SummaryRecently, 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 (HDj) 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 HDj, 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 ± 2.0 1, 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.

PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.

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It is concluded that rHuEpo during the first weeks after RTP is of benefit in the correction of the Hct in the early post-surgical period, in spite of relative Epo resistance.

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No changes in rHuEpo dose were observed after conversion from s.c. to i.v. There were no significant differences between the conversion and non-conversion group. These results are in contrast to some earlier studies suggesting lower rHuEpo requirements in case of s.c. administration.

It is generally accepted that Fabry disease (angiokeratoma corporis diffusum) is an X-linked disorder resulting from the deficient activity of the lysosomal enzyme α-galactosidase. In males, the enzymatic defect leads to accumulation of glycosphingolipids, particularly in the kidney which causes end-stage renal disease. We report here a woman who presented in 1987 with focal and segmental glomerulosclerosis and required hemodialysis 4 years later when her son was evaluated for proteinuria. In these patients morphologic, biochemical, and genetic investigations were performed to explore the possibility of a hereditary renal disorder. Ultrastructural examination of the son’s renal biopsy specimen revealed lamellated osmiophilic inclusions in the glomeruli, typical of Fabry disease. Four months after kidney transplantation in the mother, a graft biopsy specimen also revealed dense lamellated inclusions on electron microscopy. The leukocyte α-galactosidase activity was 0.008 µmol/min·10⁹ cells in the son and 0.070 in the mother (range 0.100-0.500 µmol/min·10⁹ cells). The diagnosis of Fabry disease was confirmed in both patients by the identification by DNA sequencing of a novel mutation in the α-galactosidase gene: one single base pair deletion in exon 3 (7317delA). In conclusion: (1) end-stage renal disease may occur in heterozygous women with Fabry disease; (2) morphologic lesions due to glycosphingolipid accumulation may be observed in the renal allograft after transplantation, and (3) DNA analysis confirmed the diagnosis by demonstrating a frameshift mutation, which has as yet not been reported.