Evaluation of health and quality of life in apheresis patients - data from the WAA register.

OBJECTIVE: The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. MATERIAL AND METHODS: Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. RESULTS: Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. CONCLUSION: Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma.

BACKGROUND AND OBJECTIVES: Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a-(desArg) after transfusion of autologous plasma with high content of C3a-(desArg). MATERIAL AND METHODS: Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a-(desArg), C3d,g, iC3), and soluble terminal complement complex (sC5b-9) were investigated. C3a-(desArg) kinetics was investigated in regular apheresis donors. RESULTS: Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a-(desArg), C3d,g and sC5b-9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a-(desArg)-levels were above the reference value in 88% of all components. After re-infusion of autologous plasma with high C3a-(desArg) content, there were rapid a(1) and a(2)-distribution followed by a slower b-elimination phase. CONCLUSION: Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a-(desArg) present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.

Minimized weight gain between hemodialysis contributes to a reduced risk of death.

UNLABELLED: The risk of death is higher in dialysis patients compared to age matched healthy subjects, the main reason being cardiovascular. This prospective study investigated if the extent of ultrafiltration was of importance for the outcome. MATERIAL AND METHODS: 88 hemodialysis patients were included and followed prospectively. The outcome was registered in regard to death, acute myocardial infarction or coronary vascular intervention. The extent of ultrafiltration needed at dialysis was calculated as a mean during the observation period as were other variables. The mean extent of ultrafiltration was compared for patients who had survived without end-points (group 1, n=53) versus those who reached any end-point during the period (group 2, n=35). RESULTS: In total, 40% of the patients reached end-point during the observation period. There was no difference at baseline between the groups in regard to age, prevalence of diabetes mellitus or history of previous cardiovascular disease, KT/V, residual renal function ultrafiltration need, C-reactive protein, s-albumin, cholesterol, LDL-cholesterol, HDL-cholesterol, appetite or wellbeing, while triglyceride was lower in group 2 (p=0.035). The observation period for group 1 was at a mean 24.7 months (SD13.1) and for those in group 2 at a mean 13.8 (+/-11.7 months, p<0.001). Patients representing group 1 at 24 and 30 months had less need of ultrafiltration than those in group 2. Thus, the need of ultrafiltration was about 27% lower at 24 months (for 29 persons in group 1: 3.63+/-1.93 weight% versus 4.97+/-1.70 weight% for 9 patients from group 2, p=0.046) and 46% at 30 months (for 18 from group 1: 3.48+/-1.95 versus 6.45+/-1.55 for 3 from group 2, p=0.030). C-reactive protein did not differ significantly between the groups during the period. CONCLUSION: After a prolonged period of 24 months the extent of ultrafiltration need seems to be important for the outcome of the patients. Thereby those with higher need of ultrafiltration had worse prognosis. It seems important to motivate patients to reduce the extent of fluid intake between dialysis to prolong survival.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction.

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Elderly patients on haemodialysis have 50% less functional capacity than gender- and age-matched healthy subjects.

OBJECTIVE: Patients on haemodialysis (HD) are by necessity inactive for 3-6 h three times a week. The aim of this prospective controlled study was to investigate the level of functional capacity of elderly HD patients using simple measures. MATERIAL AND METHODS: A total of 11 consecutive HD patients aged > 60 years (median age 75 years) were included in the study. They were compared with 22 gender- and age-matched healthy subjects using a prospective 1:2 case:healthy subject study design. As tests of functional capacity and maximal exercise capacity we used a "sit-to-stand" test (number of cycles within 10 s) and a staircase test (the number of cycles completed per second was used as the effect variable), respectively. RESULTS: The patients managed significantly fewer cycles than the healthy subjects in the staircase test (median 2 vs 10; p<0.003) and performed approximately 50% fewer cycles in the sit-to-stand test (p<0.014). The work performed in a given time in the staircase test was 54% less for the patients (p<0.017). CONCLUSIONS: The HD patients in the study had a considerably lower functional capacity than the healthy subjects, which may have interfered with their daily living activities. The tests used are easy to apply and need no specialized equipment. The importance of investigating functional capacity and instituting rehabilitation programmes is emphasized.

World apheresis association--world apheresis registry.

