High blood flow rates with adjustment of needle diameter do not increase hemolysis during hemodialysis treatment.

BACKGROUND: Higher blood flow in dialysis therapy is often avoided due to concerns about shear-induced blood damage despite the lack of reliable data. OBJECTIVE: This study investigated the influence of higher blood flow rates on plasma free hemoglobin (Hb) concentration after hemodialysis (HD) treatment. METHODS: Thirty-two chronic HD patients were treated once with a blood flow rate of 250 mL/min using a 17G needle, and once with a blood flow rate of 500 mL/min using a 14G needle. Arterial and venous pressure and blood pressure (BP) were recorded before and after treatment. Blood samples were taken before and after treatment for analysis of plasma free Hb, pH, HCO3, base excess, hematocrit value, urea, sodium, potassium and calcium. RESULTS: HD treatment at blood flow rates of 500 mL/min did not increase plasma free Hb compared to treatments at blood flow rates of 250 mL/min. Frequency of intradialytic BP drops was not different either. By adaptation of the needle size, negative arterial pressure could be kept at a similar level. Urea reduction rates were significantly higher during treatments with higher blood flow rates. CONCLUSION: Higher blood flow rates can be applied without an increased hemolysis risk provided that needle sizes are adapted accordingly.

Digestive-absorptive function of the intestinal brush border in uremia.

Amino acid absorption was studied in chronic uremic rats. Intestinal transport of L-leucine appears to be inhibited with mild uremic intoxication, whereas severe uremia enhances absorption. Brush border activity of intestinal maltase and disaccharidases is higher in rats with chronic renal insufficiency. The same holds for gamma-glutamyl-transpeptidase activity.

Options in dialysis therapy: significance of cardiovascular findings.

Most patients receiving renal replacement therapy have cardiovascular disease. The most frequent conditions are left ventricular hypertrophy and coronary artery disease. Hemodialysis is associated with a characteristic spectrum of acute complications (such as hypotension, sudden death) that can be explained by typical dialysis-induced effects on the heart. With continuous ambulatory peritoneal dialysis (CAPD) some of those cardiovascular complications are ameliorated due to slow ultra-filtration and absence of an arteriovenous fistula. It is concluded that CAPD might be the preferable option in patients with cardiovascular disease when hemodialysis can only be performed in a standardized and often aggressive manner. However, achievement of medically-defined goals appears to be more important than technique in dialysis therapy.

Gastrointestinal blood loss in patients undergoing maintenance dialysis.

Gastrointestinal blood loss was measured for 14 days in 19 patients treated by hemodialysis and in 2 patients treated by chronic ambulatory peritoneal dialysis. 51Cr was used as a marker for erythrocytes. Fecal blood loss was 5.0 +/- 3.3 ml/day in hemodialysis patients who were not taking drugs affecting thrombocyte aggregation and 4.6 +/- 4.3 ml/day in those receiving sulfinpyrazone. There was no relationship between the severity of anemia, duration of dialysis, dose of heparin, grade of uremic intoxication, or dose of aluminum hydroxide and amount of fecal blood loss. It is concluded that gastrointestinal blood loss is not a major determinant of anemia in chronic renal failure. However, sulfinpyrazone is preferable to acetylsalicylic acid for prevention of shunt thrombosis in uremic patients because of their propensity for gastrointestinal bleeding.

Therapeutic effects of short-term plasma exchange in endogenous uveitis.

We studied the effects of plasma exchange in nine patients with endogenous uveitis and in one patient with Behçet's syndrome (a total of 15 episodes of uveitis). Topical or systemic drug therapy, which was begun four to 12 weeks before admission, was continued throughout the entire study period of five weeks. Plasma exchange was carried out in four sessions during a one-week period. In each patient a total of 12 liters of plasma was removed and replaced by a 3% human albumin electrolyte solution. Immediately after the plasma exchange period there was a reduction of cellular infiltration of the anterior chamber and vitreous body in all injured eyes. In 21 of 30 instances there was complete remission of inflammatory activity for the control period of 18 months after four plasma exchange sessions. All patients had improved visual acuities. The only side effect was incompatibility reactions to human albumin in two cases.

Organic nitrate therapy in glaucoma.

