Clinical outcomes of hemodialysis patients in a public-private partnership care framework in Italy: a retrospective cohort study.

BACKGROUND: Innovative care models such as public-private partnerships (PPPs) may help meet the challenge of providing cost-effective high-quality care for the steadily growing and complex chronic kidney disease population since they combine the expertise and efficiency of a specialized dialysis provider with the population care approach of a public entity. We report the five-years main clinical outcomes of a population of patients treated on hemodialysis within a PPP-care model in Italy. METHODS: This descriptive retrospective cohort study consisted of all consecutive hemodialysis patients treated in the NephroCare-operated Nephrology and Dialysis unit of the Seriate Hospital in 2012-2016, which exercises a PPP-care model. Clinical and treatment information was obtained from the European Clinical Database. Hospitalization outcomes and cumulative all-cause mortality incidences that accounted for competing risks were calculated. RESULTS: We included 401 hemodialysis patients (197 prevalent and 204 incident patients) in our study. The mean cohort age and age-adjusted Charlson Comorbidity Index were 67.0 years and 6.7, respectively. Patients were treated with online high-volume hemodiafiltration or high-flux hemodialysis. Parameters of treatment efficiency were above the recommended targets throughout the study period. Patients in the PPP experienced benefits in terms of hospitalization (average number of hospital admissions/patient-year: 0.79 and 1.13 for prevalent and incident patients, respectively; average length of hospitalization: 8.9 days for both groups) and had low cumulative all-cause mortality rates (12 months: 10.6 and 7.8%, 5 years: 42.0 and 35.9%, for prevalent and incident patients, respectively). CONCLUSIONS: Results of our descriptive study suggest that hemodialysis patients treated within a PPP-care model framework received care complying with recommended treatment targets and may benefit in terms of hospitalization and mortality outcomes.

Rare presentation of endometrial carcinoma with singular bone metastasis.

The major symptom at diagnosis of endometrial cancer is post-menopausal bleeding; it is present in around 90% of cases. Singular bone metastasis is described as an uncommon site for endometrial cancer at diagnosis, showing in just 5-6% of cases. In this report we describe a rare presentation of a singular bone metastasis because of endometrial cancer of a woman with previous diagnosis of early breast cancer. A review of literature uncovered some cases of bone metastasis at presentation of endometrial cancer and that it can occur as first symptom of cancer before vaginal bleeding. This rare presentation of uterine cancer needs to be studied and described because it may be seen and needs a homogeneous treatment to improve survival.

[Anticoagulation and chronic hemodialysis]. / Anticoagulazione ed emodialisi cronica.

The application of effective hemodialysis in humans was delayed until the development of cellulose-based membranes in 1940s, and the advent of heparin as the primary means of anticoagulation. Unfractionated heparin is still the most commonly used agent for anticoagulation, but its potentially serious complications, such as hemorrhage and heparin-induced thrombocytopenia type II, led the scientific community to consider other options to counteract coagulation. ''Low heparin dialysis'', ''heparin-free dialysis'', regional heparinization, low molecular weight heparins, citrate, prostacyclin, nafamostat, low molecular weight heparanoid and direct thrombin inhibitors are among these methods and have different safety, efficacy and cost. In general, hemodialysis patients with active hemorrhage or at high risk for bleeding complications are best treated with heparin-free hemodialysis. Low molecular weight heparanoid and direct thrombin inhibitors (recombinant hirudin or argatroban) may be useful for anticoagulation of the extracorporeal circuit in the rare patients with confirmed heparin-induced thrombocytopenia type II, who cannot be dialyzed with heparin.

[Convective and mixed dialysis technique]. / Le tecniche dialitiche miste convettive-diffusive.

Hemodiafiltration is the dialytic strategy enabling the high potential of hydraulic and solute permeability of synthetic membranes to be most properly exploited, thus greatly enhancing removal of small and middle-molecular toxic compounds. Several of those solutes have a pathogenic role or are recognized as marker of the most frequent long-term complications and causes of death in HD patients, such as dialysis related amyloidosis, cardio-vascular disease, secondary hyperparatyroidism, inflammation and malnutrition. Improved survival in dialysis has been associated, in observational studies, with the use of high-flux membranes and hemodiafiltration with high volume exchange. On-line production of unlimited amount of sterile dialysate at low cost has favored its extensive diffusion in the recent years, and optimal biocompatibility of synthetic high-flux membranes and the quality of the ultrapure dialysate have contributed to the promising results of the technique. However, to optimize its clinical application and achieve safely the most efficient convective transport, knowledge is required of dialysis systems, dialyzer characteristics and performances, and of the complex interactions between patient and membrane. New hemodiafiltration techniques have been proposed in these years with the aim to improve the efficiency and safety of the technique. More generally, technical aspects and requirements, and experimental and clinical results of the convective-mixed treatments are examined here.

