Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.

Increases in mass transfer-area coefficients and urea Kt/V with increasing dialysate flow rate are greater for high-flux dialyzers.

The hemodialyzer mass transfer-area coefficient (K(o)A) for urea increases with increasing dialysate flow rate (Q(d)). The magnitude of the increase in K(o)A varies depending on the particular dialyzer under consideration; however, dialyzer properties that govern this phenomenon have not been established. We hypothesized that Q(d)-dependent increases in K(o)As are influenced by the water permeability of the dialysis membrane. We evaluated in vitro the effect of blood flow rate (Q(b)) and Q(d) on urea and creatinine K(o)As for two low-flux (Polyflux 6L and 8L) and two high-flux (Polyflux 14S and 17S) dialyzers containing Polyamide S membranes with similar membrane surface areas. Additional experiments were also performed on high-flux dialyzers containing Polyamide S membranes with very large surface areas (Polyflux 21S and 24S). K(o)As, calculated from the mean of blood- and dialysate-side clearances, were determined at zero net ultrafiltration for three different Q(b) and Q(d) combinations: Q(b) of 300 mL/min and Q(d) of 500 mL/min; Q(b) of 450 mL/min and Q(d) of 500 mL/min; and Q(b) of 450 mL/min and Q(d) of 800 mL/min. Urea and creatinine K(o)As were independent of the Q(b) but increased when Q(d) was increased from 500 to 800 mL/min. These increases in both urea and creatinine K(o)As were greater for high-flux than low-flux dialyzers (P < 0.0001). As expected, urea and creatinine K(o)As also increased with increasing membrane surface area. We conclude that dialysis membrane water permeability (or flux) is a dialyzer property that influences the dependence of small-solute K(o)As and clearance on Q(d). Whether this phenomenon is caused by enhanced internal filtration for dialyzers containing high-flux membranes requires further study.

Noninvasive transcutaneous determination of access blood flow rate.

BACKGROUND: Current indicator dilution techniques for determining the vascular access blood flow rate (Qa) require reversal of the dialysis blood lines and are time consuming. We have recently described an indicator dilution technique for determining Qa using a novel optical transcutaneous hematocrit (Hct) sensor that does not require reversal of the dialysis lines, and have validated the accuracy of this method (TQa) in vitro. METHODS: This study compared results using the TQa method with those obtained using a similar indicator dilution technique but which required reversal of the dialysis lines (HD01 Monitor, Transonic Systems, Ithaca, NY, USA) during routine hemodialysis in 59 patients (25 native fistulas and 34 synthetic grafts). The sensor for the TQa method was placed on the skin directly over the access to measure changes in Hct approximately 25 mm downstream of the venous needle. A single 30 mL bolus of saline was infused into the dialyzer venous line over approximately six seconds without reversal of the dialysis blood lines, and the vascular access flow rate was calculated using indicator dilution methods from the time-dependent decrease in the Hct downstream of the venous needle. Two additional small-scale studies were performed to assess the effect skin pigmentation and to evaluate further the reproducibility of the TQa method. RESULTS: Qa values determined by the TQa method were highly correlated with those determined by the HD01 method (N = 72, R2 = 0.948, P < 0.001) over the range of 153 to 2,042 mL/min. There was no significant difference between vascular access flow rates determined by the TQa method and those determined by the HD01 METHOD: Results from one small-scale study showed that the relationship between Qa values determined by the TQa and the HD01 methods was similar when tested only among black patients (N = 12), suggesting that skin pigmentation is not an important determinant of the accuracy of the TQa METHOD: The second small-scale study showed that the intratreatment coefficient of variation for the TQa method was 7.8 +/- 5.6% (N = 14). CONCLUSIONS: : These results show that transcutaneous measurement of Qa is an accurate, simple, and fast technique for determining Qa without requiring the reversal of the dialysis blood lines.

Effect of indomethacin on peritoneal protein loss in a rabbit model of peritonitis.