In 2002 WAA decided to start a world-wide apheresis registry to gain insight into the extent of treatment, adverse events, and to facilitate contacts among centers when treatment indications are rare and experience limited. Stem cell and other blood products collections intended for therapeutic application can also be entered. The WAA planned to use the French Registry. Its translation into English has not been accomplished and the fiscal obligations for that registry has not, as yet, been determined or considered and approved by the WAA Board. From Dec 2002 the proposed registry (a merged version of the French, Canadian and Swedish registries) can be immediately implemented. We now cordially invite all centers to join that registry. Please, also inform colleagues at other centers in your country to join. E-mail and address lists of colleagues in your country who have not registered will be welcomed. The site is at: Go to World Apheresis Registry; Login code to test the Registry is: al61tms. Then apply for a specific login code for your center. We welcome you to this registry for your input of data. You will not be charged any registration fee. The registry includes a randomization system that can be used for local or multi center studies (randomization by in-center basis allows you to make your own studies). It includes a formula that increases the chance to get a more even distribution between groups also for smaller sample sizes.

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study.

OBJECTIVE: There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). MATERIAL AND METHODS: The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. RESULTS: Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was 20%. Atorvastatin was withdrawn in 20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. CONCLUSIONS: Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

Blood lines conduct leakage current during haemodialysis: a potential safety risk during first failure, especially for patients with central dialysis catheter as access.

Haemodialysis (HD) machines are IEC-classified as I type B. When central dialysis catheters (CDCs) are used for access, there will be close electrical contact with the heart. To investigate the risk for HD patients, the leakage of current through the tubing set was measured during in vitro dialysis performed according to the IEC 60601-1 standard for class I cardiac floating (CF) devices. A series of eight measurements were made with Gambro GFS + 12 dialysers, first with saline and then with blood in the blood lines. The leakage current exceeded the CF limit (50 microA) at the top of the CDC using the test 'mains on applied part' for saline (median 1008 microA, range 720-1241 microA), for blood (median 610 microA, range 449-772 microA) and also for a 'single fault condition' using saline (median 68 microA, range 35-118 microA) or blood (47 microA, range 4-128 microA). In the single fault condition, the highest leakage current at the CDC (128 microA) almost exceeded the earth leakage current in normal conditions. A safety risk can appear if a single fault arises in the dialysis machine or another device connected to the same patient, or during 'mains contact to the patient'. Then the current flow may be high enough to induce arrhythmias in the patient, especially when a CDC is used. These data and the use of CDCs as access for dialysis indicate that HD machines should be classified as cardiac floating rather than body (B) devices.

Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients.

BACKGROUND: [corrected] Patients on hemodialysis often have a moderate hypertriglyceridemia in combination with low HDL cholesterol. A contributing factor may be a derangement of the lipoprotein lipase (LPL) system. During dialysis, with heparin as anticoagulant, the enzyme is released into the circulating blood. METHODS: We have followed LPL activity and triglycerides during ordinary heparin administration in nine hemodialysis patients and controls matched for age and gender. Blood samples were drawn before heparin administration and at 15, 30, 60, 120, 180 and 240 min. RESULTS: LPL activity peaked at 15 or 30 min and then decreased to a plateau that was only 20%, of the peak. The activity was reduced in the patients by about 50% during the peak, and about 20% during the following plateau. During the peak of lipase activity the triglycerides decreased in both groups, but the change was less pronounced in patients, as was expected from the lower circulating lipase activity. During the plateau phase with low lipase activity, the triglycerides increased towards baseline values. CONCLUSIONS: During hemodialysis with heparin, there is a peak in LPL activity as well as a reduction in triglycerides during the first hour. Thereafter LPL activity decreases towards a plateau, while triglycerides increase towards baseline. The peak activity of LPL in the patients was only half that in controls, while the plateau was comparable. The data indicate that during and following each dialysis there is a period when LPL activity becomes depleted to a level that is limiting for normal lipoprotein metabolism.

Renal abnormalities in a population of patients with psoriatic arthritis.

