Anticipation of highly sensitised renal patients' immunoadsorption requirements by prescreening using protein A minicolumns.

We are able to subdivide highly sensitised renal patients who wish to enter our immunoadsorption programme into two groups; those who will require acute pretransplant immunoadsorption only and those requiring regular immunoadsorption prior to transplantation. This division of patients is based on the results obtained from laboratory assessment using protein A minicolumns. Patient's plasma is passed down a minicolumn for 6 x 10 min cycles, a sample of plasma is kept after each cycle for analysis by cell flow cytometric cross-match (FCXM). The samples are screened against cells from two normal volunteers, one expressing a previously mismatched Class I HLA antigen (MMA) to which the patient has raised persistent IgG antibodies, the other, whilst not expressing any MMAs, should express a cross-reactive HLA Class I antigen (XRA) to which the patient has formed persistent IgG antibodies. Patients are allocated into the acute pretransplant immunoadsorption group if, after 6 minicolumn cycles, the T cell FCXM vs XRA and MMA is reduced to less than 1 Log median fluorescence intensity shift above the negative control and that both these values have been reduced by at least 15% from the preimmunoadsorption figure. If these criteria are not met, regular immunoadsorption is required under cover of cyclophosphamide. Eleven patients who have been allocated by these criteria have subsequently been transplanted without any incidence of hyperacute rejection.

Evaluation of Doppler ultrasound in primary non-function of renal transplants.

Doppler ultrasound investigation was performed in the renal grafts of 86 patients with primary non-function following cadaveric renal transplantation. Pulsatility Index, defined as: [formula: see text] was assessed to examine its predictive use in the diagnosis of rejection episodes as judged by a retrospective analysis of histological data. Altogether 415 Doppler examinations and 228 renal biopsies were performed. In our population the incidence of rejection was 57%. Using a pulsatility index (PI) > 1.8 to be indicative of rejection, the sensitivity of our test was 68% for vascular rejection and 65% for all rejection episodes. The specificity was 25%. We conclude that Doppler ultrasound cannot replace the need for transplant renal biopsy in patients with primary non-function.

The influence of recipient and donor age on the outcome of renal transplantation.

This paper assesses the impact of age on the outcome of cadaveric renal transplantation. Data are presented on 99 consecutive patients undergoing first renal allografts at one unit. Patients are divided into those aged less than 50 (n = 53), patients between 50 and 60 (n = 16), and those aged 60 years and over (n = 30). There was no significant difference in graft survival at one year between the three groups. There was however an increased mortality with increasing recipient age (1.9%, 12.5% and 20.0% respectively for each age group). The effect of increasing donor age on graft survival was also studied. Graft survival at two years for first grafts was not influenced by donor age. We conclude that age alone is not a criterion for exclusion of patients from transplant programs. In addition we provide data to support the use of elderly donors as a potential source of cadaveric renal grafts for certain patients.

Prevalence of lupus anticoagulant and anticardiolipin antibodies in haemodialysis patients.

It has been suggested that a high prevalence of anticardiolipin antibody and lupus anticoagulant in haemodialysis patients may be a feature of dialysis membrane bioincompatibility. Previously published reports have given a prevalence of approximately 30% for IgG-anticardiolipin and 22-30% for the lupus anticoagulant in a population of haemodialysis patients, with a prevalence of 48% for IgG-anticardiolipin in a subgroup of patients dialysed with cuprophane membranes. The aim of this study was to analyse the prevalence of IgG- and IgM-anticardiolipin antibodies, and also the lupus anticoagulant in a population of haemodialysis patients dialysed exclusively with cuprophane membranes. Forty-two patients on hospital-based haemodialysis were studied. Two patients (4.8%) had IgG-anticardiolipin, and 7 (16.7%) had IgM-anticardiolipin. No patients were positive for both IgG- and IgM-anticardiolipin. All positive results were of 'low' or 'medium' positive titres. In the patients with positive results for anticardiolipin there were no documented episodes of thrombotic events. In the group studied there were no patients positive for the lupus anticoagulant. We conclude that the presence of anticardiolipin antibodies or lupus anticoagulant is rare in this population of haemodialysis patients and they are not a feature of membrane bioincompatibility.

Enalapril can treat the proteinuria of membranous glomerulonephritis without detriment to systemic or renal hemodynamics.

The effect of enalapril on renal hemodynamics and glomerular permselectivity was studied in eight patients with nephrotic syndrome secondary to biopsy-proven membranous glomerulonephritis. The patients received the drug in incremental doses (median, 5 mg) until 24-hour urinary protein excretion had decreased persistently by 30%. Median treatment duration was 6 weeks. Patients were studied three times: (I) after a 4-week run-in period, (II) on the final day of treatment, and (III) after a 4-week wash-out. Median 24-hour urinary protein excretion decreased on treatment from 10.45 g/d to 5.25 g/d and increased to pretreatment levels after the drug was stopped (P less than 0.05 for both changes). Fractional clearance of dextrans greater than 4.1 nm decreased on treatment, indicating both a reduction of macromolecules passing through the shunt pathway of the glomerular basement membrane (GBM) and a possible decrease in ultrafiltration coefficient. There were no significant changes in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), or mean arterial blood pressure (MAP) throughout the study. The effect of enalapril in treating proteinuria appears therefore to be due to a specific intraglomerular action.