[Census of the Italian Nephrology and Dialysis Units. Comparison between Lombardy and Piedmont]. / Censimento 2004 Centri di Nefrologia e Dialisi. Confronto tra Piemonte e Lombardia.

The Italian Society of Nephrology promoted a national survey to obtain detailed information from all the Renal and/or Dialysis Units through an on-line questionnaire concerning structural, technological and human resources, as well as organisation characteristics and activities. The purpose of this initiative was to obtain regional reference benchmarks for each Nephrology Unit. In this paper we compare two northwestern Italian Regions: Lombardy and Piedmont. As far as epidemiology is concerned, the prevalence of dialysis patients is quite similar in the two Regions: for haemodialysis 616 pmp (patients per million population) in Lombardy and 595 in Piedmont, for peritoneal dialysis 104 pmp vs. 114 pmp, while the incidence of dialysis patients is 169 vs. 166 pmp. The gross mortality for dialysis patients is 12.4% vs. 13.7% and 0.9% vs. 2.0% in transplanted patients. The distribution of vascular access is also quite similar in the two Regions: prevalent arteriovenous fistula 83% vs. 74%, central venous catheter 11% vs. 18%, vascular grafts 7% vs. 8%. Structural resources: the hospital beds (49 pmp in the two Regions) and the dialysis places (161 vs. 166 pmp) do not differ between the two Regions. Personnel resources: physicians 37 pmp in Lombardy and 44 pmp in Piedmont, renal nurses 167 pmp vs. 186, respectively. Activity: hospital admission 1722 pmp vs. 1507 pmp, renal biopsies 131 pmp vs. 109 pmp. Although the two regions examined are numerically different, both have a high standard of quality, making Italy a model of nephrology organisation. This initiative to take a census of the Italian Nephrology and Dialysis Units provides an interesting tool to describe the present status of the operational structures, to identify precise benchmarking values, at both the regional and national level, and to act as a prelude for further rationalization and growth of the nephrology network in Italy.

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

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

[Guidelines on water and solutions for dialysis. Italian Society of Nephrology]. / Linee Guida su acque e soluzioni per dialisi.

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

[Italian study on the treatment of anaemia in chronic dialysis patients switched over to less frequent doses of darbepoetin from human recombinant erythropoietin (rHuEPO)]. / Studio italiano sul trattamento dell'anemia in pazienti in terapia dialitica sostitutiva con darbepoetina alfa con una minore frequenza di somministrazione della dose rispetto all'eritropoietina ricombinante umana (rHuEPO).

BACKGROUND: Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin (rHuEPO), including a three-fold longer elimination half-life that allows for less frequent dosing. This study was aimed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO. METHODS: Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha. Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha. Patients received darbepoetin alpha by the same route of administration (SC or IV) as the one used for rHuEPO. The unit doses of darbepoetin alpha (10-150 microg) were titrated to maintain haemoglobin concentration within -1.0 and +1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks. RESULTS: The mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was statistically but not clinically significant [-0.10 g/dL (95% CI: -0.18, -0.02]. In general, the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [(from 26.10 micro g/wk to 25.90 microg/wk; percentage change -0.40% (95% CI: -3.78, 3.10)]. Overall, darbepoetin alpha was well tolerated. CONCLUSIONS: The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency.

The effect of transient intestinal ischemia on inflammatory parameters.

BACKGROUND AND AIMS: To determine the early biological changes occurring in intestinal ischemia in vivo. PATIENTS AND METHODS: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. RESULTS: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28+/-3.4 pg/ml (preischemic) to 109+/-85.9 pg/ml (ischemic) and to 189.33+/-120.24 pg/ml (reperfusion); and tromboxane B(2) levels from 141.57+/-51.20 pg/ml preoperation to 473.01+/-319.01 pg/ml during the surgical procedure. CONCLUSION: These observations indicate that even transient ischemia modifies the inflammatory pattern.

Effects of the infusion mode on bicarbonate balance in on-line hemodiafiltration.

