Oxalate removal by daily dialysis in a patient with primary hyperoxaluria type 1.

BACKGROUND: Dialysis patients with primary hyperoxaluria are exposed to risks and hazards associated with calcium oxalate salt deposition in body tissues, since regular dialysis treatment does not adequately correct hyperoxalaemia. The purpose of this study was to evaluate oxalate mass removal using various dialysis modes in a patient suffering from primary hyperoxaluria type 1 (PH1). METHODS: Oxalate kinetics during daily haemodialysis was compared with that of standard haemodialysis (STD HD) and haemodiafiltration (HDF) using high flux dialysers (FB 170 H and FB 210 U, Transdial, Paris, France). All dialysis sessions lasted for 4 h. Blood was withdrawn and spent dialysate was collected in plastic bags every hour to evaluate mass removal. Oxalate concentration in plasma and in spent dialysate was determined by an enzymatic method. Oxalate generation, distribution volume and tissue deposition were calculated using single-pool models adapted from previous studies. RESULTS: Although no significant difference was found in mass removal per session between dialysis strategies and dialyser types, weekly mass removal with daily HD was about 2 times greater than with STD HD or HDF. Even when daily HD was performed, the oxalate generation rate-mass removal ratio (G/R ratio) remained at a value of approximately 2. CONCLUSION: Although daily HD sessions led to a substantial increase in weekly oxalate removal, all three types of renal replacement therapy were insufficient to compensate for estimated oxalate generation. To eliminate sufficient amounts of oxalate generated in PH1 patients, at least 8 h of daily dialysis with a high-flux membrane would probably be required. Renal replacement therapy for PH1 patients needs be improved further.     

Comparison of hemodialysis and hemodiafiltration: a long-term longitudinal study.

Although hemodiafiltration is purported to provide better cardiovascular stability for dialysis patients; other possible benefits of this therapy have not been well defined. We have compared treatment with hemodialysis (HD) and hemodiafiltration (HDF) in 20 stable patients over a period of 18 months. Dialysis parameters (dialysate composition and flow, duration, dialyzer) were the same in the two periods except for the added convection of HDF and a higher tolerated blood flow in HDF. Cardiovascular parameters were remarkably similar in the two treatment periods, indicating that stable patients do not benefit further from this therapy in terms of these factors. The clearance of urea was significantly improved with HDF, which was reflected in a higher Kt/V and lower TACurea. We observed a significant correlation between Kt/V and PRU in both HD and HDF modes. This correlation was linear and the regression line was similar in both modes. The clearance of beta 2-microglobulin was also significantly improved by HDF compared to HD. Thus the benefit of HDF in stable dialysis patients is the improved clearance of small molecules and beta 2-microglobulin without increasing dialysis time. Further clinical benefits due to the improved clearance may only become apparent with longer follow-up.     

Plasma oxalate in patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis or hemodialysis

Plasma oxalate was measured in 20 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and 20 patients receiving hemodialysis (HD). All patients had levels well above the reference range of less than 2.0 to 5.0 mumol/L (less than 0.18 to 0.44 mg/L), the medians being 34 mumol/L (2.99 mg/L) and 42 mumol/L (3.70 mg/L) for the two groups, respectively. Plasma oxalate did not differ significantly in the two groups. Plasma oxalate was not influenced by the number of months patients had received dialysis treatment, but a significant correlation was found between oxalate and creatinine in the 40 patients studied (P less than 0.02, r = 0.38). Predialysis oxalate levels were reduced by approximately 60% following HD, but returned to 80% of the predialysis levels within 24 hours and 95% within 48 hours. Oxalate levels did not differ significantly in samples taken before, during, and after exchanges of CAPD fluid. That the patients treated with CAPD did not have higher oxalate levels than the HD group suggests that the continuous nature of the former treatment compensates for the lower oxalate clearance by the peritoneum. The reported higher risk of oxalosis associated with intermittent peritoneal dialysis has led to a similar risk being postulated for CAPD; however, the present study indicates that if such a risk exists, it cannot be explained by higher levels of oxalate or ionized calcium in these patients.     