OBJECTIVE: To investigate the prevalence of and to identify predictive factors for renal abnormalities in patients with psoriatic arthritis (PsA). METHODS: 73 patients with PsA were consecutively examined by laboratory analyses and clinically for joint manifestations. Renal function was estimated by creatinine clearance and urinary albumin. RESULTS: 17 (23.3%) of the patients had renal abnormalities as defined by creatinine clearance below the lower cut off of normal distribution (mean - 2 SD) and/or urinary excretion of albumin more than 25 mg/24 h. These patients were significantly older at the time of the study, older at joint disease onset, had longer skin disease duration, increased serum levels of beta2-microglobulin, and higher incidence of increased ESR and/or CRP levels. Increased ESR/CRP levels had significantly predictive value in multivariate analysis. CONCLUSIONS: In this study subclinical renal abnormalities was a prevalent finding. Predictive factor was inflammatory activity measured by laboratory variables. There were no predisposing effects of NSAID or DMARD therapy.

Lipoprotein lipase during continuous heparin infusion: tissue stores become partially depleted.

Lipoprotein lipase (LPL) and hepatic lipase (HL) are located at vascular surfaces in extrahepatic tissues and in the liver, respectively. Heparin displaces the enzymes into the circulating blood. Animal studies have shown that the liver takes up and degrades LPL. To explore whether heparin leads to a depletion of tissue stores, we followed the lipase activities in plasma during an 8-hour primed infusion of heparin in 10 healthy subjects. After an initial peak, the HL activity decreased slowly after a time curve similar to that for activated partial thromboplastin time. The time curve for LPL was different. After the initial peak, the activity dropped by almost 80%, from 30 to 120 minutes, and then leveled off to a plateau that corresponded to about 15% of the peak level. A second bolus of heparin was given to 4 subjects after 4 hours. The plasma LPL activity increased, but only to about 35% of the original peak level. We conclude that when heparin releases LPL into plasma, the lipase becomes liable to be taken up and degraded by the liver. After less than 1 hour, the stores of LPL have been exhausted, and recruitment of lipase into plasma depends on a slow but stable delivery of newly synthesized molecules.

Apheresis registry in Sweden: scope, techniques and indications for treatment. A report from the Swedish apheresis study group.

Registries of therapeutic apheresis can be used to evaluate changes in technology, clinical indications and applications over the years. This study reports data collected prospectively and voluntarily in Sweden during 1993-1999. A total number of 40 apheresis units have been performing therapeutic apheresis procedures: 16 blood centers, 20 dialysis units, two intensive care units, one hematology ward and one hemotherapy unit. The registry includes a median of 92%) of the centers for therapeutic apheresis in Sweden during the years and in 1999 there were 31 active units in 26 hospitals. The total numbers of procedures per year have remained fairly stable corresponding to a median of 46 treatments/ 100,000 inhabitants, and in 1999 4084 procedures were performed. The number of plasma exchanges has decreased, but LDL-apheresis and immunoadsorption procedures have increased over the years. 70% of the patients have been referred for 12 indications. A significant decline was found for patients with SLE and Guillain Barres syndrome. The use of extracorporeal photo-chemotherapy has increased over the years, and 3 indications include >75$ of the patients. There has been an adaptation to the experience learned by different studies. The number of collections of hematopoietic progenitor cells is about 9/100,000 inhabitants, and in 1999 821 collections were performed. The use of allogeneic donors is increasing. The extent of therapeutic apheresis in Sweden was compared to other countries on the basis of published data. In Sweden, the extent of therapy is two- to three-fold to that for Canada and France.

The presence of superantigens and complex host responses in severe sepsis may need a broad therapeutic approach.

Patients with sepsis can progress into septic shock, disseminated intravascular coagulation, and multiorgan dysfunction syndrome. Various materials secreted by or released from microorganisms such as bacteria initiate these processes. In some bacteria, certain antigens and toxins may cause a 100-fold greater or supernormal activation of monocytes and T lymphocytes, leading to activation of the cascade systems in the host. This can explain the extremely rapid progress of the sepsis into septic shock seen in some patients. In Group A streptococci, more than 100 different toxins have been identified, about 5 of which (superantigens) cause an extremely fast immunological response. Because the toxins and antigens can activate so many different cascade systems in the host, the clinical picture is extremely complex, and little benefit is derived from therapy, which interferes with only 1 or 2 of the parameters in the patient with sepsis. Instead, reversal of the septic shock requires the removal or inhibition of several toxins or substances activating the cascade systems. A broader therapeutic approach may be the use of apheresis (plasma exchange).

