G. Proud

Urological complications following renal transplantation

A total of 1016 consecutive renal transplants performed between 1976 and 1990 were analysed retrospectively to determine the incidence of urological complìcations and possible predisposing factors. Some 189 episodes of ureteric obstruction and/or urinary leak occurred in 143 patients (overall incidence 14.1 %). The median annual rate of urinary leak was 5.1%; that of ureteric obstruction was 4.5% pre-1986 and 16.1% post-1986. Sixty-three episodes of urinary leak occurred in 54 patients from 1 day to 3 months post-transplant and 60% involved the distal ureter. Thirty were treated primarily by reconstructive surgery, ten required nephrectomy and three died of associated sepsis. A total of 126 episodes of ureteric obstruction occurred in 104 patients from 1 day to 12 years post-transplant and 86% involved the distal ureter. Prior to 1986, 10/11 patients with ureteric obstruction were treated by reconstructive surgery, but since then 88 (95%) have been treated by percutaneous nephrostomy, with or without stenting, with only one graft lost and no deaths. Children had a significantly increased incidence of ureteric obstruction (P<0.001) whilst male recipients had an increased incidence of urinary leak (P=0.04). More patients with ureteric obstruction than those without had two or more episodes of rejection (P=0.03). No single cause for the increased incidence of ureteric obstruction since 1986 has been identified. Continued attention to technical detail and further study of this trend is warranted.

The value of posttransplant monitoring of interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23 in the plasma of renal allograft recipients.

Over the past few years, the central role of cytokines in the amplification of the immune response has been reported and several studies have examined the relationship between the plasma level of individual lymphokines during renal allograft rejection. The aim of the present investigation was to study simultaneously IL-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23. Analysis of results has allowed both the prognostic value and any possible interrelationships between the measured cytokines to be determined. We studied 16 renal transplant recipients for the first 14 days after transplantation. Seven patients showed clinical evidence of acute allograft rejection and 5 showed excellent stable graft function with no signs of rejection. Primary nonfunction was seen in 4.

Administration of ATG according to the absolute T lymphocyte count during therapy for steroid-resistant rejection

Abstract. In renal transplantation, treatment of steroid‐resistant rejection (SRR) with antithymocyte globulin (ATG) has been widely reported but over‐immunosup‐pression remains a common problem. In the first ten patients (group 1) treated for SRR with rabbit ATG, three developed serious viral infections and two deaths occurred due to CMV pneumonitis. ATG was only omitted if thrombocytopenia or neutropenia occurred. In the next 17 patients (group 2) with SRR, ATG was administered according to the absolute T lymphocyte count. T lymphocytes were measured by flow cytometric analysis of CD3‐labelled lymphocytes. ATG dosage was adjusted on a daily basis to keep the absolute T lymphocyte count under 50 cells/μl. Administration of ATG according to the absolute T lymphocyte count resulted in a significant reduction in the mean dose of ATG given to the group 2 patients (P < 0·001). A significant decrease in the incidence of serious viral infections (P= 0·04) was achieved without reducing the ability of ATG to reverse the SRR (P= 0·29) or increasing the number of grafts lost at 1 year in the group 2 patients (P= 0·23).

Flow cytometric crossmatching in renal transplantation—the long-term outcome

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now no long-term follow-up on such patients has been available. In this study, 117 renal transplant patients were followed up for a period of 5 years. Of these 21 were known to have donor T cell directed IgG and five had B lymphocyte directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (p < 0.0001, Handel Maenzel test). Patients with antibody detected preoperatively were tested again either at the time of graft failure or at 5 years post-transplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts the levels increased in 60% of cases, but those who retained their grafts also had an increase in levels of donor directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However when IgG isotypes were considered, in those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (not significant).

Flow cytometric crossmatching in renal transplantation ‐ outcome after five years

Abstract  The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor out come is well described in renal transplantation. Until now, no long‐term follow‐up on such patients has been available. A total of 117 renal transplant patients were followed up for a period of 5 years. Of these, 21 were known to have donor T cell‐directed IgG and 5 had B lympho cyte‐directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (P < 0.0001 Han del Maenzel test). Patients with antibody detected preoperatively were tested again, either at the time of graft failure or at 5 years posttrans plantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts, the levels increased in 60 % of cases but those that retained their grafts also had an increase in levels of do nor‐directed antibody in 50 % of cases. The changing levels of anti body therefore appeared to have little relevance to outcome. However, when IgG isotypes were considered, for those who experienced graft failure and also had a γ3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with γ3 had a decline in levels between preoperative and 5–year sam ples in three of the four cases (p not significant).

Developing the ideal immunosuppressive protocol by internal audit.

To identify the best immunosuppressive protocol in a centre where five different regimens are employed, 227 consecutive renal recipients who were transplanted over a 2.5-year period were studied. The five different regimens employed were cyclosporin monotherapy, dual therapy (cyclosporin and prednisolone), triple therapy (cyclosporin, azathioprine, prednisolone), antithymocyte globulin (ATG) followed by dual therapy and ATG followed by triple therapy. Recipients were chosen for the different regimens according to HLA mismatch, positive donor crossmatch due to IgM, regraft and delayed graft function. The group with the lowest risk, cyclosporin monotherapy, had the highest acute rejection rate, with only 13% free of acute rejection (in comparison to triple immunosuppression, P=0.024, chi-square test). The overall infection rate and graft success rate were similar between the different groups.

Renal epithelium: reversal of cytotoxic damage by addition of anti-thymocyte globulin

Abstract. A novel in vitro assay of renal epithelium tight junction function was used to assess the efficacy with which rabbit anti‐thymocyte globulin (ATG) blocks epithelium damage mediated by lymphokine‐activated killer (LAK) cells. It was found that LAK cells lysed renal epithelial cells poorly in standard chromium‐release assays but that they caused a rapid, and almost total, reduction in trans‐epithelium monolayer resistance, indicating tight junction failure and, hence, loss of tissue function. LAK cell‐mediated cytolysis of the sensitive K562 cell line was completely blocked in the presence of ATG at a concentration of 200 μg/ml. Addition of ATG at this concentration to damaged renal cell monolayers in the presence of LAK cells allowed the trans‐monolayer resistance to recover rapidly to levels approaching the values recorded before initial addition of LAK cells. On this basis it seems likely that the rapid restoration of renal function frequently observed after appropriate “rescue” therapy during episodes of acute rejection may reflect subtle changes in tissue function rather than recovery from widespread graft cell cytolysis.