Oxalate elimination via hemodialysis or peritoneal dialysis in children with chronic renal failure

. Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7 – 18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12±11 months in CAPD and 31±23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/min per 1.73 m² in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 μmol/1.73 m² surface area/week in CAPD versus 3,915 μmol/1.73 m² per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 μmol/week. Plasma oxalate remained elevated in both procedures [28 – 84 μmol/l in CAPD (92/148 in PH) and 33 – 101 μmol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen. Received May 24, 1995; received in revised form and accepted October 31, 1995     

Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS

Hemodiafiltration (HDF) is used sporadically for renal replacement therapy in Europe but not in the US. Characteristics and outcomes were compared for patients receiving HDF versus hemodialysis (HD) in five European countries in the Dialysis Outcomes and Practice Patterns Study. The study followed 2165 patients from 1998 to 2001, stratified into four groups: low- and high-flux HD, and low- and high-efficiency HDF. Patient characteristics including age, sex, 14 comorbid conditions, and time on dialysis were compared between each group using multivariate logistic regression. Cox proportional hazards regression assessed adjusted differences in mortality risk. Prevalence of HDF ranged from 1.8% in Spain to 20.1% in Italy. Compared to low-flux HD, patients receiving low-efficiency HDF had significantly longer average duration of end-stage renal disease (7.0 versus 4.7 years), more history of cancer (15.4 versus 8.7%), and lower phosphorus (5.3 versus 5.6 mg/dl); patients receiving high-efficiency HDF had significantly more lung disease (15.5 versus 10.2%) and received a higher single-pool Kt/V (1.44 versus 1.35). High-efficiency HDF patients had lower crude mortality rates than low-flux HD patients. After adjustment, high-efficiency HDF patients had a significant 35% lower mortality risk than those receiving low-flux HD (relative risk=0.65, P=0.01). These observational results suggest that HDF may improve patient survival independently of its higher dialysis dose. Owing to possible selection bias, the potential benefits of HDF must be tested by controlled clinical trials before recommendations can be made for clinical practice.     

Clearance and removal of oxalate in children on intensified dialysis for primary hyperoxaluria type 1

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.     

Estimation of residual renal function using beta-trace protein: Impact of dialysis procedures

Beta-trace protein (BTP), a low molecular weight protein of 23-29 kDa, has been proposed as a promising biomarker to estimate residual renal function (RRF) in patients on maintenance hemodialysis (HD). Indeed, BTP is cleared by native kidney but not during conventional HD session. By contrast, the removal rate of BTP using convective processes (mainly hemodiafiltration [HDF]) and peritoneal dialysis (PD) has been little or not investigated. Therefore, an aim of this study was to evaluate the impact of dialysis procedures (high-flux HD, on-line post-dilution HDF and PD) on BTP removal in comparison with beta-2 microglobulin (B2M) and cystatin C (CYSC) removals after a single session. In addition, the ability of BTP to predict RRF in PD was assessed. This observational cross-sectional study included a total of 82 stable chronic kidney disease patients, 53 patients were on maintenance dialysis (with n = 26 in HD and n = 27 in HDF) and 29 were on PD. Serum concentrations of BTP, B2M, and CYSC were measured (a) before and after a single dialysis session in HD and HDF anuric patients to calculate reduction percentages, (b) in serum, 24-hour-dialysate and 24-hour-urine in PD patients to compute total, peritoneal, and urinary clearance. RRF was estimated using four equations developed for dialysis patients without urine collection and compared to the mean of the urea and creatinine clearances in PD. The concentrations of the three studied molecules were significantly reduced (P < .001) after dialysis session with significantly higher reduction ratio using HDF compared to HD modality (P < .001): BTP 49.3% vs 17.5%; B2M 82.3% vs 69.7%; CYSC 77.4% vs 66% in HDF and HD, respectively. In non-anuric PD patients, B2M and CYSC were partly removed by peritoneal clearance (72.3% and 57.6% for B2M and CYSC, respectively). By contrast, BTP removal by the peritoneum was negligible and a low bias for the BTP-based equation to estimate RRF (−1.4 mL/min/1.73 m²) was calculated. BTP is significantly removed by high-flux HD or HDF, thereby compromising its use to estimate RRF. By contrast, BTP appears as a promising biomarker to estimate RRF in PD patients since it is not affected by peritoneal clearance, unlike B2M and CYSC, and it is well correlated to RRF.     

Hemodiafiltration--a new treatment option for hyperphosphatemia in hemodialysis patients.

BACKGROUND: Hemodiafiltration is used to increase the convective transport and thereby the elimination of small and middle molecules, mainly beta2-microglobulin (beta2-M) across the dialysis membranes. There is little information concerning urea, creatinine, beta2-M and principally phosphate kinetics during hemodiafiltration in vivo. In this prospective study, we evaluated the transmembrane solute mass removal (TSR) and clearance (Kd) of urea, creatinine and phosphate as well as serum beta2-M reduction rate (beta2-MRR) and collected beta2-M in dialysate plus ultrafiltrate during high-flux hemodialysis (HD) and post-dilutional hemodiafiltration (HDF). PATIENTS AND METHODS: 16 patients were studied using a polysulfone capillary filter (1.6 m2 surface area, 40 microm fiber internal diameter and 200 microm, wall thickness) during 2 one-week periods: first week HD 1.6 m2 and second week HDF 1.6 m2. Treatment time was 4 hours, blood flow rate 300 ml/min with constant dialysate and ultrafiltration rates for HD and HDF periods. TSR, Kd, beta2-MRR and beta2-M collection were assessed during the mid-week treatment. In a second part of the study, we repeated the same protocol using a second high-flux polysulfone capillary filter (2.4 m2 surface area, 30 microm fiber diameter and 150 microm wall thickness). RESULTS: TSR and Kd of urea and creatinine were not improved by HDF, however, HDF increased TSR and Kd of phosphate. Phosphate clearance rose from 120 (HD 1.6 m2) to 159 (HDF 1.6 m2) (p < 0.005) and from 146 (HD 2.4 m2) to 206 (HDF 2.4 m2) (p < 0.005) ml/min. Beta2-MRR increased from 64.1 +/- 8.6 to 77.7 +/- 8.2% (p < 0.005) and from 75.0 +/- 5.1 to 82.9 +/- 8.5% (p < 0.005) during HDF 1.6 m2 and HDF 2.4 m2, respectively. Collected beta2-M remained unchanged. This discrepancy seems to be due to an enhanced beta2-M adsorption to the polysulfone membrane during HDF. CONCLUSION: Our results provide a strong evidence that HDF has no advantage over HD with respect to urea and creatinine removal in vivo. However, HDF did improve the elimination of phosphate and should be considered as an additional treatment option for hyperphosphatemia in dialysis patients. HDF improves significantly the elimination of beta2-M.     

Oxalate clearance by haemodialysis--a comparison of seven dialysers.

