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An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial

THE MAJORITY of the adult human population is seropositive for cytomegalovirus (CMV), a member of the b-herpesvirus family. Normally, infection of immunocompetent individuals does not cause disease. In contrast, infection of immunocompromised individuals, such as patients with AIDS and transplant recipients, can cause severe complications and can even lead to death. Therefore, early detection of active CMV infection is necessary to start effective antiviral treatment. Nucleic Acid Sequence-Based Amplification (NASBA) has been developed for the specific amplification of RNA. In previous studies, we evaluated the diagnostic value of monitoring the expression of the CMV immediate early (IE) 1 and late pp67 mRNA using NASBA, in peripheral blood cells of kidney transplant (Tx) patients. The IE 1 mRNA is expressed directly after entrance of the virus into a cell, while pp67 mRNA is expressed in a late stage in the replication cycle. NASBA results were compared to the techniques that are routinely being used for the detection of CMV: pp65-antigenemia, virus culture, and serology. From this study it was concluded that IE NASBA is a very sensitive assay that detects the onset of CMV infection significantly earlier than the other assays. This is especially valuable for patients that are at risk for symptomatic CMV infection, i.e., seronegative patients with an organ of a seropositive donor and/or intense immunesuppression. The sensitivity and specificity values of pp67 NASBA were comparable to those of the antigenemia assay. We set up a similar study to evaluate the diagnostic value of IE and pp67 NASBA for liver Tx patients. The liver Tx patients are usually severely ill, immunesuppression is more intense compared to the kidney Tx patients and they often have anti-rejection therapy. The results for IE NASBA are presented in this report. The evaluation of pp67 NASBA is still in progress.

Two patients are presented with progressive invalidating uremic peripheral neuropathy. The peripheral neuropathy developed despite frequent hemodialysis with a polyacrylonitril membrane and afterwards in combination with CAPD. The first patient with a long history of progressive peripheral neuropathy before renal transplantation recovered incompletely after renal transplantation, whereas the second patient with a short history of a severe progressive UPN recovered completely after renal transplantation.

Tacrolimus is a very potent drug for preventing all types of acute rejection after renal transplantation. The decrease of vascular rejection may have important long-term implications. This is demonstrated in the 3-year data of the U.S. multicentre trial, where a significant decrease of graft loss was observed in the tacrolimus patients compared to cyclosporine patients. Safety profiles of both drugs are the same, but there are some major differences in side effects. Hyperglycemia is more common during tacrolimus, but generally the induction of hyperglycemia is a dose-dependent reversible process, which leads generally to diabetes mellitus during high systemic exposure, in certain races and prediabetics. Gum hyperplasia and hirsutism are not seen during tacrolimus therapy and there is a more favorable cardiovascular risk profile during tacrolimus as compared to cyclosporine based immunosuppression.

When the effect of HL-A matching on graft prognosis is analysed, the immune status of a recipient of a cadaveric kidney graft, as expressed by the presence or absence of leucocyte antibodies, should be taken into account. Over 300 kidney transplants performed under the auspices of Eurotransplant were analysed in this manner. When the recipient had formed leucocyte antibodies, matching for the antigens of the FOUR series of the HL-A system seemed to be much more effective in improving graft prognosis than matching for the LA antigens: when leucocyte antibodies are absent matching for the HL-A antigens has little effect on graft prognosis, except possibly in the situation when an HL-A full-house identical donor is transplanted. This might indicate that, in the absence of leucocyte antibodies, matching for the mixed-lymphocyte-culture locus is more important than matching for the LA and FOUR loci.

Graft prognosis in 435 leucocytotoxin-free recipients of a kidney graft was not significantly improved by matching for the serologically defined antigens. It could, however, be shown that 108 donor-recipient combinations which shared either the HL-A 1 and 8, or the HL-A 2-12, or the HL-A 3-7 antigens had a significantly better prognosis (70% after 18 months) than 40 combinations mismatched for these antigens (41% after 18 months, p