Identification of complement activators and elucidation of the fate of complement activation products during extracorporeal plasma purification therapy.

It has been known for many years that the complement system is activated during extracorporeal plasma purification (ECCP) therapy. In a previous study, we showed that high concentrations of complement activation products (CAPs) are returned to the patient during immunoadsorption treatment. In the present study, we investigated the question of where complement activation takes place with different forms of ECPP equipments as well as the fate of the CAPs. Eleven patients (8 men and 3 women), mean age 52 +/- 18 years, were included in the study. They were treated either with plasmapheresis (PP), immunoadsorption, bilirubin adsorption, or low density lipoprotein (LDL) apheresis. It was found that during all ECPP treatments and after the plasma separation filter, the plasma concentrations of CAPs were increased, and that high concentrations of CAPs were returned to the patients, except with PP. The plasma levels of individual CAPs varied between different types of ECPP. These variations were due to several factors: (1) complement activation (CA) on the plasma separator and a secondary device, e.g., column or membrane; (2) adsorption of specific CAPs to separation columns; and (3) reduction of CAPs due to separation and waste. Since CAPs have inflammatory and immunological effects, it is possible that high serum concentration of CAPs in the treated patients may influence the clinical outcome of the treatment. In conclusion, complement activation is a fact that should not be ignored during performance of any form of an ECPP. It is the plasma separator that plays a key role in the process of complement activation. Different ECPP treatments may have different effects regarding the levels of individual CAPs.

Plasmapheresis in HLA-immunosensitized patients prior to kidney transplantation.

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

Acute renal failure and outcome of continuous arteriovenous hemodialysis (CAVHD) and continuous hemofiltration (CAVH) in elderly patients following cardiovascular surgery.

A total of 111 elderly patients from the cardiac surgery intensive care unit (ICU) with acute renal failure (ARF) were studied during a period of 7 years (1988-1994). Forty-two patients being operated for coronary bypass (CBP) (31 M, 11 F), 26 patients for valve replacement (VR) (18 M, 8 F), 20 patients for a combined operation of coronary bypass and valve replacement (CBP+VR) (14 M, 6 F) and 23 patients for resection of aneurysm of the abdominal aorta (ROAOAA) (11 M, 12 F). Average age of the patients was 70 +/- 4 yr (65-80). Their blood pressure on the first day of continuous renal replacement therapy (CRRT) was 75 +/- 19 mmHg (50-95) and was maintained at about 95 +/- 15 mmHg (70-120) by using vasopressor drugs. From the results of this study a survival of 38% was registered within the CBP group, 65% within the VR group, 45% within the CBP+VR group and 91% within the ROAOAA group. The overall survival in all of the patients was 58%. It was a high mortality (62%) within CBP group compared to that of 35%, 55% and 9% within the VR, CBP+VR and ROAOAA groups, respectively. This is because more patients with predisposing preoperative risk factors, e.g., hypertension (33%) and Diabetes (17%) etc were found in the CBP group, in addition to their post operative complications of which bleeding necessitating reoperations was encountered in 31%. Multiple organ failure (MOF) was a common major problem of which respiratory failure needing artificial ventilation was encountered in about 90% of the patients. The overall mortality was 42% in which the major cause of death was MOF/circulatory failure. Heart failure was the second cause of death. Other secondary complications, e.g., liver failure (n = 6) and atrial fibrillation (n = 11) etc. might have added to the high mortality in this study. The effect of CRRT on uremic control was measured by following-up of the daily levels of the serum urea and creatinine and a steady-state uremic control was achieved. We conclude that CRRT can be considered as a reliable artificial renal support for ARF in ICU elderly patients.

Treatment of acute renal failure in intensive care patients by continuous arteriovenous hemofiltration (CAVH): two years' experience in two centres.

The study objective was to evaluate the outcome of continuous arteriovenous hemofiltration (CAVH) as a first choice treatment for acute renal failure (ARF) in critically ill intensive care patients in two centres with a long experience in the field of continuous renal replacement therapies. Sixty consecutive intensive-care ARF patients from Uppsala Centre and 71 consecutive ARF patients from Vicenza Centre were included during a period of two years. Their age range was 58 +/- 16 and 52 +/- 15 years in Uppsala and Vicenza, respectively. CAVH was performed in the postdilution form using different types of hemofilters. Three choices of vascular access were utilised in each centre, namely: the Buselmeier shunt, femoral vessel catheter and the Scribner shunt. The pre-treatment serum urea level (mean +/- SD) in the Uppsala patients (30 +/- 14 mmol/l) was significantly higher (p < 0.001) than that of the Vicenza patients (17 +/- 10 mmol/l). The Uppsala patients had a longer treatment duration than the Vicenza patients; 8 +/- 6 vs 5 +/- 5 days (p < 0.05) perhaps because they were much older than the Vicenza patients (p < 0.05) in addition to their multi-organ failure. However, the total outcome of CAVH in the two centers was not significantly different (52 and 58% patient's survival in Uppsala and Vicenza, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous peritoneal dialysis in children with acute renal failure.