BACKGROUND: Electrolyte and acid-base balance may be differently affected by the infusion mode in on-line hemodiafiltration (HDF). We studied the effects of the different infusion modes on bicarbonate transport across the dialyzer membrane, and thus on the final bicarbonate balance of the HDF sessions. METHODS: Instantaneous HCO3- transfer across the dialyzer membrane, blood bicarbonate profile and the total balance of the sessions were studied in six dialysis patients under the same operating conditions over 36 HDF sessions, in order to compare the effects of predilution HDF (pre-HDF), postdilution HDF (post-HDF), and mixed HDF on the final bicarbonate balance. RESULTS: The final HCO3- balance was more positive in post-HDF vs pre-HDF (142 +/- 36 vs 99 +/- 41 mmol/session, p<0.05), with a final blood HCO3- concentration of 26.6 +/- 1.0 vs 25.4 +/- 1.1 mmol/L, (p<0.05). Mixed HDF yielded intermediate results (balance: 119 +/- 42 mmol/session, final HCO3- 26.2 (1.2 mmol/L). These differences were seen to result from the increased HCO3- concentration of blood entering the filter in predilution, due to the infused HCO3-, enhancing convective loss and reducing the driving force for diffusive HCO3- gain. CONCLUSIONS: Bicarbonate concentration in dialysate-reinfusate is critical in order to obtain an adequate end of session HCO3- balance in on-line HDF. The predilution method produced the lowest cumulative net HCO3- gain between the three studied infusion modes. Our data suggest that, under the same operating conditions and excluding the effect of ultrafiltration, dialysate HCO3- should be increased by about 2 mmol/L in pre-HDF, and 1 mmol/L in mixed HDF, to yield the same final balance as in post-HDF.

Rate dependence of acute PTH release and association between basal plasma calcium and set point of calcium-PTH curve in dialysis patients.

BACKGROUND: In vivo, the control of calcium-mediated acute PTH release during induced hypo- or hypercalcaemia is linked not only to plasma calcium concentration per se but also to the rate and direction of calcium change. In fact, during induced hypocalcaemia, the predominant mechanism that causes PTH to be released is the reduction of plasma Ca(2+) irrespective of the absolute starting concentration of ionized calcium. This mechanism, which is rate-dependent and even activated in conditions of hypercalcaemia, may be involved in the association, reported in several papers, between the basal Ca(2+) and the set point of the calcium-PTH curve. METHODS: The calcium-PTH relationship was studied in 12 dialysis patients under conditions of induced low and high predialysis plasma Ca(2+). At each level of basal Ca(2+), dynamic tests were conducted using two methodological approaches. In method A patients underwent low (0.5 mmol/l) calcium dialysis in the stimulation test and high (2 mmol/l) calcium dialysis in the inhibition test, while the dialysate calcium (CaD) was kept constant during each test. In this way a higher but variable rate of change in plasma Ca(2+) was achieved. In method B, CaD was progressively decreased (stimulation test) and increased (inhibition test) during the tests in order to obtain a lower but more constant rate of change in plasma Ca(2+). Consequently, for each patient, four calcium-PTH curves were produced: low basal Ca(2+) with methods A and B, and high basal Ca(2+) with methods A and B. RESULTS: Basal plasma Ca(2+) was similar in A and B at low (1.16+/-0.02 vs 1.15+/-0.02 mmol/l) and high (1.25+/-0.02 vs 1.26+/-0.02 mmol/l) basal plasma Ca(2+). The set point was higher in A than in B both at low (1.12+/-0.02 vs 1.10+/-0.02 mmol/l, P=0.01) and high (1.20+/-0.02 vs 1.16+/-0.02 mmol/l, P=0.03) basal Ca(2+) as was the slope (542+/-41 vs 426+/-44%/mmol, P=0.02; 615+/-73 vs 389+/-25%/mmol, P=0.01). No significant difference was found between A and B as regards minimal PTH and plasma Ca(2+) at minimal PTH (Camin) in both calcaemic states. Maximal PTH was slightly higher in B at low (510+/-97 vs 548+/-107 pg/ml, P=NS) and high basal plasma Ca(2+) (410+/-97 vs 464+/-108 pg/ml, P=0.02). Plasma calcium at maximal PTH (Camax) was significantly higher in A (1.1+/-0.03 vs 0.99+/-0.02 mmol/l, P=0.001) at high basal plasma Ca(2+). The set point was strictly related to basal plasma Ca(2+) in both methods, but the slope of the linear regression was significantly steeper with method A. The set point was predicted to increase by 0.881 (CI 0.772-0.990) mmol/l for each mmol/l of increase in basal plasma Ca(2+) with method A and by 0.641 (CI 0.546-0.737) mmol/l for each mmol/l of increase in basal plasma Ca(2+) with method B. CONCLUSIONS: (i) Higher and variable rates of change in plasma Ca(2+) produce a higher set point value and a steeper slope of the calcium-PTH curve when compared to lower and more constant rates of calcium change. (ii) The different slope of the linear correlations between basal plasma Ca(2+) and set point in the two methods suggests that the rate-dependent mechanism of acute PTH release plays a significant role in the association between set point and basal plasma Ca(2+). (iii) The significance of the set point is questionable when the calcium-PTH curve is carried out in vivo.