We determined the effect of organic nitrates on normal volunteers and patients with open-angle and narrow-angle glaucoma. Nitroglycerin lowered intraocular pressure in all patients when administered by the perfusion technique. Isosorbide dinitrate given orally (2 x 40 mg per day) has a potent decreasing effect on intraocular pressure, which cannot be explained by the influence on arterial blood pressure.

Regular dialysis treatment in Germany: the role of non-profit organisations.

Germany's healthcare system is almost entirely premium-funded through compulsory insurance. Doctors practicing in an outpatient setting are obliged to be members of the "Kassenarztliche Vereinigung" (KV), a kind of union for physicians that has to guarantee adequate medical care for all insured patients. Health money is transferred from health insurances to KV and then distributed to individual doctors. In 1998, 47,000 patients were treated in Germany by dialysis, 40% in privately-owned units, 22% in hospital units and 40% by non-profit facilities. Of these, 35% have diabetes mellitus, 50% of the patients new to dialysis. A total of 92% are treated in HD units, 1.5% at home, and 6.7% by PD. Not-for-profit organisations were founded in 1969 to overcome the shortage of dialysis facilities. These organisations provide all the non-medical components of dialysis therapy such as machines, disposables, buildings, employment, and management of staff. Nephrologists who are employed by or work with not-for-profit organisations are free to choose the best medical therapy, with no economic bias. Assessment of dialysis quality is not yet official in Germany and it is not clear whether there are different provider associated outcomes.

A prospective randomised European multicentre study of medium-long run mortality and morbidity comparing acetate-free biofiltration and bicarbonate dialysis.

In recent years, the progressive increase in the mean age of the population entering chronic dialysis treatment has been responsible, on the one hand, for the growing number of patients undergoing regular dialysis, and on the other, for the high number of "critical" patients, both as a result of their age and the presence of concomitant morbidity. Thus, dialysis treatment today is not only aimed at waste removal and water-electrolyte homeostasis, but also at a reduction in morbidity and mortality, and at improving the patients' quality of life, thanks to the use of biocompatible materials and the achievement of good cardiovascular tolerance to treatment. Consequently, diffusive-convective dialysis procedures have been on the increase, since they combine better depuration with the use of biocompatible high-flux membranes. Acetate-free biofiltration (AFB) is a diffusive-convective dialysis procedure which utilises a high-flux membrane, AN69, post-dilution infusion of a sodium bicarbonate solution (NaHCO3), and a dialysate which is completely free of any buffer, and thus also free of acetate, which may have various negative effects on the patient. A number of studies have already shown the better hemodynamic stability and the reduction of intradialytic side-effects during AFB. All these, however, were short-term studies. To verify the beneficial effects of AFB in the long run, a three year multicentre randomised European trial has been proposed to compare bicarbonate hemodialysis (BD), a technique used in nearly 80% of the world's dialysis population, and AFB. The specific aim of the investigation is to verify, in a large number of patients, the results of hemodialysis treatment in terms of morbidity, mortality and quality of life. The study involves 80 hemodialysis units across Italy, France, Germany, Spain, Slovenia and Croatia, with enrollment of about 400 patients considered "critical" for at least one of the following reasons: age, diabetes, dialysis cardiovascular instability. Fifty percent of the patients are to undergo AFB with the AN69 membrane and bicarbonate solution infusion (NaHCO3 145 or 167 mEq/lt), and the other fifty percent are to be treated by BD, with any membrane except the nonmodified cellulosic one. Biochemical, cardiological, and nutritional parameters will be considered throughout the study. Mortality, morbidity both in terms of intra- and interdialysis symptoms - and hospitalisation rate, as well as the patients' quality of life, evaluated by the SF36 questionnaire, will be analysed.

Simultaneous hemofiltration/hemodialysis: an effective alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients.

Hemofiltration and hemodialysis were performed simultaneously with the Polyacrylnitrile membrane in a single pass dialyzate flow system. Due to the combination of convective mass transfer and diffusion, the clearances of both small and large molecules were significantly higher than during hemofiltration or hemodialysis alone. The removal of excess water was better tolerated than during hemodialysis. Six patients have been treated by this technique for 6 months 3 X 3 hr/week without side effects, and the new procedure appears to be the method of choice to shorten dialysis time.

Asymmetric septal hypertrophy and left atrial dilatation in patients with end-stage renal disease on long-term hemodialysis.