Continuous peritoneal dialysis (CPD) was performed in 13 children with acute renal failure (ARF) in our intensive care units (ICU). The median age was 6 months (range 3 days to 77 months). Sixty-nine percent of the patients (9/13) were below the age of 12 months. CPD was performed for a median duration of 5 days (range 1-35 days). In 62% of the patients (8/13), the cause of ARF was acute tubular necrosis (ATN) due to cardiac surgery. The outcome of CPD regarding total survival was 54% (7/13). A high mortality was registered (83% of the deaths [5/6]) within the first year of life, which suggests a worse prognosis if ARF occurs at this age. Half of the total deaths (3/6) were among the cardiac surgery patients. Peritoneal equilibration tests (PET) were performed utilizing measurement of urea and glucose transport through the peritoneal membrane at short intervals during a period of 45-60 min from the start of treatment. Short dwell times of 5-20 min were found to be sufficient for adequate uremic control until a satisfactory daily urine production was noted. CPD is a useful and simple treatment modality for ARF in critically ill ICU children. Equilibration tests are useful and should be considered for optimization of CPD treatment in critically ill children with ARF in order to achieve the goal of controlling uremia and fluid overload, and giving nutritional support.

Complement activation during tryptophan immunoadsorption treatment.

Antibodies against human lymphocyte antigens (HLA) are frequently seen among patients undergoing repeated renal transplantations. Graft survival can be improved by eliminating these antibodies by plasmapheresis before transplantation. In this study, we have tried a new extracorporeal procedure to remove the anti-HLA antibodies. An immunoadsorption column (IM-TR) with a matrix of polyvinyl alcohol (PVA) gel conjugated with a hydrophobic amino acid tryptophan was utilized. Previous results have shown that repeated IM-TR treatments are at least equally effective as plasmapheresis in reducing levels of specific immunoglobulins in treated patients. In this study, 7 HLA-immunized patients were treated before renal transplantation. Each patient was subjected to a total of 12 treatment sessions divided into 3 sessions per week. After each treatment session, the reduction of the immunoglobulins was less than what has been reported for plasmapheresis. This suggests that mechanisms other than immunoglobulin depletion are involved in the reduction of the total immunoglobulin levels. The IM-TR treatment resulted in a strong complement activation triggered by the alternative pathway. Since the adsorbed plasma was returned to the patient, exceedingly high levels of the activation fragment C3d (C3dg) were found in plasma during and after the treatment. We conclude that the extensive generation of C3dg may be one of the factors that plays a role in the reduction of the antibody levels since the C3dg fragment has been shown to down-regulate the immune response.

Pretransplantation immunoadsorption therapy in patients immunized with human lymphocyte antigen: effect of treatment and three years' clinical follow-up of grafts.

Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post-transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation.

Continuous arteriovenous hemodialysis: outcome in intensive care acute renal failure patients.

The clinical outcome of continuous arteriovenous hemodialysis (CAVHD), an alternative to continuous arteriovenous hemofiltration (CAVH) in our intensive care units (ICU) in Uppsala, was evaluated for 2 years. Forty-three patients were included. Pretreatment serum urea and creatinine levels (mean +/- SD) were 36 +/- 13 mmol/l and 420 +/- 147 mumol/l, and during treatment, steady-state levels were 25 +/- 10 mmol/l and 333 +/- 120 mumol/l, respectively (p < 0.0001). On top of acute renal failure (ARF), some patients had multiple organ failure that made it necessary to use mechanical respiration (63%), vasopressor drugs (74%) and aortic balloon pump therapy (5%). The outcome of this treatment was 60% when overall survival was considered. Higher dialysate flow rates (i.e., 25 ml/min) were applied in some patients in whom serum urea levels were persistently rising. The result of this was a notable decrease in the urea and creatinine serum levels. From the results of this 2-year experience, we have found CAVHD a promising alternative to CAVH that can be used as a treatment of choice for ARF in critically ill ICU patients.

Continuous arteriovenous haemodialysis and haemofiltration in intensive care acute renal failure patients.

