Evaluation of the living kidney donor.

Living donor renal transplantation is the preferred treatment for end-stage renal failure as the risk-benefit ratio for the recipient usually very much favours this approach. However, the benefit for the donor is much harder to define and probably very small if pure medical criteria are considered. Nonetheless 'non-medical' issues (mostly socio-psychological) may outweigh the small medical risk. The medical pre-transplant evaluation of the potential donor must identify absolute contraindications and abnormalities, which would increase the peri-operative risk. Difficulties may arise, if during the process, minor abnormalities are detected that marginally increase the acute or especially the long-term risk or whose implications are not well defined. In this situation two options are available. If the transplant team assumes that donation per se is of no benefit for the donor, transplantation should not be performed. If, however, the supposed 'non-medical' benefit is large enough, this approach will be against the principle of 'doing no harm' because the individual is denied the possibility to help somebody and might suffer from the consequences. In these complicated cases the final decision should be with the potential donor after an intense discussion with everybody involved in the transplantation process. Such an approach, however, necessitates a post-donation follow-up programme to be offered.

Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis membranes via the activation of the complement system.

BACKGROUND: Haemodialysis (HD) with bioincompatible cellulosic membranes like Cuprophan (CU) is considered to influence negatively the clinical outcome of acute and chronic renal failure. In this effect, apart from the disturbance of phagocytosis or oxygen species production by leukocytes, increased apoptosis also has been implicated recently. The objective of this study was to study the effect of HD membranes on apoptosis induction in polymorphonuclear neutrophils (PMN). METHODS: PMN from healthy donors and uraemic patients were isolated and apoptosis was induced by co-incubation with CU, Hemophan or polyamide hollow fibres in the presence of serum from healthy or uraemic humans. Apoptosis was quantified by flow cytometry using Annexin V-FITC and propidium iodide staining and was confirmed by the detection of DNA fragmentation on gel electrophoresis. The deposition of immunoglobulins (Ig) and complement factors on hollow fibres was detected by direct immunofluorescence. RESULTS: Heat inactivation or the depletion of complement components or Ig significantly reduced apoptosis, indicating its dependence on classical complement activation. The detection of IgG on hollow CU fibres and the restored acceleration of apoptosis by the appropriate replenishment of Ig-deficient sera additionally confirmed these findings. Inhibition experiments revealed that caspases were necessary mainly, but not exclusively, for apoptosis to occur after complement activation. Uraemia led to increased PMN apoptosis in the presence of bioincompatible, but not biocompatible, membranes. CONCLUSIONS: Our results suggest that the acceleration of PMN apoptosis in the presence of CU is mediated via an antibody-dependent activation of the classical complement pathway mobilizing both caspase-dependent and -independent pathways.

Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up biopsies: a report of three cases.

Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsy-proven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d.