Some literature reports associate a reduced weekly duration of treatment (3 x 4 h/week) for patients on maintenance hemodialysis with an increased cardiovascular mortality. To determine whether the improved survival of patients on long weekly hemodialysis (LHD: 3 x 8 h/week) can be associated with different cardiac changes, the cardiac characteristics of a group of 50 patients on LHD were analyzed in a non-invasive assessment. The main findings were an increased left ventricular (LV) muscle mass (176 + 54 g/m2), mass/volume ratio (1.69 + 0.37 g/ml) and left atrial diameter (39.7 + 5.7 mm). The increase in LV muscle mass was due mainly to a high prevalence of asymmetric septal thickening. The ratio septum/LV posterior wall was directly correlated with the left atrial diameter (r = 0.52), LV end-diastolic diameters were inversely correlated with hemoglobin concentration (r = 0.62). LV dilatation and/or LV systolic dysfunction were not characteristic findings: Only 6% of patients had a moderately enlarged (less than 65 mm) LV diameter, LV ejection fraction was decreased in 12%. There was no significant correlation between the degree of LV hypertrophy or left atrial dilatation and patient age, total dialysis duration, interdialytic weight gain, hemoglobin concentration, parameters of blood purification, blood pressure before and after dialysis, history of hypertension. We conclude that cardiac characteristics in patients on LHD are comparable to those described for large patient groups on short hemodialysis. Our findings do not explain improved survival on LHD.

Abnormal diastolic left ventricular filling by pulsed Doppler echocardiography in patients on continuous ambulatory peritoneal dialysis.

To determine characteristics of diastolic left ventricular (LV) function in patients on continuous ambulatory peritoneal dialysis (CAPD), two groups of CAPD patients without (n = 23; group 1) vs with (n = 25; group 2) LV hypertrophy (greater than 13 mm) were compared with a group of untreated non-renal hypertensive patients with LV hypertrophy (n = 11; group 3) using Doppler-echocardiography. Age and body surface area were comparable in all three groups, mean CAPD-duration (32 +/- 28 vs 26 +/- 23 months; p = NS) was comparable in renal patients. LV systolic function in echocardiography (LVEF: 62 vs 64 vs 63%) and systolic time intervals were normal and comparable in all three groups. Atrial maximum filling velocities (96 +/- 25 vs 91 +/- 25 vs 67 +/- 8 cm/s) were comparably increased, the ratio of maximal early/atrial filling velocities was comparably decreased (0.73 +/- 0.25 vs 0.77 +/- 0.21 vs 0.99 +/- 0.05) in both groups of renal patients as compared to group 3 (p less than 0.05-0.01). Atrial filling fractions were increased in all three groups, more pronounced in group 1 than in group 3 (50 +/- 11 vs 40 +/- 7%; p less than 0.05). The normal correlation of Doppler parameters with age and with LV radius/thickness ratio was altered in renal patients such that high patient age tended to have an additional negative influence on LV diastolic function of hypertrophied, but not of normal myocardium. Isovolumic relaxation time was prolonged in all three groups (134 +/- 38 vs 131 +/- 34 vs 116 +/- 17 ms; p = NS). We conclude that in patients on CAPD, diastolic LV filling is impaired both in normal and hypertrophied myocardium. High age is a factor that further attributes to diastolic dysfunction of hypertrophied myocardium in CAPD.

Ultrashort hemodiafiltration: efficiency and hemodynamic tolerance.

During hemodiafiltration, solutes are removed simultaneously by diffusion and convection. Increase of the fraction removed by diffusion, by using large surface area hemodiafilters, allows a further reduction of treatment time by hemodiafiltration. To assess the efficiency and biochemical safety of ultrashort treatment (mean duration 3 X 105 +/- 14 min/week) six patients (age 22-64) have been observed for six months. There were no differences in the clinical state or in the biochemical parameters compared to those found during the preceding hemodialysis period (3 X 240 min/week). In a second study, hemodynamic measurements in six individual patients aged 34-72 have been compared during a 90 min ultrashort hemodiafiltration (90 min) and during a 240 min hemodialysis. Circulatory stability was maintained during hemodiafiltration despite a rate of fluid removal that was 2.5 times that which occurred during hemodialysis. During both techniques there was a reduction of stroke volume and an adequate norepinephrine-induced rise of peripheral resistance. Plasma levels of vasopressin did not change during treatment. There were no differences in the frequency and quality of premature ventricular beats between the two treatments. The data from the two studies suggests that ultrashort hemodiafiltration (3 X 1.5-2 hr/week) provides biochemical safety as well as hemodynamic stability.

