ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The monoclonal antibody, Orthoclone OKT3 (OKT3), has been used with great efficacy in a prospective multicenter trial as therapy for first rejection episodes in cadaveric donor (CD) renal allograft recipients treated with azathioprine (AZA) and prednisone (P). However, although almost all rejection episodes were reversed, recurrent rejection occurred in approximately two-thirds of OKT3-treated patients in this earlier trial; infections also occurred in about two-thirds of patients, often related to the additional immunosuppression necessary to reverse the rerejection episodes. In the current series of patients, OKT3 was used to treat rejection in CD renal graft recipients in a protocol differing from the multicenter trial in two respects: (1) baseline immunosuppression was cyclosporine (CsA) and P or CsA, AZA, and P (probably more potent immunosuppressive combinations than the AZA and P in the multicenter trial); and (2) OKT3 treatment was reserved for rejection episodes resistant to 3 bolus infusions of methyl-prednisolone (MP), 5–10 mg/kg, rather than as primary therapy for first rejection episodes. Using this protocol, 46 of 74 rejection episodes (62%) diagnosed between 3/85 and 3/86 in CD renal allograft recipients were treated successfully with MP. Of the remaining 28 steroid-resistant rejection episodes, 27 (96%) were reversed with a 7–14-day course of OKT3, 5 mg/day. Only 5 recurrent rejection episodes (19%) have been observed in the 2–14-month follow-up period after OKT3 treatment; infections have occurred in 10 patients (36%), and three grafts (11%) have been lost in OKT3 treated patients. These results suggest that recurrent rejection and subsequent infection after OKT3 is used to treat rejection may be reduced in a protocol where CD renal allograft recipients are treated with baseline immunosuppression regimens including CsA and where OKT3 is reserved for steroid-resistant rejection. This approach appears to be both more cost-effective than, and as effective therapeutically as, treating all first rejection episodes with the monoclonal antibody.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The factors responsible for B cell regulation in stable renal transplant patients are unknown. To examine these control mechanisms, the B cell responses to 4 mitogens (pokeweed, wheat germ agglutinin, lipopolysaccharide, and SAC-1), which are known to stimulate B cells by different mechanisms, were measured in two groups of stable long-term (greater than 1 year post-transplant) renal transplant recipients. The first group were patients who had been transplanted under conditions of a negative crossmatch on all available pretransplant sera (negative crossmatch group) and the second group were patients who might have a unique regulation of B cell function in that they had been successfully transplanted under the conditions of a negative crossmatch using sera at the time of transplant but with pretransplant sera that gave a positive donor-specific T cell crossmatch (positive crossmatch group). Stable transplant patients were found to have significantly impaired responses to all four mitogens tested. Furthermore there were no differences in the responses of the negative crossmatch patients as compared with the positive crossmatch patients. The lack of response to mitogens was not due to a lack of proliferation of cells or to a loss of viability in culture. The number of cells in culture was the same in negative crossmatch patients and controls but was significantly less than controls in positive crossmatch patients (P

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We retrospectively reviewed the clinical data of all renal transplant patients treated with cyclosporine as their main chronic immunosuppressive agent between 12/83 and 11/85 to identify cytomegalovirus-negative patients at our institutions who received cytomegalovirus (CMV)-positive kidneys. Using a latex agglutination test, twenty-two such patients were identified, of whom 2 were excluded due to early death and lack of posttransplant follow-up serology. Of the remaining 20 patients, 12 developed CMV antibody in the first 4 months post-transplant, and of these, 11 were hospitalized with complications related to primary CMV disease. Two of these seroconverting patients eventually died, and one lost her kidney. Of the 8 persistantly CMV-negative patients, 1 lost his kidney soon after transplantation, and one had a febrile illness 4 months posttransplant caused by a bacterial pneumonia. Concomitantly, 145 renal transplants (CMV-negative recipient receiving a CMV-negative kidney or CMV-positive recipient receiving either positive or negative kidneys) given to 142 patients functioned for at least 4 weeks. Only 3 cases of CMV reactivation disease occurred in previously antibody-positive patients. We conclude that the transplantation of a cytomegalovirus-positive kidney into a CMV-negative recipient carries a high risk of mortality/morbidity from primary cytomegalovirus disease. On the other hand, reactivation of CMV disease was uncommon early in the posttransplant course of cyclosporine-treated patients.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To assess the impact of diabetes on vascular complications occurring in renal transplant recipients, we compared the incidence of vascular disease in 283 non-diabetic (ND) and 99 diabetic (D) patients who received primary cadaver renal transplants at our center between 1/1/76 and 12/31/85. The median observation time in the ND patients was 31 months, and in D patients it was 20 months. Both ND and D patients were subdivided into group A if they had preexisting clinical vascular disease and group B if they had no prior disease. The vascular complications between the ND and D patients were analyzed in 3 subsets: prevalence of vascular disease prior to renal transplantation; posttransplant recurrent vascular disease in group A; and posttransplant vascular disease, new, in group B.The results showed that, prior to renal transplantation, D patients have a higher prevalence of clinical vascular disease (33%), compared with ND patients (13%) (P= .00001). In group A, the recurrence rate of vascular disease after transplantation was also higher in D patients (67%) compared with ND patients (40%) (P= .05). In group B, the incidence of posttransplant vascular disease (new) was significantly higher in D patients (33%) compared with the ND patients (13%) (P= .002). Also, the amputation rate was significantly higher in D patients (18%) compared with ND patients (0.4%) (P= .000001).Our data suggest that morbidity from vascular disease is significantly increased in diabetic renal transplant recipients compared with nondiabetic patients. Such increased morbidity from vascular disease in the diabetic patients may also be observed in the period before renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8—1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150–200 ng/ml during the first month, 100–150 ng/ml during the second month, 75—100 ng/ml during the third month, and 50—75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7±3.1 mg/kg at 6 months, 5.5±3.2 mg/kg at 12 months, and 4.7±2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94±59 ng/ml, 64±22 ng/ml, and 44±21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8±0.6 mg/dl at 6 months, 1.7±0.5 mg/dl at 12 months, and 1.6±0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6±0.5 vs. 1.4±0.4 mg/dl,P=.31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50—75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID