Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.
One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and beta2-microglobulin (beta2M). The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB = 350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and beta2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (beta2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and beta2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes. (+info)
Fluorimetric determination of aluminum traces in hemodialysis solutions using Mordant Red 19.
A sensitive and accurate method for the spectrofluorimetric determination of trace levels of aluminum in hemodialysis solutions using Mordant Red 19 as the complexation reagent has been developed. The optimal experimental conditions for the concentration of fluorimetric reagent, pH, temperature, and the specific type of matrix are reported. The emission of the fluorescent metal chelate was measured at 555 nm, excitation at 478 nm. Linearity between emission intensity and aluminum concentration was found in the 2-20 ppb range in standard aluminum solutions. Limit of detection was 0.4 ppb. The aluminum amounts in some commercial hemodialysis solutions were determined by means of the extrapolation method. The proposed method proved to be suitable in terms of sensitivity and accuracy for the determination of aluminum in dialysis fluids. (+info)
Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis.
Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. Significant changes in extracorporeal membranes have occurred over the past five decades in which hemodialysis (HD) has been available as a therapy for both acute renal failure (ARF) and end-stage renal disease (ESRD). For cellulosic membranes, these changes have included a reduction in thickness, hydroxyl group substitution, and an increase in pore size. These modifications have resulted in enhanced efficiency of small solute removal, a broader spectrum of overall solute removal, and an attenuation of complement activation in comparison to the thick, unsubstituted cellulosic membranes of low permeability used in the early days of HD therapy. Synthetic membranes, originally developed specifically for use in high-flux HD and hemofiltration, have also evolved during this same time period. In fact, the initially clear distinction between low-flux regenerated cellulosic and high-flux synthetic membranes has become blurred, as membrane formulators have developed products designed to appeal to enthusiasts for both membrane formats. The purpose of this review is to characterize both the solute removal and biocompatibility characteristics of dialysis membranes according to their composition (that is, polymeric makeup) and structure. In this regard, the manner in which membrane biocompatibility interacts with flux is highlighted. (+info)
Standardized thigh muscle area measured by computed axial tomography as an alternate muscle mass index for nutritional assessment of hemodialysis patients.
BACKGROUND: Quantification of muscle mass, which represents the largest protein pool in the body, is important for nutritional assessment but is difficult to achieve with conventional methods in hemodialysis patients. OBJECTIVE: We measured the cross-sectional area of the thigh occupied by muscle by using computed tomography and compared this with other muscle mass indicators. DESIGN: Thigh muscle area (TMA) was examined and correlated with creatinine production and various nutritional indexes in 163 patients undergoing hemodialysis. Where appropriate, TMA was expressed relative to bone area in the thigh (TBA) to avoid the influence of body size. RESULTS: TMA was highly correlated with creatinine production as measured in the spent dialysate (r = 0.85, P < 0.001), indicating that TMA substantially reflects total-body muscle mass. TMA standardized for TBA was negatively correlated with age and positively correlated with other nutritional indicators including body weight, body mass index, serum albumin, serum transthyretin, and protein catabolic rate. Multiple regression analysis revealed that of these variables, age, serum albumin, and protein catabolic rate independently predicted TMA standardized for TBA. By using correlations with various nutritional indicators, we concluded that patients with a value <10.0 for TMA standardized for TBA were likely to be malnourished whereas those with a value >13.0 were likely to be well nourished. CONCLUSIONS: These results indicate that TMA standardized for TBA, measured by computed tomography, is a reliable indicator of muscle mass that could be used for nutritional assessment of hemodialysis patients. (+info)
On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations.
