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Acute renal failure requiring dialysis is a frequent complication in critically ill patients with a high morbidity and mortality. Until recently, no evidence-based guidelines on the optimal treatment modality for renal replacement in the ICU could be issued because of a lack of well-performed randomized controlled trials (RCT). Over the last years however, some important new concepts and RCTs have been published on this topic. An important concept is the understanding that 'chronic dialysis strategies' are not suitable for acute renal failure patients in the ICU. From this understanding the necessity of daily dialysis followed, and later on, the need for flexible treatments related to the patients' need, using slow long extended daily dialysis (SLEDD). Several recent papers compared continuous renal replacement therapy and intermittent hemodialysis (IHD) in ICU patients, pointing to a lack of differences in outcome, but there were less practical problems using IHD, even in unstable patients. In conclusion, it can be stated that all patients can be treated with IHD when available, without jeopardizing their outcome. Slow extended daily dialysis emerged as a hybrid renal replacement therapeutic modality and has promising features because it combines the advantages of both continuous renal replacement therapy and IHD, but until now, no studies evaluating whether SLEDD is superior to 'regular IHD' are available.

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This paper describes and reviews different methods to evaluate the peritoneal transport capacity. This evaluation is important because it will influence the preferred treatment regimen, and will also be a tool for longitudinal follow up both in the individual patient as in patient groups.

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For suitable patients, renal transplantation is still the most preferable renal replacement modality, offering the best outcome in terms of survival and quality of life [Meier-Kriesche, H.U. et al: Semin Dial 2005;18:499-504]. The shorter the period on dialysis, the better the outcome after transplantation seems to be [Meier-Kriesche, H.U. et al: Transplantation 2002;74: 1377-1381]. However, for most patients, a pre-emptive transplantation is not an option by lack of a suitable organ. Therefore, most people have to undergo hemodialysis or peritoneal dialysis (PD) while awaiting a donor kidney. There is evidence that PD positively impacts on the outcome after transplantation [Van Loo, A.A. et al: J Am Soc Nephrol 1998;9:473-481], an effect that could be attributed to a more stable fluid homeostasis, but also to an independent effect of biocompatibility of the dialysis membrane [Van Biesen, W. et al: Transplantation 2000;69:508-514], which is by definition better in PD. Based on these findings, since 1999, all hemodialysis patients at the university of Ghent are dialyzed on a low complement activating dialyzer, and dialysis and especially ultrafiltration in the 24 h preceding the transplantation are avoided as much as possible. A recent re-analysis of the data of the outcome of our transplant program showed that this approach resulted in a reduction of delayed graft function in the hemodialysis patients, allowing to reach an outcome level comparable to that of the PD patients. However, the long-term patient survival still is slightly superior in the PD patients.

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Access to the peritoneal cavity is an essential factor for successful peritoneal dialysis. The technique of catheter insertion can influence technique success and patient satisfaction. As compared to conventional surgical laparotomy, a bedside blind insertion technique under local anaesthesia has logistical advantages for the patient, the hospital and the community. This study compares outcomes of both methods in a single centre. A retrograde analysis of a prospectively collected database on all catheters implanted at the University hospital Ghent between 1/1/1998 and 31/5/2002 was carried out. During this period, catheters were implanted either by conventional laparotomy (CL) or by a bedside blind insertion technique (BI) under local anaesthesia.

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Routinely, maintenance hemodialysis is applied according to an alternate day time schedule with dialysis sessions lasting 3 to 5 h. In analogy with continuous ambulatory peritoneal dialysis, a more gradual and more consistent removal pattern could be achieved by modifying this timeframe, e.g., by applying daily hemodialysis and/or by prolonging hemodialysis sessions to 8 h or more. Recently, a number of dialysis units implemented such alternative timeframes. Both the clinical and metabolic status showed dramatic improvements with beneficial effects on blood pressure, anemia, and potassium and phosphate levels. These changes occurred despite decreases in the dosage of the drugs administered to cope with these problems. However, controlled studies comparing morbidity and mortality of these alternative timeframes to the more traditional approaches are lacking at this moment.

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Patients may complain of pain at the injection site after subcutaneous (s.c.) administration of erythropoietin (EPO). Local pain due to s.c. EPO into the thigh was evaluated in 60 hemodialysis patients in a double-blind, placebo-controlled study. Identical volumes and concentrations (2000 IU in 0.5 ml) of phosphate-buffered epoetin-alpha (EPO-alpha ph), citrate-buffered epoetin-alpha (EPO-alpha ci) and epoetin-beta (EPO-beta) were compared to 0.5 ml of 0.9% saline (SAL), used as placebo. The patients received the 4 injections at the same occasion. For pain evaluation, a verbal scale ranging from no pain (0) to extremely painful (5) and a 10 cm ungraduated visual analogue score (VAS) (0 = no pain, 10 = maximal pain) were used. Treatment acceptance was assessed (yes/no) and expressed as a percentage of the population. Ranking of the preparations from 1 to 4 according to increasing local discomfort was performed. Median verbal pain scores and interquartile ranges were 1.0 (0-2) for SAL, 0.0 (0-2) for EPO-beta, 1.5 (0-3) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 3.0 (2-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). VAS was 0.9 (0.5-2.5) for SAL, 0.9 (0.4-2.4) for EPO-beta, 2.7 (0.8-5.7) for EPO-alpha ph (p < or = 0.001 vs SAL and EPO-beta) and 4.2 (1.7-6.4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). Treatment acceptance was 73% for SAL, 78% for EPO-beta, 60% for EPO-alpha ph (p < or = 0.05 vs EPO-beta) and 32% for EPO-alpha ci (p < or = 0.05 vs EPO-alpha ph). Ranking was 2 (1-3) for SAL, 2 (1-2) for EPO-beta, 3 (1-4) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). In conclusion, s.c. EPO-alpha ph is better accepted than s.c. EPO-alpha ci. However, s.c. EPO-beta is less painful.