BACKGROUND: In patients with primary hyperoxaluria (PH) and oliguric end-stage renal disease, oxalate removal is largely dependent on the clearance by dialysis. Data on the oxalate clearance of newer dialyser types are scarce or absent. Therefore, we measured oxalate clearances of seven dialysers in a single 52-year-old female patient with PH. Since haemodiafiltration (HDF) has been advocated to increase oxalate clearance, we also assessed the effect of different pre-dilution flows. The goal of the study was to select the dialyser and pre-dilution flow combination with the highest oxalate clearance. METHODS: Oxalate clearances were assessed by simultaneously taking afferent blood and efferent dialysate samples at 30, 60, 120 and 180 min after the start of haemodialysis. Blood flow and dialysate flow were 350 and 500 ml/min, respectively. All dialysers were tested at a pre-dilution flow of 2 l/h. Six dialysers were also tested at either a pre-dilution flow of 4.5 l/h or without HDF, depending on the ultrafiltration coefficient of the dialyser. RESULTS: Oxalate clearances differed markedly between the tested dialysers, ranging from 144+/-10 to 220+/-12 ml/min. The highest oxalate clearances were achieved with HdF100S (219+/-10 ml/min) and Sureflux FB-210U (220+/-12 ml/min) at a pre-dilution flow of 2 l/h. Higher pre-dilution flows (2 l/h vs no HDF or 4.5 vs 2.0 l/h) yielded similar oxalate clearances. CONCLUSION: The highest oxalate clearances were achieved with a high-flux polysulfone and a cellulose triacetate dialyser with a large surface area. Higher pre-dilution flows did not augment oxalate clearance.     

Plasma oxalate levels rise in hemodialysis patients despite increased oxalate removal

The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role.     

Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration

BACKGROUND: Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiologic. On-line hemodiafiltration (OL-HDF) is a HDF technique that combines diffusion with high convection in which the dialysis fluid itself is used as a reinfusion solution. The aim of this study was to demonstrate the beneficial effect of the more effective dialysis schedule (daily dialysis) with the dialysis modality that offers the highest uremic toxin removal (on-line HDF). METHODS: Eight patients, six males and two females, on standard 4 to 5 hours three times a week OL-HDF (S-OL-HDF) were switched to daily OL-HDF (D-OL-HDF) 2 to 21/2 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Tolerance, uremic toxin removal, urea kinetics, biochemical and anemia profiles, blood pressure, and left ventricular hypertrophy were evaluated. RESULTS: D-OL-HDF was well accepted and tolerated. The disappearance of postdialysis fatigue was rapidly reported by patients. Patients mantained the same [time average concentration (TAC) and weekly single-pool Kt/V (spKt/V)] throughout the study. However, equivalent renal urea clearance (EKR), standard Kt/V and weekly urea reduction ratio (URR) were increased during D-OL-HDF. Weekly urea, creatinine, osteocalcin, beta2-microglobulin, myoglobin, and prolactin reduction ratios were improved with D-OL-HDF. There was a significant decrease in predialysis plasma levels of urea, creatinine, acid uric, beta2-microglobulin and homocysteine over 6 months. Phosphate binders were reduced and antihypertensive drugs were stopped. A 30% regression of left ventricular mass was observed. CONCLUSION: The change from S-OL-HDF to D-OL-HDF was well tolerated. Disappearance of postdialysis fatigue, better dialysis adequacy, a higher removal of middle and large molecules, a reduction of phosphate binders, improvement of status nutritional, and an important reduction of cardiovascular risk factors were observed.     

Comparison of predilution hemodiafiltration and low-flux hemodialysis at temperature-controlled conditions using high calcium-ion concentration in the replacement and dialysis fluid

BACKGROUND: It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the hemodynamics of high-dose predilution hemodiafiltration (HDF) and low-flux hemodialysis (HD), under matched conditions and using high calcium-ion concentration in the replacement/dialysis fluid. METHODS: 13 stable hemodialysis patients were investigated in a randomized crossover, blinded controlled trial. The patients were allocated to one session of predilution HDF (substitution fluid 1.20 1/kg BW) and one session of HD at 4.5 hours. At the start of the dialysis the patient's core temperature was "locked" by an automatic feedback system regulating the dialysate temperature, thereby patient's temperature was kept stable throughout the whole treatment. The Ca ion concentration in the substitution/dialysis fluid was 1.75 mM. Cardiac output was measured hourly by the ultrasound velocity dilution method. RESULTS: Within treatments comparisons revealed that both treatments displayed stable mean blood pressure and equally reduced cardiac output. HDF showed decreased stroke volume and increased total peripheral resistance. The pulse rate decreased significantly only during HD. Arterial temperature was kept constant during both treatments. Ultrafiltration volume, cardiopulmonary recirculation, relative blood volume, Kt/V and total energy transfer were matched for HD and HDF. The overall between treatments comparisons revealed no significant differences. CONCLUSIONS: We have shown that during matched conditions and high calcium concentrations, the hemodynamic profiles of high dose predilution HDF and lowflux HD were similar. Both modalities showed stable mean blood pressure profiles. An acute circulatory benefit of convective solute removal over diffusive, could not be demonstrated.     