CAVHD and CAVH were compared regarding uraemic control in 13 critically ill intensive care patients with acute renal failure (ARF). Patients' mean age was 60 years. Pretreatment blood urea range was 17-56 mmol/l (33-56 mmol/l in 70% of the patients). All patients received vasopressor drugs, and 92% were on artificial mechanical respiration. From the results of this study both modalities gave adequate uraemic control. There was a notable decrease in the urea and creatinine levels with CAVHD more than with CAVH. There was no statistically significant difference between the two modalities in the urea clearance. However, a significant difference (P < 0.05) in creatinine was obtained with CAVHD. Our results suggest that CAVHD is a useful alternative to CAVH in ARF especially when the blood urea level is > 30 mmol/l. However, a higher dialysate flow rate (e.g. 25 ml/min) should be used if the urea level is more than 40 mmol/l. CAVH should be reserved for ARF patients in whom fluid overload is a major problem.

Artificial renal and liver support in a severe hepatorenal syndrome of childhood.

This case report describes a special management approach in a child aged 4.5 years with a severe form of hepatorenal syndrome in which the final diagnosis was familial hemophagocytic lymphohistiocytosis (FHL). The patient presented with grade IV hepatic coma and acute renal failure (ARF). While the diagnosis was difficult at the time of admission, as well as during acute treatment, artificial liver support was established for elimination of bilirubin and other metabolic by-products by using charcoal column plasma perfusion (CCPP) and bilirubin-adsorbing resin column plasma perfusion (BRCPP). Serum levels of bilirubin showed a notable decrease after each of the four treatment sessions. Additional artificial renal function replacement by continuous arteriovenous hemofiltration and hemodialysis (CAVH, CAVHD, respectively) had a marked lowering effect on urea and creatinine serum concentrations. Both artificial liver and renal support contributed to the general clinical improvement and survival of the patient. Further experience in these therapies will be needed to establish better prognosis in such fatal or acute similar conditions.

Treatment of pruritus in cholestatic jaundice by bilirubin- and bile acid-adsorbing resin column plasma perfusion.

The efficacy of plasma perfusion through a new anionic resin, BR-350, for palliation of intractable pruritus secondary to intrahepatic cholestasis was studied in four patients. The treatment was given in a daily 2-h session on 3 consecutive days and was followed by repeated treatment periods each 3rd to 4th week. The patients experienced symptomatic improvement during the first treatment period, and the treatment was well tolerated. Adsorption of bile acids across the filter was efficient and resulted in a bile acid concentration gradient pre- to post-resin of 92%. Thus plasma perfusion through the ion resin BR-350 is an effective and safe treatment for symptomatic relief of intractable pruritus in cholestatic liver disease and may reduce hospitalization time and increase the quality of life.

Experience with vascular access for acute renal failure: using Buselmeier shunt and femoral vessel catheter.

Three types of vascular access were evaluated over a period of 2 years, January 1987-December 1989, in 76 critically ill acute renal failure (ARF) patients. The Buselmeier shunt comprised 75% of the acute vascular access which were utilized, the cannulation of the femoral vessel 23% and the Scribner shunt 2%. The Buselmeier shunt was successfully used alone (mainly in the forearm) in 58 patients for continuous arteriovenous hemofiltration, continuous arteriovenous hemodialysis and intermittent hemofiltration. Thrombosis was noted in 7% of the shunts, where the majority needed a new shunt either on the same or the contralateral arm. Blood leakage was noted in 2%, hematoma in 1%, and accidental bleeding in 1% of the shunts. This study showed that the Buselmeier shunt is more used in our center, most likely because it is easy to bypass the hemodialysis filter by the staff nurse in case of clotting. No major complications were noted even if kept in place for a longer period of time. It offers adequate blood flow for continuous renal replacement therapy and intermittent hemofiltration in ARF.

Plasma atrial natriuretic factor (alpha ANF) during hemodialysis (HD) and hemofiltration (HF).

Plasma concentrations of immunoreactive alpha ANF were measured before, during, and after 3 hours of hemodialysis (HD) and hemofiltration (HF). In seven healthy subjects plasma alpha ANF concentrations were measured to serve as controls. Highly elevated pre-treatment alpha ANF levels were obtained in the HD group (286 +/- 52 pg/ml, mean +/- SE), and in the HF group (275 +/- 48 pg/ml) as compared with the controls (40 +/- 3 pg/ml). The effect of both HD and HF on the alpha ANF concentration was not significant after the first hour of treatment. However, a significant decrease was obtained after the second (HD = 244 +/- 49, HF = 140 +/- 17) and third hours (HD = 244 +/- 48, HF = 135 +/- 15) (p less than 0.05) in both treatments. A steeper decline in the alpha ANF concentration was notable during HF compared with HD. There was a significant difference (p less than 0.05) when both modalities were compared at the end of treatment. A correlation (r2 = 0.98, p less than 0.001) was noted between changes in the alpha ANF levels and the ultrafiltration (UF) volumes only during HF. Plasma alpha ANF concentrations at the filter outlet were lower than at the inlet in both groups. It is concluded that the plasma alpha ANF concentrations are highly elevated in chronic renal failure patients. Despite the decrease in these concentrations during HD and HF it did not reach the normal plasma level. Monitoring of plasma alpha ANF may be a useful indicator for the extracellular volume status during HD and HF treatments.