BACKGROUND: The accumulation of beta2-microglobulin (beta2-M) in long-term dialysis patients may lead to dialysis amyloidosis. In this respect, the removal with different modes of on-line haemodiafiltration (HDF) of beta2-M was studied. Long-term clinical observations in patients with more than 10 years of dialysis, treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported. METHODS: In the first part of this report, the reduction ratios and clearances of beta2-M, blood urea nitrogen, creatinine and phosphorus (P) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis (HD). In the second part, we investigated 16 patients with more than 10 years of dialysis treatment. The prevalence of dialysis amyloidosis and the mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol and parathyroid hormone are reported, as well as the mean dose of erythropoietin. RESULTS: In the first part with on-line HDF, starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted. In HDF100 (i.e. with 241 replacement volume per 4-h treatment) vs HD, a beta2-M reduction ratio of 72.7% vs 49.7% (P= 0.0000) and a beta2-M clearance of 116.8 vs 63.8 ml/min (P=0.0000) was obtained. Comparing HDF120 with HDF100, there is a significantly higher beta2-M clearance with the former (P<0.005), although the beta2-M reduction ratio was not significantly better. In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session. If one adds the known 17% adsorption on the polysulfone membrane, a total of 341.6 mg beta2-M per session is removed, which adds up to 1024.8 mg a week. Concerning the small molecules, our results with HDF100 also show a higher creatinine and especially P clearance vs HD. In the second part with 16 patients with more than 10 years of dialysis treatment (mean 14 years 1 month), the mean time on HDF amounted to 39.5% of the total treatment time. In four patients only biocompatible and highly permeable membranes were used, AN69 and mainly polysulfone, and in four other patients these membranes were used for more than 95% of the treatment time. Therefore, it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5% in the patients after 10 years of dialysis. Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis, proposed by van Ypersele de Strihou et al., but without a retrospective X-ray analysis. The mean predialysis beta2-M value was 29.6 mg/l. The mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol were within normal limits. For the parathyroid hormone a mean of 287.5 pg/ml was found. Subtotal parathyroidectomy was performed in five patients. The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature. Conclusions. Like Canaud, in our renal unit, treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient, well-tolerated and safe technique. Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance. However, continuous attention must be paid to an on-line sterile and apyrogenic dialysate. Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment, it also carries a higher cost, which is currently evaluated to be nearly US$11 per session. (+info)
Can sterile and pyrogen-free on-line substitution fluid be routinely delivered? A multicentric study on the microbiological safety of on-line haemodiafiltration.
BACKGROUND: Microbial contamination is characterized not only by the presence of bacteria, but also by high concentrations of biologically active by-products. They are potentially able to cross ultrafiltration and dialysis membranes and stimulate immunocompetent blood cells to synthesize cytokines. In turn, cytokine induction causes acute symptoms and has been incriminated in the long-term complications of haemodialysis patients. Infusion of large volumes of substitution fluids following ultrafiltration of microbially contaminated dialysis fluids may place patients on on-line therapies at particular risk. METHODS: In this study we evaluated 30 machines with a two-stage ultrafiltration system in routine clinical haemodiafiltration settings in six centres for 6 months. Microbiological safety was assessed monthly and at the last use of the filters by determining microbial counts, endotoxin concentration and cytokine-inducing activity. RESULTS: No pyrogenic episodes were observed during the study period. Double-filtration of standard dialysis fluid (range, <1-895 cfu/ml, 0.0028-4.6822 IU/ml) resulted in sterile substitution fluids with endotoxin concentrations well below the Ph.Eur. standard for haemofiltration solutions (range, 0.0014-0.0281 vs 0.25 IU/ml). Moreover, they did not differ from commercial haemofiltration solutions and depyrogenated saline. Likewise, there was no difference in the cytokine-inducing activity between the solutions tested. The high microbiological quality of the ultrafiltered dialysis fluid, which was in the same range as substitution fluid, translates into both the absence of cytokine induction by dialyser back-transport and a redundant safety mode of the on-line system by a second filtration step. CONCLUSION: On-line HDF treatment can routinely be provided with ultra-pure dialysis fluids and sterile substitution fluids at pyrogen-free levels. The online preparation of substitution fluids thus can be considered microbiologically safe. (+info)
Peritoneal kinetics and mesothelial markers in CCPD using icodextrin for daytime dwell for two years.
OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin (Ico), continuous cycling peritoneal dialysis (CCPD) patients were treated for 2 years with either Ico- or glucose (Glu)-containing dialysis fluid for their daytime dwell (14 - 15 hours). Prior to entry into the study, all patients used standard Glu solutions (Dianeal, Baxter BV, Utrecht,The Netherlands). DESIGN: Open, randomized, prospective two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established patients and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years or with peritonitis in the previous month, and women of childbearing potential unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study (19 Glu, 19 Ico). MAIN OUTCOME MEASURES: Daytime dwell peritoneal effluents were collected every 3 months in combination with other study variables (clinical data, laboratory measurements, dialysis-related data, and urine collection). Peritoneal transport studies were carried out every 6 months. RESULTS: In Glu- and Ico-treated patients, peritoneal transport of low molecular weight solutes and protein clearances neither changed during follow-up nor differed between the two groups. Peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen) measured in effluents did not differ between the groups and did not change over time. All these markers showed a dialysate/plasma ratio of more than 1, suggesting local production. Residual renal function remained stable during follow-up and adverse clinical effects were not observed. CONCLUSIONS: Peritoneal membrane transport kinetics and markers remained stable in both groups over a 2-year follow-up period. Membrane markers were higher in effluents than in serum, suggesting local production. No clinical side effects were demonstrated. Icodextrin was a well-tolerated effective treatment. (+info)
Relationship between fill volume, intraperitoneal pressure, body size, and subjective discomfort perception in CAPD patients. Mexican Nephrology Collaborative Study Group.
OBJECTIVE: To determine changes in intraperitoneal pressure (IPP) when dialysate fill volume is increased from 2.0 L to 2.5 L to 3.0 L per exchange, and to evaluate the relationship with subjective discomfort perception. DESIGN: Cross-sectional survey. SETTING: Seven Mexican hospital-based dialysis centers. PATIENTS: Eighty-one adult patients on continuous ambulatory peritoneal dialysis (CAPD) without restriction criteria for age, gender, or time on dialysis, were studied. Patients seropositive for HIV or hepatitis B, and those with cancer or receiving immunosuppressive drugs were excluded. Participants were studied as outpatients. MAIN MEASURES: Blindly and in random order, 2.0-, 2.5-, and 3.0-L volumes of dialysate were infused consecutively. Body surface area (BSA) was calculated from patient height and weight. IPP was assessed with the patient lying supine, measuring the height of the dialysate column inside the peritoneal dialysis bag tubing. Blood pressure and subjective discomfort perception (using a visual analog scale of 0-100 mm) were also evaluated and registered after each of the three exchanges. RESULTS: The IPP rose with each increase of dialysate volume and was higher in males than in females for each fill volume level. For males IPP was 18.9 +/- 6.9, 20.8 +/- 7.1, and 22.9 +/- 7.5 cm H2O; and for females it was 16.5 +/- 5.7, 18.4 +/- 5.5, and 19.7 +/- 6.2 cm H2O for 2.0-, 2.5-, and 3.0-L fill volumes respectively (p < 0.01 among fill volumes and between genders). Intraperitoneal pressure showed significant negative correlation with the fill volume corrected for patient body size as reflected by the dialysate volume/ BSA ratio (r= -0.393, p < 0.01; r= 0.319, p < 0.01; and r= -0.274, p < 0.02 for 2.0-, 2.5-, and 3.0-L fill volumes respectively). Discomfort score rose as fill volume rose, with a median of 0, 2.5, and 13.0 for 2.0-, 2.5-, and 3.0-L fill volumes respectively (p< 0.001). It is interesting, however, that with 2.5-L and 3.0-L dialysate infusion volumes, 64% and 44% of the patients, respectively, had no discomfort at all. CONCLUSION: Dialysate volume increase is associated with higher IPP, which is modulated by the gender and body size of the patients. Although the mean discomfort score was higher with larger dialysate volumes, there was no significant correlation between discomfort and IPP or the dialysate volume/BSA ratio. Many patients had no discomfort with 2.5-L or even with 3.0-L dialysate infusions; theoretically, they can be treated with larger volumes. (+info)