The use of human gamma globulin in renal transplantation.
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Biomedical subjects
Publications and source records attributed to R R Riggio.
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The total number of cadaveric kidney transplants has been declining, despite an increasing dialysis population, greater understanding of transplant immunology, and improved transplant management. To explore the causes of this decline, various factors were studied in 140 dialysis patients who were awaiting transplantation and 100 consecutive recipients of cadaveric kidney transplants. The study indicates that there is a growing, now predominant, prospective kidney recipient population that is highly sensitized because of previous blood transfusions and kidney transplantations. As a result, 92% of the prospective recipients exhibit varying degrees of lymphocytotoxic antibodies. Thus, a major problem in clinical transplantation is the growing number of dialysis patients who are virtually untransplantable. The declining number of cadaveric kidney transplantations may be caused by, in part, changing immunologic characteristics in the recipient population.
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We analyzed clinical and pathologic data from 36 recipients of 38 renal allografts who developed nephrotic syndrome following transplantation. Three groups were identified on the basis of histologic changes in the graft, and each group had a distinct clinical course. Nine grafts (23.7%) had recurrent glomerulonephritis (GN) (5 membrano-proliferative, 4 focal glomerulosclerosis) and developed nephrotic syndrome at 5.1 months (mean) posttransplant. Renal function deteriorated rapidly, with a 2-year graft survival of 29.7%. Four grafts (10.5%) with de novo GN (3 epimembranous, 1 minimal change) developed nephrotic syndrome at 32 months posttransplant, and all functioned for more than 3 years. Twenty-five grafts (65.8%) had allograft glomerulopathy with the onset of nephrotic syndrome at 9.1 months posttransplant and a 2-year graft survival of 66.6%. The differences in duratin of graft function between grafts with allograft glomerulopathy and recurrent GN (P < 0.01) and in graft survival rates at 2 years among the three groups (P < 0.05) are statistically significant. This analysis indicates that allograft glomerulopathy is the most common cause of kidney transplant nephrotic syndrome. Membranoproliferative GN and focal glomerulosclerosis may recur soon after transplantation and rapidly progress to renal failure in marked contrast to grafts with either de novo epimembranous nephropathy or minimal glomerular change, lesions that are compatible with prolonged graft function.
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We observed an epidemic of parainfluenza type 3 viral infection in a renal transplantation service among 16 recent transplant recipients. To assess the effect of infection on transplant function, we retrospectively compared the infected patients with a matched, uninfected control group. In addition to symptoms of a mild upper respiratory tract infection associated with the epidemic, there was an increase in the frequency of acute rejection episodes during the period of infection in the infected group. Nevertheless, outcome in terms of patient and graft survival at six months was not affected when compared with the survival rates of the control group.
Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.
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Ninety seven transplant recipients participated in a controlled, clinical trial measuring the graft-enhancing property of a human gamma globulin preparation. The latter was prepared from the blood of pregnant women (RPGG) and contained antibodies with specificities for HLA locus products. Data analysis indicated that RPGG treated recipients had enhanced survival rates of their grafts if they had received one or more blood transfusions prior to transplantation.
The effect on cadaver-kidney transplant survival-rates of a gamma-globulin concentrate, prepared from clotted blood centrifugally expressed from placental tissue recovered from postpartum women, was evaluated in a prospective controlled trial in 195 patients who were also given a standard immunosuppressive regimen. Allograft-survival rates were analysed according to whether or not the recipient had lymphocytotoxic antibodies before transplantation (responders) and whether the graft was a first or second transplant. The graft-survival rate was improved in responder-type recipients of first transplants who had received the gamma-globulin concentrate as adjunctive therapy (control group 28.8+/-10.1% vs. gamma-globulin 55.5 + 9.7% at 2 years, p less than 0.05). The survival-rate of grafts in non-responders was not affected by administration of gamma-globulin and data on its use in recipients of a second graft were insufficient for analysis. These results suggest that the gamma-globulin concentrate was suppressing immunological responses associated with humoral-type rejection.
We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.
Experience with renal allograft fracture occurring in 21 of 246 transplants performed over a 29-month period is reviewed. Clinical manifestations included pain and tenderness at the graft site, fever, and falling hematocrit. The fracture occurred without exception in the course of an acute rejection episode. Diagnosis was made from two days to seven weeks following transplantation; in 13 patients (62%) diagnosis was made within two weeks of surgery. Severe damage to the kidney necessitated nephrectomy in all but two transplants. Of those not removed at initial exploration only one regained function to permit a dialysis-free existance for several months. Histologic examination of the fractured kidneys revealed the pathogenesis to be acute rejection in 13 (62%), accelerated acute rejection in four (19%), and a combination of these processes in four (19%). Conclusions from this study are that fractures of renal allografts: (1) are more frequent than commonly realized; (2) are primarily due to the swelling of acute rejection; (3) are often characterized by sudden onset of pain in the region of the graft accompanied by fever and falling hematocrit; (4) should be treated by prompt surgical intervention to control hemorrhage, to perform nephrectomy if indicated, and to evacuate the hematoma in order to reduce the possibility of secondary infection.
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The effects of removal of all renal tissue on hematopoiesis, osteodystrophy, blood pressure regulation and metabolic functions are reviewed; and, the indications for, and results of, bilateral nephrectomy are discussed. Nephrectomy results in a more severe anemia in dialysis patients which is poorly responsive to androgen therapy. No differences were detected in the severity of osteodystrophy between nephric and anephric patients. However, bilateral nephrectomy can occasionally result in the acute onset of hypocalcemia. Blood pressure regulation must be accomplished in the absence of a functioning renin-angiotensin system. This is largely on the basis of volume, but changes in vascular tone may also be significant. Little is known about the metabolic consequences of nephrectomies. The effect on substances metabolized by the kidney is an area for further investigation. Kidney tissue should be preserved, if at all possible, and nephrectomy performed only for specific indications.
A case of renal transplantation between HL-A identical siblings is reported in which the donor kidney was found to have a calcified mass in the upper pole. Because an immediate pathologic diagnosis could not be made at the time of nephrectomy, the kidney was preserved with pulsatile perfusion for fifty-four hours after excision of the upper pole. At that time the diagnosis was still not available, and transplantation was performed only to have the report of ossified renal cell carcinoma established the following day.