Evaluation of thrombogenicity of fluoropassivated polyester patches following carotid endarterectomy.

The use of a patch after carotid endarterectomy (CE) is recommended to reduce the incidence of restenosis. Most studies on this subject report the implantation of saphenous vein or PTFE patches, because polyester has always been considered to be a thrombogenic material. The purpose of this study was to evaluate the thrombogenicity of a knitted polyester patch passivated by fluoropolymer surface treatment (FPD patch), which experimental studies have demonstrated to be less thrombogenic than other materials. This prospective, randomized study was performed in 22 patients who underwent CE. In 11 patients the arteriotomy was sutured directly, while in the other 11 an FPD patch was applied. Patients' 111in-oxine labeled platelets were reinjected on the first postoperative day, and scintigraphies were performed after 4, 24, and 48 hr, respectively. The study confirmed that an FPD patch is no more thrombogenic than a simple carotid endarterectomy. The application of the patch, therefore, can be recommended to reduce restenosis without any adjunctive thromboembolic risk.

Mixed predilution and postdilution online hemodiafiltration compared with the traditional infusion modes.

BACKGROUND: On postdilution hemodiafiltration (post-HDF), convective removal of medium-high molecular weight solutes is, at the highest ultrafiltration rates, limited by high blood viscosity and protein concentration. Prefilter reinfusion (pre-HDF) may overcome this problem, but plasma dilution may affect the overall efficiency of the technique. In this study, an experimental system of online HDF with combined prefilter and postfilter infusion (mixed HDF) was evaluated and compared with the traditional predilution and postdilution modes. METHODS: Removal of urea (U), creatinine (Cr), phosphate (Phos), and beta(2)-microglobulin (beta(2)m), ultrafiltration coefficients of the dialyzer (K(UF)), and rheologic conditions of the blood circuit were evaluated during the three infusion modes (a total of 36 runs lasting 180 min), performed with a polysulfone hemofilter 1.8 m(2), blood flow (Q(b)) 400 mL/min, dialysate flow (Q(d)) 700 mL/min, and infusion rate 120 mL/min (pre-HDF and post-HDF), or 60 + 60 mL/min (mixed HDF). RESULTS: The mean effective U and Cr clearances and urea index of dialysis dose (eKt/V) were significantly higher on post-HDF than on pre-HDF (K(WB) (U) 210 vs. 193 mL/min, K(DQ) (Cr) 152 vs. 142 mL/min, eKt/V 1.41 vs. 1.30), while mixed HDF did not show significant differences versus post-HDF (K(WB) (U) 201 mL/min, K(DQ) (Cr) 149 mL/min). K(DQ) for Phos and beta(2)m were higher on post-HDF in only absolute values. Similar differences were found for instantaneous dialyzer clearances (K(I)) at 60, 120, and 180 minutes of the sessions, with a common trend to decrease with time. K(UF) and the apparent beta(2)m sieving coefficient showed their lowest values toward the end of post-HDF sessions. Increasing filtration fractions (FFs) were associated with increasing transmembrane pressure (TMP) and solute clearances up to FF values of 0.45. These were values achieved in only post-HDF, at which point the curve of the relationship between TMP and FF assumed its steepest exponential trend. CONCLUSIONS: Mixed HDF, by better preserving the characteristics of water and solute transport of the membrane, ensured safer operating conditions than post-HDF, while achieving similar removal of small- and large-size solutes. Optimizing the ratio of prefilter/postfilter infusion and the total infusion according to the relationships found in our study between solute clearances, FF, and TMP, convective flux and transport may avoid excessive hemoconcentration and dangerous pressure gradients.

Effect of high-flux dialysis on the anaemia of haemodialysis patients.

BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.