Pharmacokinetics of intravenous imipenem/cilastatin during intermittent haemofiltration.

The pharmacokinetics of a single iv dose of imipenem/cilastatin (500/500 mg) were studied during and after intermittent haemofiltration (IHF) treatment in six patients with chronic renal failure. The elimination half-lives of imipenem and cilastatin during the IHF treatment were almost identical, 1.4 +/- 0.3 and 1.5 +/- 0.3 h, respectively. Accordingly, approximately 75% of the given dose was eliminated during a 3-h IHF session. However, there was a great difference between the elimination half-lives of the two drugs in the post-treatment period, 3.4 +/- 1.0 and 16 +/- 10 h for imipenem and cilastatin, respectively. The haemofiltration clearance of imipenem was 134 +/- 41 ml/min and that of cilastatin 109 +/- 8 ml/min. On the basis of our results, we suggest that a supplementary dose of imipenem/cilastatin (500/500 mg) should be given directly after the IHF treatment. This dose should be the starting dose for a period of 12-h dosing intervals until the next IHF procedure.

Continuous arteriovenous and intermittent hemofiltration in renal failure.

The clinical applications of continuous arteriovenous and intermittent hemofiltration (CAVH and IHF) have changed the concept of renal failure treatment which was previously understood to be hemodialysis (HD). To perform such treatments a reliable vascular access is a vital priority. Unfortunately, multiple vascular access problems are frequently seen among chronic HD or HF patients despite the reliability of the conventional arteriovenous fistula. In this study a needleless prosthetic vascular access device (Hemasite) has been tried (32 devices in 28 HD/HF patients) as an alternative solution. The five-year follow-up showed that the Hemasite device offered an immediate and reliable vascular access with adequate blood flow. The one-year cumulative survival rate was 55%. Thrombosis and infection were the two main causes for the implant loss. On the other hand, evaluation of our experience with acute vascular access in acute renal failure (ARF) in 76 patients showed that the most commonly used one was the Buselmeier shunt (75%), followed by the femoral catheters (23%) for femoral vessels catheterization, and the Scribner shunt (2%). The Buselmeier shunt gave adequate blood flow. It was safe and easy to manipulate in case of trouble during treatment (e.g. clotting). The outcome of CAVH as a first choice treatment modality for ARF in our centre, since 1982, was evaluated in 40 critically ill intensive care patients during the period July 1987-December 1988. The total survival improved from 45% (in a previous and similar study) to 55%. However, CAVH was found of limited role in uremic control in severe hypercatabolic states. In order to find an alternative solution, CAVH and continuous hemodialysis (CAVHD) were compared in 13 ARF patients. Better results in uremic control were achieved with CAVHD. The net ultrafiltration (UF) volume was lower in CAVHD. Furthermore both UF and diffusion could be combined during CAVHD treatment to give freedom for nutritional support as well as fluid removal. Renal failure patients are prone to infections because they are often critically ill, in case of ARF, or because of their disturbed immune system in case of chronic renal failure. Such patients are in need of urgent and adequate antibiotic treatment. Both renal failure and IHF create difficulties in antibiotics dosing. The pharmacokinetics of a potent broad spectrum antibiotic (imipenem/cilastatin) was studied during IHF for the purpose of dose adjustment. 75% of the given dose was eliminated by HF. Dosage recommendations were given. Fluid overload is a common finding in renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Experience with the Hemasite device in haemodialysis and haemofiltration patients with vascular access problems.

Multiple vascular access failure is a frequent problem and we report our experience with 32 Hemasite devices implanted in 28 patients with end-stage renal disease. All of the patients were on maintenance haemodialysis or haemofiltration with a range of treatment of 1-17 years. Their mean age was 58 +/- 14 years (range 28-72 years). The main indication for using this device as an alternative vascular access was the presence of high-risk patients with a high incidence of previous access failure (1-8 accesses per patient). The majority of the patients were considered as high risk, due either to old age (more than 60 years) (60%) or to the presence of diabetes mellitus (29%). The results of 5 years' experience and follow-up showed that the Hemasite device could be successfully used as a secondary vascular access in high-risk patients who have problems of multiple access failures. The 1-year cumulative survival of the device (55%) was affected by complications such as thrombosis and infection (47% and 16%) which were noted mostly among patients with diabetes mellitus. These complications are the major ones endangering the longevity of the Hemasite implant and were important causes of implant loss (31% and 6% respectively). Being needleless and painless, the Hemasite was well-accepted by the patients and it functioned well, with adequate blood flow. We conclude that the Hemasite device is a valuable alternative when vascular access becomes a problem in haemodialysis patients.