Clinical improvement by increased frequency of on-line hemodialfiltration.

BACKGROUND/AIMS: In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD. METHODS: One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD. RESULTS: Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week. CONCLUSION: On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD.     

Matching Efficacy of Online Hemodiafiltration in Simple Hemodialysis Mode

PUREMA H (referred to as PES) is an innovative dialysis membrane for enhanced low‐molecular‐weight (LMW) protein removal. The purpose of the study was to prove whether its efficacy in hemodialysis (HD) matches that of online hemodiafiltration (HDF) with conventional high‐flux membranes. In a prospective, randomized, cross‐over study on eight maintenance dialysis patients, treatment efficacy of HD with PES was compared with online postdilution HDF with the two synthetic high‐flux membranes polysulfone (referred to as PSU) and Polyamix (referred to as POX). Apart from the infusion of replacement fluid, which was set at 20% of the blood flow rate of 300 mL/min, operating conditions in HD and HDF were kept identical. Small solute and LMW protein plasma clearances as well as the reduction ratio (RR) of cystatin C and retinol‐binding protein were not different between the therapies. HDF with POX resulted in a significantly lower myoglobin RR as compared with HD with PES, and HDF with PSU. A 4% higher beta₂‐microglobulin RR was determined in HDF with PSU (73 ± 5%) as compared with PES in HD (69 ± 5%). The albumin loss was below 1 g for all treatments. Despite the fact that simple HD did not fully exploit the characteristics of PES, it achieved essentially similar LMW protein removal and albumin loss as compared with online postdilution HDF with the conventional synthetic high‐flux membranes PSU and POX. Therefore, HD with PES may have beneficial effects on the outcome of maintenance dialysis patients similar to high‐efficiency HDF.     

Glucose in the dialyzate does not reduce the free amino acid loss during routine hemodialysis of non-fasting patients

In order to clarify the effect of dialyzate glucose on free amino acid loss during routine 5 hr hemodialysis (HD), 10 stable non-fasting HD patients were dialyzed twice using dialyzates (Na 141, K 2.5, Ca 3.5, Cl 101, Mg 1.5, Acetate 36 mEql) with (500 mg/dl) or without glucose. Total free amino acid loss in the dialyzate and plasma free amino acids were measured using a liquid chromatograph amino acid analyzer. Total free amino acid losses into the dialyzate with and without glucose were 6598 +/- 482, and 6482 +/- 174 mg respectively. This is not statistically significant. The plasma concentration of free amino acid fell considerably during dialysis, but there was no significant difference between the two types of dialyzates used. We concluded that the addition of glucose to the dialyzate does not reduce the free amino acid loss during routine HD of non-fasting patients. This result does not accord with a previous report that adding glucose to the dialyzate decreases the loss of free and bound amino acid during dialysis.     

Kinin kinetics during different dialysis protocols with AN69 dialyser in ACEI-treated patients