Influence of fluid removal rate during hemodialysis on left ventricular performance and exercise tolerance in patients with coronary artery disease.

The effect of hemodialysis (HD) on left ventricular (LV) function and exercise tolerance were measured at rest and during exercise using gated equilibrium radionuclide ventriculography in seven patients with confirmed coronary artery disease (CAD). To separate the effects of fluid removal rate on LV function in CAD, we investigated the same patients with identical overall volume loss of 4 liters during two different treatment times (4 hr and 2 hr). HD significantly increased resting LV ejection fraction (EF) from 55.7 +/- 8% to 64.7 +/- 8% (P less than 0.01) during the 4 hr HD and from 58.1 +/- 9 to 68.1 +/- 10 (P less than 0.05) during the 2 hr HD. Indicating ischemia, EF decreased at pre- and postdialysis peak exercise without differences between both treatments. HD also resulted in an improved segmental wall motion score. Exercise duration as well as S-T segment depression and angina score improved during HD, whereas heart rate, blood pressure and double product remained unchanged. We conclude that HD improves global and regional resting LV function and exercise tolerance in patients with CAD. The degree of interdialytic hydration and not the degree of fluid removal per time affects LV performance in CAD. Since LV function is the major prognostic factor in CAD, those patients require volume restriction and/or shorter interdialytic phases.

Extracorporeal pressure monitoring and the detection of vascular access stenosis.

Prospective monitoring of static venous pressure is an established tool to detect outflow stenoses in a vascular access. However, with this method it is not possible to identify vascular stenoses which are localized between the arterial and venous dialysis needle. We describe a new approach based on both static arterial and venous extracorporeal pressures. Pressure data of 9 dialysis patients with normal vascular access function and 9 patients with stenotic access were analyzed. Extracorporeal pressure was found to depend on the position of the heart relative to the extracorporeal blood circuit. All patients with venous outflow stenoses had an elevated ratio of arterial and venous intra-access pressure to mean arterial pressure. In case of access stenosis between arterial and venous needle the ratio of venous pressure to mean arterial pressure was normal, and only the arterial pressure ratio was elevated. We conclude that combined arterial and venous intraaccess pressure measurement normalized by mean blood pressure detects venous stenosis as well as stenosis between the arterial and venous dialysis needle. To minimize the rate of access thrombosis both arterial and venous intra-access pressure should be monitored.

Efficacy of membrane filtration, influence on hemostasis, immunoglobulins and inflammation mediators during daily plasma exchanges.

Plasma exchange (PE) by membrane filtration was performed with the following hollow fibers: cellulose-diacetate (Plasmaflo 01, Plasmaflo 02, Asahi, Japan), polypropylene (Plasmaflux, Fresenius, FRG) and polymethylmethacrylate (Plasmax, Toray, Japan). The elimination-coefficient (EC) for certain plasma proteins was calculated. With all hollow fibers no correlation between the EC for about ten plasma proteins with a molecular weight of 54.000 dalton up to 2.400.000 dalton. The mean EC-values for the fibers studied were: 0.32 (Plasmaflo 01), 0.52 (Plasmaflo 02), 0.52 (Plasmaflux) and 0.58 (Plasmax). Membrane filtration performed with the single needle technique using either Plasmaflo 02 or Plasmaflux resulted in a significantly lower efficiency with mean EC-values of 0.33 and 0.32 respectively. After three or four days of PE treatment using three liters of 3% human albumin solution as replacement fluid several alterations in parameters of hemostasis were altered: Antithrombin III levels dropped to 35% of normal value after each plasma exchange but increased to normal range within 24 hours during the observed period of four consecutive PE, Fibrinogen concentration dropped permanently to a preexchange value of 40% of the initial concentration after three plasma exchanges. A 40-50% decrease was also observed for prothrombin, plasminogen and alpha-2-macroglobulin after plasma exchange. A decrease in the platelet count ranging from 5 to 25% after each plasma exchange was observed but returned to the initial level before the next treatment. The concentrations of IgG IgA and IgM decreased to less than 20% of preexchange values and C 3 and C 4 to 20-30: of preexchange values after three plasma exchanges.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic pressure measurement for detection of blood access stenosis.