BACKGROUND: Although various inflammatory mediators have been previously shown to be released into the peritoneal cavity during peritonitis in peritoneal dialysis patients, those that are involved in governing changes in peritoneal permeability to small solutes and protein remain incompletely defined. METHODS: We determined the importance of prostanoid production in the enhanced protein loss observed during acute peritonitis by inhibition experiments using indomethacin, an inhibitor of cyclooxygenase activity. The association between changes in peritoneal permeability and the generation of inflammatory mediators after adding Escherichia coli to peritoneal dialysate was first examined in series 1 experiments. Series 2 experiments then determined the effect of intraperitoneal administration of indomethacin (75 microg/mL) on changes in peritoneal permeability after adding E. coli to peritoneal dialysate. All experiments were performed in male New Zealand White rabbits (2.6 to 3.4 kg body weight) using an eight-hour dwell of dialysate containing 2.5% glucose. Peritoneal permeability to creatinine and protein was assessed by time-dependent changes in the dialysate to plasma concentration ratios of these solutes. RESULTS: Series 1 experiments showed enhanced leukocyte migration into the peritoneal cavity and increased peritoneal permeability to protein during bacterial challenge that was accompanied by an increase in the dialysate concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and interleukin-8, but not nitrate + nitrite (a measure of local nitric oxide production). Inhibition of prostanoid production by intraperitoneal administration of indomethacin in series 2 experiments resulted in lower dialysate concentrations of PGE2 and 6-keto-PGF1alpha and in lower peritoneal permeability to protein, both to control levels. No effect of indomethacin on transperitoneal migration of leukocytes or the generation of interleukin-8 was observed. CONCLUSIONS: Enhanced production of prostanoids likely plays an important role in governing the increase in peritoneal permeability to protein during acute, bacterial peritonitis in the rabbit.

Potential of dual-skinned, high-flux membranes to reduce backtransport in hemodialysis.

BACKGROUND: Potential backfiltration of cytokine-inducing material is a clinical concern during hemodialysis conducted with high-flux membranes. Novel hollow-fiber membranes were developed that had asymmetric convective solute transport properties, aimed at reducing the passage of potentially harmful molecules from dialysate to blood, while maintaining the desired fluid and solute movement from blood to dialysate. METHODS: Sieving coefficient as a function of molecular weight was measured in vitro using polydisperse dextrans. Measurements were conducted using two different flat-sheet membranes in series or using hollow fiber membranes having two integrally formed skin layers. Based on measured experimental parameters, model calculations simulated the performance of a clinical-scale dialyzer containing these new membranes versus that of a commercially available high-flux dialyzer. RESULTS: Asymmetric convective solute transport was demonstrated using both commercial flat-sheet and newly developed hollow-fiber membranes. For two flat-sheet membranes in series, the extent of asymmetric transport was dependent on the order in which the solution was filtered through the membranes. For the hollow-fiber membranes, the nominal molecular weight cut-off was 20 kD in the blood-to-dialysate direction and 13 kD in the dialysate-to-blood direction. For this membrane, model calculations predict that clearance of a beta2-microglobulin-sized molecule (11,800 D) would be significantly greater from blood to dialysate than in the reverse direction, even under conditions of zero net ultrafiltration. CONCLUSION: A novel hollow-fiber dialysis membrane was developed that allows greater convective solute transport from blood to dialysate than from dialysate to blood.

Increased protein loss during peritonitis associated with peritoneal dialysis is neutrophil dependent.