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Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in 20 patients, and plasma hirudin levels were followed during this and the 5 following dialyses, without additional hirudin administration. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. Hirudin half-life was > 30 times longer in hemodialysis patients (51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p < 0.001), whereas area under the curve was > 60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml x h, p < 0.001). Distribution volume was lower in hemodialysis patients (11.0 +/- 3.1 vs. 14.1 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.

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The first experience with hirudin as an alternative anticoagulant for heparin in hemodialysis is reported. Recombinant hirudin (HBW 023) was administered in 20 patients as a bolus before dialysis with low flux polysulfone dialyzers (PS400), the dosage being adapted stepwise from patient to patient by 0.02 mg/kg to the occurrence of clotting or bleeding. Four different administration schedules were studied. The first three schedules (0.02 mg/kg, N = 1; 0.04 mg/kg, N = 1; 0.06 mg/kg, N = 4) were discontinued because of clotting. The 0.08 mg/kg schedule was maintained without clotting event in 14 patients. Bleeding was not observed. Plasma hirudin averaged 503.9 +/- 214.0 and 527.7 +/- 217.1 ng/ml after two and four hours of dialysis, and decreased during an interdialytic interval of 44 hours to 223.2 +/- 86.2 ng/ml. Modified antithrombin III (P < 0.05) and activated partial thromboplastin times were lower (P < 0.01) under hirudin compared to heparin; these coagulation parameters were closer to normal during hirudin treatment. The patients developing clotting could be distinguished from those without clotting by the registration of the activated clotting times (9.2 +/- 3.0 vs. 18.7 +/- 3.2 min after 2 hr, P < 0.01; 8.1 +/- 3.0 vs. 16.2 +/- 3.8 min after 4 hr of dialysis, P < 0.05); cut-off value below which clotting is to be expected was 12 min). It is concluded that administration of hirudin as a bolus before the start of dialysis, at a dosage of 0.08 mg/kg, is not complicated by clotting or by bleeding. Coagulation tendency can optimally be monitored by the registration of the activated clotting time.(ABSTRACT TRUNCATED AT 250 WORDS)

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The administration of erythropoietin (EPO) in maintenance hemodialysis may affect urea kinetic parameters by altering dialyzer function during first use and reuse, and dietary protein intake as a consequence of increased appetite. In the present study, the effect of EPO treatment on urea kinetic parameters in case of reuse (n = 14) and first use (n = 10) of dialyzers was assessed in 24 clinically stable hemodialysis patients who were evaluated before and during EPO treatment. In addition, the heparin need and the number of uses before discarding the dialyzer were registered. No significant differences between urea kinetic parameters before compared with during EPO treatment were noted in the overall population or in the subgroups treated with reused or first-use dialyzers. However, in 13 patients with a low baseline protein catabolic rate (pcr(wt)) (pcr(wt) < 1.0 g/kg/24 hr before EPO treatment), pcr(wt) increased from 0.81 +/- 0.04 to 0.93 +/- 0.06 (+ 15%, P < 0.01). The heparin dosage increased from 6,693 +/- 419 IU/session to 7,659 +/- 566 IU/session and from 5,538 +/- 594 IU/session to 6,918 +/- 649 IU/session (P < 0.05) in the subgroups treated with reused or first-use dialyzers, respectively. Nevertheless, when dialyzer reprocessing was performed, the number of achieved uses before discarding the dialyzers was reduced after the introduction of EPO (5.4 +/- 0.4 v 3.4 +/- 0.4, P < 0.01). In conclusion, during EPO treatment urea kinetic parameters were not affected in case of dialyzer first use or in case of reuse. In patients with low pretreatment values, pcr(wt) increased, possibly indicating improved protein intake in malnourished patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cefpirome is eliminated primarily by renal excretion, compelling dosage reduction in kidney failure. We studied the elimination kinetics after intravenous administration of 1 gm cefpirome in patients undergoing hemodialysis (n = 9) and after intravenous (n = 6) or intraperitoneal administration (n = 6) of 1 gm cefpirome in subjects treated by continuous ambulatory peritoneal dialysis (CAPD). Four hours of hemodialysis removed 48% +/- 9% of the drug present in the body at the start of hemodialysis. Consequently, a supplementary dose equal to 50% of the daily dose recommended in end stage renal disease (ESRD) should be administered after each hemodialysis treatment. In patients receiving CAPD, therapeutic levels in both serum and dialysate were reached after intravenous and intraperitoneal administration. The bioavailability after intraperitoneal administration was 84%. After systemic administration, the elimination of cefpirome in the dialysate was negligible. Consequently, systemic dosage of cefpirome in patients receiving CAPD and in patients with ESRD should be identical.

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Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non-complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.

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Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.

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Local pain due to subcutaneous erythropoietin (EPO) injection into the thigh was studied using a verbal score ranging from 0 to 4. Equivoluminous doses of epoetin-alpha (Cilag) and epoetin-beta (Boehringer) were compared in 2 controlled single-blind experiments: 10 dialysis patients were treated at random for 4 weeks at consecutive sessions with both brands of EPO, and 40 patients were treated in 1 session only with the 2 brands simultaneously. Pain scores were 1.12 +/- 0.28 versus 0.15 +/- 0.06 (p less than 0.05) and 1.75 +/- 0.19 versus 0.08 +/- 0.04 for epoetin-alpha and epoetin-beta, respectively (p less than 0.001). Treatment acceptance was 48% for epoetin-alpha versus 83% for epoetin-beta (p less than 0.05).

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