. We compared in vitro the new device [blood flow (QB) 400 ml/min, substitution flow (QS) 100 and 200 ml/min, dialysate flow (QD) 800 ml/min] with a conventional high-flux dialyser of the same surface area in haemodialysis (HD) (QD 500 ml/min) and post-dilution HDF (at QS 60, QD = 500 ml/min and at QS 100, QD = 800 ml/min) modes. Subsequently, we performed an initial clinical application of the new device in six mid-dilution HDF treatments of five end-stage renal disease patients (QB 400 ml/min, QS 200 ml/min, QD 800 ml/min, treatment duration 205+/-23 min). In vitro urea and beta2-microglobulin clearances in mid-dilution HDF were, respectively, 309.2+/-5.5 and 144.4+/-15.2 ml/min (QS 100) and 321.6+/-4.1 and 204.9+/-4.1 ml/min (QS 200), compared with 278.6+/- 17.2 and 94.0+/-7.6 ml/min in HD, and 310.8+/-10.2 and 123.0+/-6.5 ml/min (QS 60) and 323.6+/-11.2 and 158.0+/-10.3 ml/min (QS 100) in post-dilution HDF. The in vivo trials showed the clinical utility of the device and confirmed the in vitro data: urea and beta2-microglobulin clearances were, respectively, 324.6+/- 10.9 and 207.9+/-29.3 ml/min, while reduction ratios were 75.0+/-5.5 and 83.6+/-4.7%. Our preliminary results need confirmation in a prospective cross-over study. However, the Nephros MD 190 haemodiafilter promises to be a true technological step ahead in terms of improved beta2-microglobulin removal.

Dose of dialysis: Key lessons from major observational studies and clinical trials

Dose of dialysis: Key lessons from major observational studies and clinical trials

Removal of middle molecules and protein-bound solutes by peritoneal dialysis and relation with uremic symptoms

Current guidelines for peritoneal dialysis adequacy are based on kinetics of small water-soluble molecules and do not consider the role of other compounds such as middle molecules and protein-bound solutes. Information on the elimination characteristics of the latter solutes by peritoneal dialysis is limited. Moreover, their relation with uremic symptoms remains unclear. The aim of the present study was (1) to investigate the relative contribution of residual renal function to the overall clearances of beta2-microglobulin (beta2m), a middle molecule, and p-cresol, a protein-bound solute, in adults on peritoneal dialysis as compared to small water-soluble molecules and (2) to evaluate relations between serum levels and uremic symptoms. We performed a cross-sectional observational study, including 30 nonanuric peritoneal dialysis patients. Total, peritoneal, and renal clearances were calculated for urea nitrogen (60 D), creatinine (113 D), phosphate (96 D), beta2m (11.8 kD), and p-cresol (108 D). All patients were asked to complete a uremic symptom questionnaire. Declining total clearances (L/week/1.73 m2) were measured for urea nitrogen, creatinine, phosphate, beta2m, and p-cresol, respectively: 97.3 +/- 4.6, 98.9 +/- 6.1, 64.0 +/- 3.4, 23.1 +/- 2.6, and 17.5 +/- 2.3 (Friedman test P < 0.001). Conversely, the contribution of residual renal function (%) to the respective solute clearances increased significantly: 31.6 +/- 3.2, 51.0 +/- 4.0, 42.4 +/- 4.0, 68.0 +/- 5.4, 61.9 +/- 4.6 (Friedman test P < 0.001). The serum level of p-cresol, but of none of the other solutes examined, correlated significantly with the symptom score (Pearson r= 0.48, P= 0.008). During peritoneal dialysis p-cresol behaves like beta2m, probably due to its protein binding. The total clearance of both molecules is significantly lower as compared to water-soluble solutes and mainly depends on residual renal function. Our data further suggest that protein-bound solutes are involved in the pathophysiology of uremic symptoms.

Beta-2 microglobulin in ESRD: an in-depth review

Beta-2 microglobulin is the most widely studied low-molecular-weight protein in end-stage renal disease. It is known to cause dialysis-related amyloidosis (DRA), by virtue of its retention when renal function fails, its deposition in tissues, its aggregation into fibrils, and its ability to become glycosylated. The onset of DRA may be protracted by the use of noncellulosic membranes, especially when high-volume hemodiafiltration is used in the treatment of renal failure. Adsorptive methods have been developed to improve the removal of beta-2 microglobulin. There seems to be a relative risk reduction in mortality when patients are treated with dialysis membranes that have a higher clearance of beta-2 microglobulin.