A novel method for detection of access failure has been developed. It is based on the continuous evaluation of pre-pump arterial and venous pressure in the extracorporeal circuit. Knowing the flow resistance properties of the arterial and venous branches of the extracorporeal circuit from in-vitro measurements and the height differences, calculating the fistula pressure dynamically is possible. The fistula pressure allows identification of access failure as has been shown by other authors. The dynamic measurement however allows identification of bad needle placement. Dynamic measurement at different flow rates and comparison with static measurements allow for the identification of intra-access stenosis. The mathematical algorithm is described and pressure-flow curves for two sets of extracorporeal circuits are shown. In-vivo examples show a "normal" fistula and a fistula with intra-access stenosis.

[Coronary risk factors in chronic hemodialysis patients]. / Koronare Risikofaktoren bei chronisch hämodialysierten Patienten.

BACKGROUND: In contrast to persons with normal renal function, coronary risk factors or indicators until yet could not clearly be defined in renal insufficiency. PATIENTS AND METHODS: 30 patients under chronic hemodialysis therapy were investigated; 15 patients with severe coronary artery disease and 15 patients with normal coronary angiogram were compared. Numerous factors of the manner of living (diet, smoking behaviour etc.) were registered and glucose and lipid metabolism, hemostatic and fibrinolytic system as well as blood pressure level were investigated. RESULTS: Besides higher HDL-cholesterol and tissue plasminogen activator (TPA) levels in patients without coronary heart disease, no significant difference could be found between both groups. The higher HDL levels were mainly due to the higher percentage of women in the coronary healthy group. There was no evidence of insulin resistance as a major pathogenic factor in the group with coronary heart disease. The blood pressure levels were not significantly different in both groups. CONCLUSION: Our quantitative examination of accepted or suspected coronary risk factors revealed no entity which turned out to be a reliable risk indicator for practical purposes.

Evaluation of maintenance of stable haemoglobin levels in haemodialysis patients converting from epoetin or darbepoetin to monthly intravenous C.E.R.A.: the MIRACEL study.

BACKGROUND AND OBJECTIVES: C.E.R.A., a continuous erythropoietin receptor activator, offers once-monthly dosing without compromising haemoglobin control. This study was undertaken to examine whether monthly C.E.R.A. using pre-filled syringes maintains stable haemoglobin levels when administered according to local clinical judgement. RESEARCH, DESIGN AND METHODS: MIRACEL was a prospective, open-label, single-arm, multicentre study performed at 90 nephrology centres in Germany. After a 2-month screening phase, haemodialysis patients receiving epoetin or darbepoetin were converted to monthly intravenous C.E.R.A., with a 5-month titration phase followed by a 2-month evaluation phase. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00413894 RESULTS: Of 661 patients screened, 424 (64.1%) started C.E.R.A. therapy (previous treatment: 72.2% epoetin, 27.8% darbepoetin); 416 were eligible for inclusion in the intent-to-treat population. A mean of two C.E.R.A. dose changes were required during the 7-month treatment period. The primary efficacy variable, haemoglobin within 11-12.5 g/dL or 10-13 g/dL during the evaluation phase, was achieved in 109 (30.8%) and 265 (74.9%) of the 354 evaluable patients, respectively, with no differences observed between patients formerly receiving epoetin or darbepoetin or different dosing frequencies. During the screening, titration and evaluation phases, mean haemoglobin was 11.7 +/- 0.7 g/dL, 11.6 +/- 0.9 g/dL and 11.4 +/- 1.0 g/dL, respectively, and 90.6% (377/416), 70.4% (293/416) and 82.9% (345/416) of patients exhibited < or = 1 g/dL change from phase-specific individual means. C.E.R.A. was well-tolerated with a safety profile similar to that reported in phase III studies. CONCLUSIONS: In this single-arm, open-label, multicentre study, conversion of a large population of haemodialysis patients from epoetin or darbepoetin to monthly C.E.R.A. administration using pre-filled syringes was shown to be practical, convenient and offer good control of haemoglobin levels, regardless of the previous type of therapy or dosing frequency.