The effect of different dialysis modes on kinin kinetics wasstudied in seven stable haemodialysis patients treated withAN69 dialysers and ACE inhibitors (ACEI). AN69 haemodiafiltrationwith calcium-enriched substitution (HDF), AN69 haemodialysiswith 1.75 (HD 1.75) and 1.50 (HD 1.50)mmol/l dialysate calcium,AN69 haemodialysis with 1.25mmol/l dialysate calcium and substitutionof 2.25 mmol/h calcium (HD +Ca), and cellulose acetate haemodiafiltration(CA HDF) were compared. Dialysis was uneventful in all patients.During dialysis, serum calcium, sodium, pH, albumin, and bradykininwere measured at the start and after 5 min at arterial, venous,and postinfusion side of the extracorporeal circuit. Serum predialysisbradykinin was 107±18fmol/ml (mean±SEM) in patientson HDF, 61±9 fmol/ml in patients on HD 1.50, 49±13fmol/ml in patients on HD 1.75, 35±3 fmol/1 in patientson HD±Ca, and 75±27 fmol/ml in CA HDF. No significantchange of mean bradykinin levels occurred after 5 min at thearterial and venous side of the dialyser or postinfusion. Individualhigh bradykinin levels, up to 2672 fmol/ml, were observed butwithout clinical consequences, suggesting that the thresholdvalue is difficult to determine. No significant correlationswere evidenced between bradykinin levels and any of the biochemicalmeasurements. The present data show an intraindividual variabilityof the bradykinin levels with variation coefficients rangingfrom 0.386 to 2.783. The present study illustrates that haemodialysisand haemodiafiltration with AN69 in ACEI-treated patients, underthe present conditions, does not result in anaphy-lactoid reactionsor in a clinically significant release of bradykinin. The occurrenceof anaphylactoid reactions with high bradykinin levels is probablythe result of several concurrent bioincompatible factors insensitized patients.     

Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2

A high delivered Kt/V(urea) (dKt/V(urea)) is advocated in the U.S. National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines on hemodialysis (HD) adequacy, irrespective of the presence of residual renal function. The contribution of treatment adequacy and residual renal function to patient survival was investigated. The Netherlands Cooperative Study on the Adequacy of Dialysis is a prospective multicenter study that includes incident ESRD patients older than 18 yr. The longitudinal data on residual renal function and dialysis adequacy of patients who were treated with HD 3 mo after the initiation of dialysis (n = 740) were analyzed. The mean renal Kt/V(urea) (rKt/V(urea)) at 3 mo was 0.7/wk (SD 0.6) and the dKt/V(urea) at 3 mo was 2.7/wk (SD 0.8). Both components of urea clearance were associated with a better survival (for each increase of 1/wk in rKt/V(urea), relative risk of death = 0.44 [P < 0.0001]; dKt/V(urea), relative risk of death = 0.76 [P < 0.01]). However, the effect of dKt/V(urea) on mortality was strongly dependent on the presence of rKt/V(urea), low values for dKt/V(urea) of <2.9/wk being associated with a significantly higher mortality in anuric patients only. Furthermore, an excess of ultrafiltration in relation to interdialytic weight gain was associated with an increase in mortality independent of dKt/V(urea). In conclusion, residual renal clearance seems to be an important predictor of survival in HD patients, and the dKt/V(urea) should be tuned appropriately to the presence of renal function. Further studies are required to substantiate the important role of fluid balance in HD adequacy.     

Change from conventional haemodiafiltration to on-line haemodiafiltration.

