Evaluating a new method to judge dialysis treatment using online measurements of ionic clearance.

New technology now supports direct online measurements of total dialysis dose per treatment, Kt. An outcome-based, nonlinear method for estimating target Kt in terms of ionic clearance measurements and body surface area (BSA) has been described recently. This is a validation study of the new method that evaluates the relationship between the (actual Kt-target Kt) difference and death risk. Patients with Kt measurements during March 2004 were identified (N=59,644). Target Kt was determined for each patient using the new method. Patients were then grouped by (actual Kt-target Kt) decile. They were also grouped by (actual URR-target URR) decile. Cox analysis-based risk profiles were constructed using those groupings. The (actual Kt-target Kt) difference profiles suggested improving death risk as Kt increased from below target to equal target. Risk ratios then flattened and remained so until (actual Kt-target Kt) reached the highest decile at which it appeared to improve, suggesting a possible biphasic profile. The (URR-target URR) risk profile was U-shaped. Death risk was related to the difference between the actual Kt and a target Kt value selected using the new nonlinear method. The method is therefore valid for prescribing and monitoring hemodialysis treatment.

Dedicated outpatient vascular access center decreases hospitalization and missed outpatient dialysis treatments.

Dedicated outpatient vascular access centers (VAC) specializing in percutaneous interventions (angiography, thrombectomy, angioplasty and catheter placement) provide outpatient therapy that can obviate the need for hospitalization. This paper reports the impact of one VAC staffed by interventional nephrologists on vascular access-related hospitalization and missed outpatient dialysis treatments. We performed a retrospective analysis of vascular access-related hospitalized days and missed vascular access-related outpatient dialysis treatments from 1995 to 2002 in 21 Phoenix Arizona Facilities (5928 cumulative patients) and 1275 cumulative Fresenius Medical Care North America (FMCNA) facilities (289,454 cumulative patients) to evaluate the impact of the introduction of a VAC in Phoenix. Vascular access-related hospitalized days/patient year and missed dialysis treatments/patient year declined from 1997 to 2002 across all access types. The decline was greater in Phoenix and coincided with the creation of a VAC in 1998. By 2002, there were 0.57 fewer hospitalized days/patient year and 0.29 fewer missed treatments/patient year than in the national sample (P<0.01). In 2002, the relative risk for vascular access hospitalized days was 0.38 (95% confidence interval (CI) 0.27-0.5) (P<0.01) and for vascular access-related missed outpatient dialysis treatments was 0.34 (95% CI 0.24-0.49) (P<0.01) in Phoenix vs FMCNA after adjustment for age, gender, diabetic status duration of dialysis and access type. VAC development was associated with a significant decrease in vascular access-related hospitalization and missed outpatient dialysis treatments. Further studies are necessary to demonstrate this effect in other communities.

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.

The effect of blood contact and reuse on the transport properties of high-flux dialysis membranes.

The effect of blood contact and reprocessing using bleach on the convective transport of both neutral and positively charged dextrans was determined for cellulose triacetate (CT), polyacrylonitrile (PAN), and polysulfone (PS) dialyzers (Fresenius USA, F60B, Concord, CA). For neutral dextrans, blood contact reduced the convective permeability, determined by differences in the sieving coefficient profile for both the PAN and PS, but not for CT dialyzers. Reprocessing of the dialyzers with bleach (up to 15 reuses) did not affect the convective transport of dextrans through CT or PAN, but did enhance the permeability of the blood contacted PS dialyzers. However, sieving coefficients for the blood contacted and reprocessed PS (F60B) dialyzers were significantly lower than those for the other dialyzers studied, approaching zero for dextrans larger than 18 k molecular weight. Sieving coefficients for positively charged, diethylaminoethyl (DEAE) dextrans were a function not only of solute size, but also of the membrane's capacity for adsorption of charged molecules. The majority of smaller, filtered DEAE dextrans adsorbed to the PAN membrane. Adsorption of DEAE dextrans to PAN was not observed for larger dextrans, or for DEAE dextrans of any size with CT, despite the lower permeability of both membranes for DEAE dextran compared to that for neutral dextrans.

Ultrafiltration and backfiltration during hemodialysis.