BACKGROUND: Peritonitis in peritoneal dialysis patients is accompanied by an enhanced migration of neutrophils (PMNs) and increased protein loss into the peritoneal cavity; however, the role of PMNs in governing increased protein loss during peritonitis associated with peritoneal dialysis is unknown. METHODS: We determined the importance of PMNs in governing changes in peritoneal permeability to protein in New Zealand White rabbits in which acute peritonitis was induced by adding 4 x 106 colony-forming units of Escherichia coli to 35 mL/kg of 0.9% saline dialysate. The total leukocyte and PMN migration into the peritoneal cavity was assessed by differential cell counts in the dialysate, and peritoneal permeability to protein was evaluated by calculating the dialysate to plasma concentration ratio for total protein as a function of time during a six- or eight-hour dwell. In series 1 experiments, leukocytes were depleted from the rabbit circulation by an intravenous injection of mustine (1.2 mg/kg) three days before the experiment; in series 2 experiments, integrin-dependent PMN migration into the peritoneal cavity was inhibited by an intravenous injection of monoclonal antibody (mAb) 60.3 (2 mg/kg) directed against the integrin CD18 on leukocytes five minutes before the experiment. RESULTS: In series 1 experiments, mustine decreased circulating leukocytes by 82 +/- 5% (mean +/- SEM) and circulating PMNs by 93 +/- 3%. Total leukocyte and PMN migration into the peritoneal cavity and peritoneal permeability to protein were decreased in mustine-treated rabbits after exposure to E. coli in the dialysate to levels similar to those found in rabbits without bacterial peritonitis. In series 2 experiments, an intravenous injection of anti-CD18 antibody also abrogated both the enhanced PMN migration into the peritoneal cavity and the increased peritoneal permeability to protein after exposure to E. coli in the dialysate. CONCLUSIONS: PMN migration into the peritoneal cavity is integrin dependent. Increased protein loss during acute, gram-negative bacterial peritonitis in a rabbit model of peritoneal dialysis is PMN dependent.

Solute fluxes in different treatment modalities.

The principles governing solute flux or transport in different artificial kidney treatment modalities are reviewed. Solute clearance profiles were calculated for identical artificial kidney membranes during haemodialysis, haemofiltration and haemodiafiltration. It was shown that the clearance of small solutes depends largely on the dialysate flow rate and is similar when using either haemodialysis or haemodiafiltration. In contrast, clearance of middle molecules, especially low-molecular-weight proteins, depends largely on convective transport induced by high ultrafiltration rates and is maximized when using either haemofiltration or haemodiafiltration. Optimal fluxes for both small solutes and middle molecules can be achieved by using postdilution haemodiafiltration. Recent work has shown that use of the reduction in plasma concentration, even after normalization for changes in extracellular volume during therapy, is not an exact measure of beta2-microglobulin (and other low-molecular-weight proteins) clearance. It is proposed that beta2-microglobulin clearance be reported in future studies instead of the normalized reduction in beta2-microglobulin plasma concentration. Additional studies are necessary to determine the effects of postdialysis rebound on the calculated clearance for beta2-microglobulin and other high-molecular-mass uraemic toxins.

Rebound kinetics of beta2-microglobulin after hemodialysis.