BACKGROUND: On-line haemodiafiltration (HDF) is a technique which combines diffusion with elevated convection and uses pyrogen-free dialysate as a replacement fluid. The purpose of this study was to evaluate the difference between conventional HDF (1-3 l/h) and on-line HDF (6-12 l/h). METHODS: The study included 37 patients, 25 males and 12 females. The mean age was 56.5 +/- 13 years and duration of dialysis was 62.7 +/- 49 months. Three patients dropped out for transplantation, three patients died and three failed to complete the study period. Initially all patients were on conventional HDF with high-flux membranes over the preceding 34 +/- 32 months. Treatment was performed with blood flow (QB) 402 +/- 41 ml/min, dialysis time (Td) 187 min, dialysate flow (QD) 654 +/- 126 ml/min and replacement fluid (Qi) 4.0 +/- 2 l/session. Patients were changed to on-line HDF with the same filtre and dialysis time, QD 679 +/- 38 ml/min (NS), QB 434 +/- 68 ml/min (P < 0.05) and post-dilutional replacement fluid 22.5 +/- 4.3 l/session (P < 0.001). We compared conventional HDF with on-line HDF over a period of 1 year. Dialysis adequacy was monitored according to standard clinical and biochemical criteria. Kinetic analysis of urea and beta2-micro-globulin (beta2m) was performed monthly. RESULTS: Tolerance was excellent and no pyrogenic reactions were observed. Pre-dialysis sodium increased 2 mEq/l during on-line HDF. Plasma potassium, pre- and post-dialysis bicarbonate, uric acid, phosphate, calcium, iPTH, albumin, total proteins, cholesterol and triglycerides remained stable. The mean plasma beta2m reduction ratio increased from 56.1 +/- 8.7% in conventional HDF to 71.1 +/- 9.1% in on-line HDF (P < 0.001). The pre-dialysis plasma beta2m decreased from 27.4 +/- 8.1 to 24.2 +/- 6.5 mg/l (P < 0.01). Mean Kt/V (Daugirdas 2nd generation) was 1.35 +/- 0.21 in conventional HDF compared with 1.56 +/- 0.29 in on-line HDF (P < 0.01), Kt/Vr (Kt/V taking into consideration post-dialysis urea rebound) 1.12 +/- 0.17 vs 1.26 +/- 0.20 (P < 0.01), BUN time average concentration (TAC) 44.4 +/- 9 vs 40.6 +/- 10 mg/dl (P < 0.05) and protein catabolic rate (PCR) 1.13 +/- 0.22 vs 1.13 +/- 0.24 g/kg (NS). There was a significant increase in haemoglobin (10.66 +/- 1.1 vs 11.4 +/- 1.5) and haematocrit (32.2 +/- 2.9 vs 34.0 +/- 4.4%), P < 0.05, during the on-line HDF period, which allowed a decrease in the erythropoietin doses (3861 +/- 2446 vs 3232 +/- 2492 UI/week), (P < 0.05). Better blood pressure control (MAP 103.8 +/- 15 vs 97.8 +/- 11 mmHg, P < 0.01) and a lower percentage of patients requiring antihypertensive drugs were also observed. CONCLUSION: The change from conventional HDF to on-line HDF results in increased convective removal and fluid replacement (18 l/session). During on-line HDF treatment, dialysis dose was increased for both small and large molecules with a decrease in uraemic toxicity level (TAC). On-line HDF provided a better correction of anaemia with lower dosages of erythropoietin. Finally, blood pressure was easily controlled.     

Solute kinetics in hypertonic hemodiafiltration and standard hemodialysis

Hemodiafiltration (HDF) is a new dialysis treatment that combines convective and diffusive forces. In order to assess the efficiency of a peculiar model of hypertonic HDF (H HDF), we studied eight uremic patients when they were undergoing five sessions of H HDF of 180 minutes duration and two sessions of standard hemodialysis (HD) of 270 minutes duration with a comparable blood (approximately 400 mL/min) and dialysate flow rate (approximately 520 mL/min). The plasma water clearances (Kw) of small [urea (U), creatinine (C), uric acid (UA), and phosphorus (P)] and middle molecules [netilmicin (N) and inulin (I)] were exceedingly higher in H HDF than in HD; however, because of the different treatment times, U and C removal (R) in HD overcame and UA and P R in HD equalized that in H HDF. The factor time was not sufficient to HD to compensate for the large difference in Kw in the case of I. Additional studies were performed in seven out of the eight patients after two sessions of H HDF and one session of HD. Two significantly higher rebounds were observed when comparing both treatments: for U after HD and for parathyroid hormone (PTH) after H HDF; however, PTH Cx/Cs ratios (ratios of the plasma water concentration of PTH at any postdialysis time to the plasma water concentration of PTH at the start of the run) were not different in both treatments, meaning that there was an increased PTH secretion in the early post H HDF hours in order to compensate for the larger PTH R with H HDF.(ABSTRACT TRUNCATED AT 250 WORDS)