Determination of extra renal clearance and generation rate of beta2-microglobulin in hemodialysis patients using a kinetic model.

Beta-2-microglobulin (beta2-m) has been proposed as a marker of middle molecules to assess one aspect of the efficacy of dialysis. Until now, few data have been published about extra renal (metabolic) clearance and generation rates of beta2-microglobulin, which are necessary for calculation of total clearance and mass removal of beta2-m in hemodialysis patients. We have developed a simple method to derive extra renal clearance and generation rates of beta2-m by measuring the pre and post dialysis blood concentrations of beta2-m using kinetic modeling. Ten stable hemodialysis patients were included in this study. Pre and post dialysis concentrations of beta2-m were measured during dialysis with low flux dialyzers (F6 HPS) and after 10 days switching to high flux dialyzers (F60S or Superflux). With a validated two pool model, the generation rate of beta2-m can be determined if extra renal clearance is known. Assuming the generation rate of beta2-m to be constant in each patient, the computer reiterated the calculation of extra renal clearance until the calculated generation rate was equal for both the low flux and the high flux dialyzer. Extra renal clearance was found to be between 1.97 and 4.11 ml/min (average, 3.2 ml/min). Generation rate was found in a rather narrow range between 1.63 and 2.56 mg/kg per day (average, 2.09 mg/kg per day). There was no correlation between extra renal clearance and generation rates. With this simple method, extra renal clearance and generation rates of beta2-m can be determined using data by switching hemodialysis patients from impermeable to permeable membranes.

Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD.

Prostaglandins can affect the vascular response and are locally produced in the peritoneal cavity. Prostaglandin inhibition in continuous ambulatory peritoneal dialysis (CAPD) patients during peritonitis using indomethacin intraperitoneally was found to decrease the intrinsic permeability to macromolecules. In the present study the effects of prostaglandin inhibition were studied during stable, uninfected CAPD. Two standard peritoneal permeability analyses (1.36% glucose) were performed in 10 stable CAPD patients within 1 week with and without addition of 12.5 mg/l indomethacin. Furthermore, possible effects on the parameters of nitric oxide synthesis were determined. In five other patients a high dose of indomethacin was tested. The night before the indomethacin test, 12.5 mg/l indomethacin was added to the nightdwell and the test was performed with 25 mg/l indomethacin. In the normal dose indomethacin group, the dialysate concentrations of prostaglandin (PG) 6-keto-PGF1alpha and thromboxane (Tx) TxB2 were significantly lower with indomethacin (IND) compared with the control dwell (C): 6-keto-PGF1alpha median 93 (C) vs 7.5 (IND) ng/l, P=0.006 and TxB2 12.3 (C) vs 9.0 (IND) ng/l, P=0.04. The dialysate concentration of PGE2 was not different during the control dwell (68.5 ng/l) compared with the indomethacin experiment (50.3 ng/l, P=0.5). The mass transfer area coefficients (MTAC) of nitrate and cGMP, and parameters of nitric oxide synthesis, were similar during both experiments. The MTAC of creatinine and urate were not different with indomethacin: creatinine median 9.5 (C) vs 10.2 ml/min (IND), P=0.2 and urate 7.2 (C) vs 7.3 ml/min (IND), P=0.3. Only the MTAC of urea was marginally higher with indomethacin: 16.0 (C) vs 16.6 ml/min (IND), P=0.04. No differences were found in the clearances of the macromolecules beta2-microglobulin, albumin, IgG and alpha2-microglobulin. With the high indomethacin dose no inhibition of PGE2 was found: 69 (C) vs 63 ng/l(IND), not significant. Furthermore, no differences were found in the transport rates of small solutes or proteins. This indicates no effect of indomethacin on the peritoneal surface area and the size-selective permeability to macromolecules. In both groups no effect was found on the transcapillary ultrafiltration and the effective lymphatic absorption rate during the 4-h dwell. Consequently, the net ultrafiltration, the difference between these, did not change. The indomethacin induced inhibition of the synthesis of 6-keto-PGF1alpha and TxB2 did not lead to alterations in functional parameters of the peritoneal surface area, the intrinsic permeability to macromolecules and fluid kinetics. Therefore, these prostaglandins are not likely to be involved in the regulation of peritoneal transport during stable CAPD.