BACKGROUND: Evaluation of beta2-microglobulin (beta2m) removal during hemodialysis using predialysis and immediate postdialysis plasma concentrations is only valid in the absence of postdialysis rebound. Postdialysis rebound of beta2m has not been studied extensively, and its importance in the determination of beta2m clearance is unknown. METHODS: We evaluated the kinetics of urea and beta2m in a crossover study of 10 chronic hemodialysis patients using dialyzers with similar urea mass transfer-area coefficients containing either low-flux cellulose acetate or high-flux cellulose triacetate membranes. Kinetics were examined during and following a 210 minute treatment by measuring plasma concentrations predialysis at regular intervals during therapy and at 0, 2, 10, 20, 30, and 60 minutes postdialysis. Clearances of urea and beta2m were also determined directly from the arterial and venous concentration differences across the dialyzer at 60 minutes after starting dialysis. RESULTS: By design, urea removal was similar for both low-flux and high-flux dialyzers as assessed by the urea reduction ratio and Kt/V. Postdialysis urea rebound was similar for low- and high-flux dialyzers; the rebound in the plasma urea nitrogen concentration (expressed as a percentage of the intradialytic decrease in plasma concentration) was 9.2 +/- 1.9% (mean +/- SEM) at 30 minutes postdialysis and 13.0 +/- 1.4% at 60 minutes postdialysis for a single pool urea Kt/V of 1.16 +/- 0.05. The plasma beta2m concentration increased by 11.1 +/- 3.0% during the treatment using the low-flux dialyzer but decreased by 27.1 +/- 4.0% during the treatment using the high-flux dialyzer. When using the high-flux dialyzer, the rebound of beta2m was 44.8 +/- 21.4% at 30 minute postdialysis and 45.9 +/- 15.9% at 60 minutes postdialysis. The clearance of beta2m for the high-flux dialyzer calculated from predialysis and immediate postdialysis plasma concentrations using a single-compartment model (28.2 +/- 4.4 ml/min) was higher (P < 0.05) than that determined directly across the dialyzer (18.3 +/- 2.0 ml/min). If either the 30- or 60-minute postdialysis plasma beta2m concentration was used instead, the calculated beta2m clearance (16. 5 +/- 4.8 ml/min or 15.6 +/- 2.8 ml/min, respectively) was similar to that determined directly across the dialyzer. CONCLUSIONS: Postdialysis rebound of beta2m when using high-flux dialyzers is substantial; neglecting postdialysis rebound results in an overestimation of beta2m clearance when calculated using a single-compartment model.

Ultrafiltration method for measuring vascular access flow rates during hemodialysis.

BACKGROUND: The vascular access blood flow rate (QA) has been shown to be an important predictor of vascular access failure; therefore, the routine measurement of QA may prove to be a useful clinical method of vascular access assessment. METHODS: We have developed a new ultrafiltration (UF) method for determining QA during HD from changes in arterial hematocrit (H) after abrupt changes in the UF rate with the dialysis blood lines in the normal (DeltaHn) and reverse (DeltaHr) configurations. This method accounts for cardiopulmonary recirculation and requires neither intravenous saline injections nor accurate knowledge of the dialyzer blood flow rate. Clinical studies were conducted in 65 chronic HD patients from three different dialysis programs to compare QA determined by the UF method with that determined by saline dilution using an ultrasound flow sensor. RESULTS: Arterial H increased (P<0.0001) after abrupt increases in the UF rate when the lines were in the normal and reverse configurations. An increase in the UF rate from the minimum setting to 1.8 liter/hr resulted in a DeltaHn of 0.3+/-0.2 (mean +/- SD) H units and a DeltaHr of 1.6+/-1.0 H units. Q(A) values determined by the UF method (1050+/-460 ml/min) were 16+/-25% higher (P<0.001) than those determined by saline dilution (950+/-440 ml/min); the calculated QA values by the UF and saline dilution methods correlated highly with each other (R = 0.92, P<0.0001). The average coefficient of variation for duplicate measurements of QA determined by the UF method in a subset of these patients (N = 21) was approximately 10% when assessed in either the same dialysis session or consecutive sessions. CONCLUSIONS: The results from this study show that changes in arterial H after abrupt changes in the UF rate can be used to assess Q(A).

Hemodynamic monitoring during hemodialysis.

Intradialytic monitoring of hemodynamic parameters is an active area of research; future developments in this field will decrease intradialytic morbidity and the mortality of end-stage renal disease patients treated by hemodialysis. Recent investigations have been assisted by the development of devices that can continuously and noninvasively measure hematocrit and plasma protein concentration during the treatment. Intradialytic morbidity, fluid overload, and hypertension in chronic hemodialysis patients have been shown to be associated with either large or small intradialytic decreases in blood or plasma volume that can be routinely measured by these devices. The use of intradialytic changes in blood volume as a feedback control parameter to vary the ultrafiltration rate and dialysate sodium concentration, so called profiling, is now possible, but further research in this area is necessary to show how to optimize the control algorithms. Other, more preliminary studies suggest that monitoring of central blood volume, extracellular volume, and cardiac output during hemodialysis may permit improved hemodynamic stability during treatment and better control of blood pressure. Although optimal application of these techniques and devices remains to be shown, their routine use during maintenance hemodialysis therapy will likely be the standard of care in the near future.

