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Deaths from Occlusive Arterial Disease in Renal Allograft Recipients

In a series of 325 recipients of cadaveric renal transplants sudden occlusive arterial disease was found to be responsible for 12% of deaths. Acute myocardial infarction (9%) occurred 25 times more than expected in the normal population and cerebral thrombosis (3%) 300 times more. The greatest loss was in the initial three-month period after transplantation. Patients with renal failure due to essential hypertension were especially at risk, accounting for six of the 12 deaths.

Immunoglobulin abnormalities in renal transplant recipients

Five renal transplant recipients were observed to have recurrent infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 polyclonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.

Identification of the cellular subpopulations infiltrating rejecting cadaver renal allografts: Preponderance of the T4 subset of T cells

In the rejection response against renal allografts, the relative importance of helper/inducer T cells mediating a delayed-type hypersensitivity response and of T cells with direct cytotoxicity has not been defined. These subpopulations were identified with commercially available monoclonal antibodies and an indirect immunoperoxidase technique in 31 renal biopsies from patients undergoing acute rejection episodes and in 9 rejected nephrectomy specimens. T lymphocytes were the predominant cell population in all biopsies and in 8 of 9 nephrectomies. The T4 helper/inducer subset was equal to, or greater than, the T8 cytotoxic/suppressor subset in 28 of the 31 biopsies and in the 8 nephrectomy specimens that had histological evidence of cellular rejection. T4 lymphocytes were found predominantly in large areas of cellular infiltrate. T8 lymphocytes had a more diffuse interstitial distribution and were a minority of the cells in the large areas of cellular infiltration. These results show that helper/inducer T lymphocytes are often more frequent than cytotoxic/suppressor cells in acute renal allograft rejection in humans and they suggest that helper/inducer T cells may play an important role in the mediation of graft destruction.

REVERSAL OF RENAL FAILURE BY REVASCULARISATION OF KIDNEYS WITH THROMBOSED RENAL ARTERIES

Abstract The case-reports of three patients with hypertension and sudden deterioration of renal function are presented. Two patients were uraemic, one requiring dialysis. Angiography revealed renal arterial occlusions unilaterally in two patients and bilaterally in one. In all three patients renal biopsy performed at operation revealed ischaemic but viable kidneys with occluded arteries. Revascularisation resulted in reversal of renal failure and restoration of good health.

COMMUNITY TREATMENT OF END-STAGE RENAL FAILURE BY DIALYSIS AND RENAL TRANSPLANTATION FROM CADAVER DONORS

Abstract A collaborative project involving twenty hospitals and a central tissue-typing service has allowed the treatment by dialysis and transplantation from cadaver donors of all suitable patients who have presented with irreversible renal failure. The rate of presentation of patients was between 45 and 50 per 1,000,000 of population per year. For transplantation all hospitals cooperated in access to donor organs. Potential recipients maintained by repeated dialysis in six of the hospitals formed a common recipient pool. Both donor kidneys were used whenever possible, and one was transplanted to each of the 2 most compatible recipients as determined by tissue-typing. Operations were performed simultaneously in two of the hospitals, and administrative arrangements allowed the free movement of transplantation personnel between hospitals. In two years since August, 1967, 190 patients with end-stage renal failure presented. 175 were treated by dialysis, all but 14 by haemodialysis; 90 patients subsequently received renal allografts, 55 await operation, 7 have permanent dialysis, and 29 died of complications of renal failure or of dialysis. Of those who underwent operation 68 remain alive, 62 with functioning allografts. 34 patients (71%), including 3 with secondary grafts, have allografts which have functioned for more than a year since transplantation. Although tissue-typing was consistently completed before operation and resulted in improved compatibility, few patients were well matched. It is concluded that hospital collaboration will allow the treatment of all young and middle-aged patients with irreversible renal failure, and that the incidence of end-stage renal failure is at present at least 45-50 per 1,000,000 of population per year in Australia. This incidence can be reduced,

Long-term survival after cadaveric renal transplantation.