Immunoreactive Tamm-Horsfall protein in the kidney and skin of the frog Rana temporaria.

Tamm-Horsfall protein (THP) is the main protein in normal human urine, and is found in the thick limb of the Loop of Henle in human kidney, and in other mammalian species. The skin of the frog. Rana temporaria, has similar physiological properties to this mammalian kidney tissue. In the present study, an immunohistological method involving an antibody to human THP was used to investigate the distribution of this distinctive protein in frog kidney and skin, and to compare its distribution with that found in the kidney tubules of rat and rabbit. THP-positive material was detected in the distal renal tubules and nephric duct of frogs, and was also located in the superficial epidermis of skin. It is suggested that its presence in amphibian skin is consistent with the hypothesis that THP is an important component of tissues that absorb sodium and chloride ions, but remain impermeable to water.

Red cell antigens and renal transplantation.

Donor-specific transfusion was performed with and without cyclosporine between haplomismatched relatives prior to living-donor renal transplantation. Red cell antigen mismatching was not taken as a contraindication to DST. Of 80 patients included in the trial; eleven were ABO-mismatched, 15 were Rh(D)-mismatched, and a further 11 were transfused in the presence of atypical red cell antibodies (anti-D, -C, -Fya, -Kell -N, -H/I -I, -P1, -Wra). Patients were randomized to receive cyclosporine (10 mg/kg) daily during DST or not (control group). The presence of atypical red cell antibodies, with the exception of Rh anti-D, did not appear to influence DST or renal transplantation. DST did not act as a primary stimulus to Rh anti-D production but stimulated preexisting anti D levels. ABO mismatching did not appear to influence DST or subsequent renal transplantation except in one group A [corrected] patient who received group O [corrected] blood and cyclosporine. This patient developed a severe, but self-limiting, autoimmune hemolytic anemia due to auto-anti A antibodies. A similar group A patient in the control group developed an auto-antibody with no clinical sequelae. The influence of cyclosporine on the development of this auto-antibody is uncertain. We conclude that, with the exception of preexisting anti-D antibodies, minor red cell antigen disparities should not preclude pretransplant conditioning with donor-specific transfusions.

Calcium-channel blockers and other factors influencing delayed function in renal allografts.

A retrospective analysis was undertaken to examine the influence of calcium-channel blocking drugs on early renal allograft function. Delayed function was defined as the need for dialysis or a reduction in serum creatinine of less than 15% within 4 days of transplantation. The drug histories of 172 patients were examined. After exclusions, the data from 138 patients were analysed. No patient was taking any calcium-channel blocking drug other than nifedipine. Thirty-one patients were taking nifedipine at the time of transplantation and these had a delayed function rate of 16% compared with 40% for 107 patients not taking nifedipine (chi 2, P less than 0.05). Delayed function occurred in 61% of cases when the donor age was over 50 years compared with 29% with younger donors (chi 2, P less than 0.05). A total ischaemic time of longer than 24 h and administration of inotropic support to the donor were associated with delayed function (chi 2, P less than 0.05). Administration to the donor of mannitol, steroids, phenoxybenzamine and heparin had no effect on the rate of delayed function. Recipients treated with low-dose dopamine in the perioperative period had no advantage. Elevated trough whole blood concentrations of cyclosporin in the first week after transplant were associated with delayed function (Mann-Whitney U, P less than 0.05).

Effect of cyclosporin, previous third-party transfusion, and pregnancy on antibody development after donor-specific transfusion before renal transplantation.

Non-cytotoxic and cytotoxic antibodies were sought after donor-specific transfusion (DST) in 12 potential renal transplant recipients given concomitant cyclosporin therapy and 13 given DST alone. Non-cytotoxic antibodies, which have been shown to develop after third-party transfusion and to be associated with successful transplantation, developed after DST whether or not cyclosporin was given. Donor and panel reactive lymphocytotoxic antibodies developed relatively infrequently after DST with or without cyclosporin. Donor-specific sensitisation occurred only in patients who were multiparous or had over 10 third-party transfusions. Non-cytotoxic Fc-receptor-blocking antibodies may play a part in the improved survival of one-haplotype-mismatched transplants pretreated with DST.

Tetanus: an unusual source and site of infection.

Tetanus is reported in a previously immunised patient who was exposed to the dust of old building plaster containing horse hair. The site of infection was a squamous cell carcinoma of the scalp.