Monitoring vascular access flow.

Blood flow in peripheral arterio-venous fistulae and grafts as used for hemodialysis access can be derived from measurements of the amount of access recirculation induced by reversing the dialysis blood lines and a knowledge of dialyzer blood flow rates. Furthermore, low or falling access blood flow rates are predictive of access dysfunction from the development of an intraluminal stenosis, which may be reversible, or of access thrombosis. The monitoring of access blood flow rates in hemodialysis populations is therefore suggested. Technologies including ultrasound dilution, hematocrit dilution (or concentration) differential conductivity, and thermodilution used for such monitoring are described.

Effect of permeability on indices of haemodialysis membrane biocompatibility.

BACKGROUND: Increases in plasma anaphylatoxins frequently are used as an index of haemodialysis membrane biocompatibility; however, their plasma levels may be influenced by the loss of anaphylatoxins into the dialysate compartment. METHODS: We compared the generation and compartmental distribution of anaphylatoxins, C3a and C5a, in a high flux and a low flux polysulfone membrane dialyser when whole human blood was recirculated through an in vitro haemodialysis circuit. RESULTS: Plasma C3a levels in high flux polysulfone (2.31 +/- 0.81 microg/ml) and low flux polysulfone (3.02 +/- 0.98 microg/ml) dialysers were comparable after 120 min (P = NS). In contrast, dialysate C3a in high flux polysulfone (0.65 +/- 0.31 microg/ml) accounted for 37.5 +/- 7.0% of the total detected (plasma + dialysate) C3a mass in the dialysers, while dialysate C3a in low flux polysulfone dialysers (0.01 +/- 0.01 microg/ml) accounted for only 0.3 +/- 0.3% of the total mass (P < 0.05; high flux vs low flux). Anaphylatoxin C5a was undetectable in the dialysate compartment of either dialyser examined. CONCLUSIONS: Our results indicate that anaphylatoxins readily traverse certain high flux dialysis membranes; consequently, plasma C3a levels may not accurately reflect the C3-activating potential of these membranes.

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.

Fluid state and blood pressure control in patients treated with long and short haemodialysis.

BACKGROUND: Patients treated at the haemodialysis (HD) centre in Tassin, France have been reported to have superior survival and blood pressure (BP) control. This control has been ascribed to maintenance of an adequate fluid state, antihypertensive drugs being required in < 5% of the patients, although it could not be excluded that a high dose of HD regarding removal of uraemic toxins might also have been of value. METHODS: The aim of the study was to assess the fluid state and BP in normotensive patients on long HD (8 h) in Tassin (group TN) using bioimpedance to measure extracellular volume (ECV), ultrasound for determining the inferior vena cava diameter (IVCD), and 'on-line' monitoring of the change in blood volume (BV), and to compare them with normotensive (group SN) and hypertensive (group SH) patients on short HD (3-5 h) at centres in Sweden. ECV was normalized (ECVn) by arbitrarily setting the median ECV (in % of body weight) in SN patients at 100% for each gender, recalculating the individual values and combining the results for male and female patients in each group. RESULTS: The dose of HD (Kt/V urea) was higher for TN patients than for Swedish patients who had a similar Kt/V, whether hypertensive or not. SH patients had significantly higher ECVn and IVCD than TN and SN patients. TN and SN patients did not differ significantly regarding ECVn and IVCD before and after HD. However, in a subgroup of eight TN patients, ECVn was below the range of that in SH and SN patients, due to obesity with a high body mass index. Another subgroup of 14 TN patients had a higher ECVn than most of the SN patients and also higher than the median ECVn in the SH group, without any difference in body mass index, but they were nevertheless normotensive. The fall in BV was greater in SN than in TN patients, presumably due to a higher ultrafiltration rate in SN patients. However, SH patients had a smaller change in BV than SN patients, presumably because their state of overhydration facilitated refilling of BV from the interstitial fluid. CONCLUSIONS: Normotension can be achieved independently of the duration and dose (Kt/V urea) of HD, if the control of post-dialysis ECV is adequate. However, this is more difficult to achieve with short than with more prolonged HD during which the ultrafiltration rate is lower, BV changes are smaller and intradialysis symptoms less frequent. The results in the subgroup of patients with high ECVn at Tassin suggest that normotension may also be achieved in patients with fluid overload provided that the dialysis time is long enough to ensure more efficient removal of one or more vasoactive factors that cause or contribute to hypertension.