In a series of 404 consecutive first cadaver kidney transplants performed since 1967 the actuarial five- and 10-year survival of patients were 61% and 47% respectively and of grafts 46% and 36%. In more than four-fifths of the patients surviving these intervals the original cadaveric grafts were functioning at these times, and most of the remainder were sustained by subsequent grafts. Although graft survival has remained static since 1967, patient survival improved. Results for 43 consecutive second cadaver transplants were similar after five years to those of first grafts. These results promote the acceptability of cadaveric transplantation as a long-term treatment for chronic renal failure.

Tissue matching and early rejection of cadaveric-donor renal allografts: the importance of unidentified donor antigens.

Tissue typing has been reviewed in a series of 100 technically successful cadaveric-donor kidney grafts. The criterion of transplant failure was immunological rejection causing total loss of function within three months of operation. No significant correlation was observed between matching grade and graft failure due to early acute rejection. This is attributed to the failure to detect at least one “LA” or “4” antigen (as defined in our laboratory), representing a potential incompatibility, in 89% of the grafts, and in the remaining 11% to the lack of an available recipient with identical “LA” and “4” typing. Undetected antigens on the donor are usually incompatible, and probably these incompatibilities unfavourably influence early graft survival. If the results of cadaveric-donor renal transplantation are to equal those of transplantation from well-matched living related donors it will be necessary to type with sera which can recognize individually all HL-A antigens, including those not yet identified, and to create an international pool of over 1,000 potential recipients.

Diagnosis of Renal Allograft Rejection by Analysis of Fine-Needle Aspiration Biopsy Specimens With Im-munostains and Simple Cytology

Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified—heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function.

Immunopathology of Renal Allograft Rejection Analyzed With Monoclonal Antibodies to Mononuclear Cell Markers

The composition of the mononuclear cell infiltrate in rejecting renal allografts was determined on 96 renal biopsies and 22 nephrectomy specimens by the use of monoclonal antibodies to mononuclear cell surface markers and an indirect immunoperoxidase staining technique. During rejection the composition of the infiltrate was heterogeneous, with T cells (T11), monocytes (OKM1) and HLA-DR expressing mononuclear cells the most frequent sub-populations. B cells (B1) and activated T cells, identified by OKT10, were always in the minority. The T cells infiltrate usually included the helper/inducer (T4) and cytotoxic (T8) subclasses, which suggests that both may contribute to the mediation of rejection. Whether T4 or T8 predominated in the graft did not relate to the ratio of T4:T8 in blood, the HLA A, B or DR incompatibilities of the graft, or the immunosuppressive used. The frequency of T11, T4, T8, HLA-DR positive cells and monocytes, but not B cells, increased with the severity of rejection and was similar in biopsies from patients immunosuppressed with Cyclosporine (CSA) to those given a combination of azathioprine, prednisone and antilymphocyte globulin (AZA). Severe rejection episodes which did not respond to treatment with corticosteroids were more often characterized by a predominance of T8 over T4 cells and T cells infiltrating the glomeruli. In grafts with evidence of cellular rejection, renal tubular cells were shown to have a marked increase in their expression of HLA-DR antigens compared to normal kidneys or grafts with minimal rejection. The expression of HLA-DR antigens on graft tubular cells correlated with the presence of T cells in the interstitium and the severity of rejection, except for moderate rejection in CSA treated biopsies, in which HLA-DR expression was lower than in AZA biopsies. These immunopathological studies have demonstrated that a variety of potential effector cells exist within the graft, and several features have been identified which may assist in assessing the prognosis of the rejection episode.

Long-Term Survival after Cadaveric Renal Transplantation

In a series of 404 consecutive first cadaver kidney transplants performed since 1967 the actuarial five- and 10-year survival of patients were 61% and 47% respectively and of grafts 46% and 36%. In more than four-fifths of the patients surviving these intervals the original cadaveric grafts were functioning at these times, and most of the remainder were sustained by subsequent grafts. Although graft survival has remained static since 1967, patient survival improved. Results for 43 consecutive second cadaver transplants were similar after five years to those of first grafts. These results promote the acceptability of cadaveric transplantation as a long-term treatment for chronic renal failure.