Ultrafiltration is the pressure-driven process by which hemodialysis removes excess fluid from renal failure patients. Despite substantial improvements in hemodialysis technology, three significant problems related to ultrafiltration remain: ultrafiltration volume control, ultrafiltration rate control, and backfiltration. Ultrafiltration volume control is complicated by the effects of plasma protein adsorption, hematocrit, and coagulation parameters on membrane performance. Furthermore, previously developed equations relating the ultrafiltration rate and the transmembrane pressure are not applicable to high-flux dialyzers, high blood flow rates, and erythropoietin therapy. Regulation of the ultrafiltration rate to avoid hypotension, cramps and other intradialytic complications is complicated by inaccurate estimates of dry weight and patient-to-patient differences in vascular refilling rates. Continuous monitoring of circulating blood volume during hemodialysis may enable a better understanding of the role of blood volume in triggering intradialytic symptoms and allow determination of optimal ultrafiltration rate profiles for hemodialysis. Backfiltration can occur as a direct result of ultrafiltration control and results in transport of bacterial products from dialysate to blood. By examining these problems from an engineering perspective, the authors hope to clarify what can and cannot be prevented by understanding and manipulating the fluid dynamics of ultrafiltration.

Pathways for fluid loss from the peritoneal cavity.

During peritoneal dialysis, fluid is transported out of the peritoneal cavity by lymphatic and nonlymphatic pathways, thereby decreasing net ultrafiltration by 40-50% and reducing small solute clearance by 15-20%. The direct lymphatic pathway consists of the diaphragmatic lymphatics, which directly connect the peritoneal cavity to the bloodstream. The interstitial lymphatic and direct blood entry pathways convey fluid that has been driven into the interstitial space of the tissue surrounding the peritoneal cavity by the increased intraperitoneal pressure, and return it to the bloodstream. Since flow through lymphatic pathways is only a portion of the flow through all pathways, total fluid loss is greater than lymph flow. The best technique for estimating lymph flow is direct measurement by cannulation of lymphatic vessels, a technique that is not clinically feasible. The tracer disappearance technique, which measures the rate at which macromolecules leave the peritoneal cavity, is an indirect measure of fluid loss. The tracer appearance technique, which measures the rate at which macromolecules reach the blood from the peritoneal cavity, slightly overestimates lymph flow because some tracer may enter the bloodstream directly from the tissues. Much of the previous controversy over the contribution of the lymphatic pathways to total fluid loss can be resolved by understanding the differences in what these techniques measure.

The effect of hemoglobin concentration on peritoneal mass transfer and drain volumes in continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine whether a correlation exists between hemoglobin levels and peritoneal mass transfer or drain volumes in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective study of two groups of CAPD patients, identified on the basis of their stable hemoglobin levels. Group A--hemoglobin less than 8.5 g/dL; Group B--hemoglobin greater than 10.5 g/dL. Peritoneal mass transfer and drain volumes were measured for each patient, after which a subgroup of Group A was treated with rHuEPO (forming Group C) and measurements repeated once hemoglobin had risen by at least 2.0 g/dL. SETTING: Single renal unit of a university teaching hospital. PATIENTS: Twenty-seven patients established on CAPD, selected according to their stable hemoglobin level. Group A--14 patients; Group B--13 patients; Group C (subgroup of A)--8 patients. MAIN OUTCOME MEASURES: Difference between peritoneal mass transfer or drain volume in Group A versus Group B, and in Group C before and after rHuEPO therapy. Serum biochemical parameters in Group C before and after rHuEPO therapy. RESULTS: No statistically significant differences in any of the parameters measured were found between groups A and B, or before and after rHuEPO therapy in Group C. CONCLUSIONS: Peritoneal transfer of small solutes and water is not influenced by hemoglobin level, and does not change following otherwise effective treatment with rHuEPO.

Effect of high hematocrit and high blood flow rates on transmembrane pressure and ultrafiltration rate in hemodialysis.

Removal of prescribed ultrafiltration volumes in hemodialysis requires knowledge of both the ultrafiltration coefficient of the dialyzer and the average transmembrane pressure (TMP) in the dialyzer. While it has been a fairly common practice to assume that the TMP is constant along the length of the dialyzer, it actually decreases linearly from a maximum value at the blood inlet to a minimum value at the blood outlet. In the past, ignoring the difference between arterial and venous TMPs when calculating the dialysate pressure setting did not result in significant errors in ultrafiltration volume. However, with the introduction of erythropoietin therapy and the trend toward high-efficiency dialysis, increases in hematocrit and blood flow rate have led to axial variations in TMP which, if ignored, can lead to inaccurate fluid removal. The goals of this paper are to provide an understanding of how high hematocrits and high blood flow rates affect TMP and ultrafiltration rate, and to provide simple guidelines for ensuring accurate fluid removal. Sample calculations are given on the last page for easy reference.