Effect of dialysis membranes and middle molecule removal on chronic hemodialysis patient survival.

The type of dialysis membrane used for routine therapy has been recently shown to correlate with the survival of chronic hemodialysis patients. We examined whether this effect of dialysis membrane could be explained by differences in dialyzer removal of middle molecules using data from the 1991 Case Mix Adequacy Study of the United States Renal Data System. The sample analyzed included patients who had been treated by hemodialysis for 1 year or more, who were dialyzed with the 19 most commonly used dialyzers in 1991, and for whom delivered urea Kt/V could be calculated from predialysis and postdialysis blood urea nitrogen concentrations. Vitamin B12 (1,355 daltons) was used as a marker for middle molecules, and the clearance of vitamin B12 was estimated based on in vitro data. After adjustments for case mix, comorbidities, and urea Kt/V, the relative risk of mortality for a 10% higher calculated total cleared volume of vitamin B12 was 0.953 (P < 0.0001 v 1.000). Similar results were obtained when middle molecule removal was adjusted for body size. We conclude that both small and middle molecule removal indices appear to be independently associated with the risk of mortality in chronic hemodialysis patients. Differences in mortality when using different types of dialysis membrane may be explained by differences in middle molecule removal.

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group.

Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta2-microglobulin (beta2M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse.

Enhanced fluid removal guided by blood volume monitoring during chronic hemodialysis.

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2-7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 +/- 0.62 L (mean +/- SD) or 47 +/- 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 +/- 0.9 kg versus 2.0 +/- 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 +/- 5% versus 4 +/- 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.

Effect of hemodialyzer reuse: dissociation between clearances of small and large solutes.

Dialyzers are reused in approximately three quarters of the dialysis units in the United States, but the effect of reprocessing on dialyzer performance has not been extensively evaluated. In a crossover study of six chronic hemodialysis patients, we determined urea, creatinine, phosphate, and beta2-microglobulin clearances and dialysate protein loss for two types of low-flux and two types of high-flux dialyzers during use numbers 1, 2, 5, and 15. Dialyzers were reprocessed by an automated machine using Renalin (Renal Systems, Plymouth, MN) as the germicide. Dialyzer arterial and venous blood and dialysate outflow samples were obtained at 5 and 180 minutes of each dialysis session to evaluate solute clearances. Urea, creatinine, and phosphate clearances were calculated using dialysate concentrations, whereas beta2-microglobulin clearance was calculated using plasma concentrations to include its removal by adsorption to the dialysis membrane. There was a trend for urea, creatinine, and phosphate clearances to decrease with reuse for both low-flux and high-flux dialyzers, but these differences were not statistically significant. The clearance of beta2-microglobulin and dialysate total protein concentration was small for low-flux dialyzers; these values were not dependent on reuse. There was a trend for beta2-microglobulin clearance and dialysate total protein concentration to decrease during a dialysis treatment using high-flux dialyzers. More significantly, beta2-microglobulin clearance and dialysate total protein concentration decreased substantially with the reuse of high-flux dialyzers. These observations show that the maintenance of small solute clearances during reuse of high-flux dialyzers does not ensure the maintenance of large solute clearances.