Apheresis as therapy for patients with severe sepsis and multiorgan dysfunction syndrome.

Progressive multiorgan dysfunction syndrome may occur in the course of sepsis and septic shock as well as after various intoxications, pancreatitis, crush injuries, and major surgery. Despite conventional intensive care therapies, the prognosis in these patients is still poor. Apheresis, which uses more selective adsorption techniques, can lower the extent of toxins and cytokines in blood. This is achieved in clinical practice by, e.g., using polymyxin B as adsorbent. Although significantly lowered, the mortality is still about 50% with this technique. By unselective plasma exchange, the mortality is reduced down to 20 to 40%. A controlled and randomized study has shown a significant benefit. The centrifugation technique may be favorable over plasma filtration. Not only removal but also replacement with plasma seems important. In the future, probably selective techniques will be used in the early stages of sepsis while unselective plasma exchange may be useful in a disseminated situation.

Electrical current leakage during hemodialysis may increase blood-membrane interaction.

UNLABELLED: During hemodialysis blood - membrane interaction causes complement activation. During dialysis there may be an electrical current leakage to the dialyzer, especially if there is a broken ground or a defect in another electrical device coupled to the patient. This study investigated whether an electric current of 1.5 mA DC could alter blood membrane interaction as measured by changes in C3d in the blood. Such a high current leakage could occur because there is no protection in the dialysis machine (Class 1B) against auxiliary current leakage. Such a current could come from a defective external device in contact with the patient during hemodialysis. MATERIALS: A dialysis machine (Fresenius 2008C) with a filled blood-line system containing about 350 ml whole blood from each of 8 different donors was used in vitro. Each of the eight test-runs also contained 1000 U added heparin. The dialysis procedure was performed using hemophan membranes (GFS + 12, Gambro) with bicarbonate and potassium 3.0 (D210, Gambro) as dialysate. Two electric poles were placed in the blood line, before and after the dialyzer (connected in parallel) and the ground was placed at entry and exit of the dialysate fluid coming from the machine to the dialysis filter. C3d was measured before the start of "dialysis" and at 15, 30, 45 and 60 min, during dialysis. Thereafter the 1.5 mA current was switched on and additional samples were drawn at 75 and 90 min. The mean C3d values were calculated. Paired non-parametric statistical analyses were performed. RESULTS: There was a significant and continuous increase in C3d as compared to the "predialysis" level. The increase during 0 to 30 minutes was greater than that from 30 to 60 minutes (p=0.018); the increase in C3d during 60 to 90 min, was greater than that from 30 to 60 min (p=0.018) and there was no difference between the 0 to 30 and the 60 to 90 min increases. CONCLUSIONS: A current, used in this study, was able to induce a blood membrane interaction during in vitro dialysis. Even a weaker current leakage might have such adverse effects and similar interactions seem possible during regular dialysis depending on the extent of the leakage.

Current leakage in hemodialysis machines may be a safety risk for patients.

During hemodialysis, the dialysis fluid is conductive and allows current to flow from or to the machine if a difference in electrical potential occurs. This may cause a health risk for the patient. We investigated the presence of such current during various conditions in 17 dialysis machines: the Gambro AK10 (n = 5) and AK100 (n = 3), and the Fresenius 2008C (n = 3), 2008E (n = 2), and 4008E (n = 4). Current leakage measurements were performed without connection of the patient to the system by using a copper tube inserted into the stream of the dialysis fluid at the point where the patient would normally be connected to the dialyzer. The current leakage (measured in microA) at the ground site was significantly higher for the AK10 and the 2008C than for the AK100, 2008E, and 4008E machines. The current leakage, at the site where the dialyzer is located, was highest for the AK10 and less for the AK100, 2008C, 2008E, and 4008E. The 2008C and 2008E dialyzers had the highest maximal current leakage when a malfunctioning external device was attached while the AK100 had less and the AK10 had the least leakage. There was a great variation in leakage current among the dialysis machines. The greatest risk occurred when the patient also was connected to other electric devices with current leakage.