摘要:

In cylosporine (CsA)-treated renal transplant recipients complete corticosteriod withdrawl followed by CsA monotherpy has been associted with severe rejection episodes in a significance proportion of patients. We report the results of replacements of steroids by azathioprine (AZA) in 25 primary cadaveric renal transplant recipients initially treated with CsA and methylprednisolone (MP). MP taper was started 8.85.6 months posttrasplant when the MP dose was either 10mg/day or 20 mg every other day. MP was tapered off over a 5-month period. At the initation of MP taper, AZA was added at 1 mg/kg/day and increased to 1.5 mg/kg/day after two months. The CsA dose was adjusted to maintain trough serum levels as measured by radioimmunoasay (RIA) of 50–75 ng/ml, during and after MP with drawl. Seventeen patients have remained continuously off MP for 14.65.0 months with stable renal function. Reinstitution of MP at 10 mg/day was required in 8 patients, 6 for rejection (1.80.7 months after MP with drawl), 1 for AZA-indiced leukopenia, and 1 for denovo glomerulopathy. Renal function returned to baseline in all 6 patients have again been successfully retapered off MP. In the patients withdrawn from MP, body weight and mean arterial blood pressure had decreased by 2.11.3 kg (P<.05) and 117 mmHg (P<.05), respectively, at the time of the most recent follow-up compared with values at the initiation of steroid withdrawal. The number of blood pressure medications per patient decresed by 38% (P<.05) and 6 patients were able to discontinue all antihyupertansive drugs after cessation of steroids. Discontinuation of MP also resulted in a decrease in serum cholesteorl concentration from 24850 to 21755 mg/dl (P<.05). We conclude that steroids can be replaced by AZA in the majority of CsA-treated primary cadaveric renal transplant recipients by the end of the first posttransplant year withour an adverse effect on graft survival. This protocol resulted in significant reductions in serum cholesterol, mean arterial blood pressure, and body weight, and may avoid the long-term siode effects of steroid therapy.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Intavenous digital subtraction renal angiography (IV-DSRA) is frequently used in the preooperative evaluation of living-related (LR) kindney donors. However, the true accuracy of IV-DSRA in th donor population is difficult to assess since abnormalities of the kidney and its circulation are uncomon in this group. Therefore, we evaluated IV-DSRA in a group of patients more likely to have anomalies and abnormalities that would affect LR donor selction, donor nephrectomy, and subsequent transplantation. Hypertensive adults being evaluated for renovascular hypertension had IV-DSRA and conventional renal arteriograms, which were interpreted indepenmdently. We determinded the accuracy of IV-DSRA, compared with conventional arteriography, in detecting multiple renal arteries,l renal artery stenosis, fibromuscular dysplasia, and abnormal renal parentchyma. Technically unsatisfactory studies were excluded from analysis.Of 59 patients evaluted, 37 had abnormalities or anomalies. IV-DSRA failed to detect 28 of 50 findings in these 37 patients. In 21 patients with multiple renal arteries, IV-DSRA underestimated the number of main renal artery stenosis, present in 16 patients, was undetected by IV-DSRA in 3 of these patients. Mild fibromuscular dysplasia was not detected by IV-DSRA in any of the 5 patients with this condition, and abonormalties of renal parenchyma were not detected in 6 of the 8 patients with scarred or cystic kidneys.When compared with conventional renal arteriography in a hypertensive population, the IV-DSRA does not accurately detect abormalities of the kidney and its circulation. It these data are confirmed in nonhypertensivse subjects, preopertive evaluation of LR kindney donors using IV-DSRA alone may fail to detect potentially important anatomic abormalities.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In order to determine whether th protenuria observed in some renal donors was glomerular or tubular in orgin, and to determine whether creatinine clearanee was an accurate index of glomerular filteration rate (GFR) in subjects with reduced nephron mass, 29 donors were evaluated 9–18 years after uninephrectomy. Results were compared with those in 31 age-, sex-, and race-matched controls evaluated at the same time. Mean creatinine clearacne (Ccreat) in donor was 78% that of controls, which was similar to the 85% ratio of inulin clearance (Cin) in donors compared with that of controls. Furthermore, the ratio of Ccreat/Cinwas similar in both donors adn controls. One third of the renal donors had an elevated albumin excreation compared with controls (microalbuminuraia [12–220 mg/24 hr] in seven patients; 301 and 1084 mg/24 hr in two patients). There was no correlation between albuminuria an blood pressure, nor was there a demonstrable clinical cause for the albuminuria in most patients. In contrast to these recults, excreation of beta-2 microgluobulin, an index of tubular proteinuria, was normal in all but one patient. The prevalence of hypertension was higher in donors compared with the expected prevalence adjusted for age, sex, and race.These reuslts verify that creatinine clearance is a reliable measure of GFR in long-term renal donors. They also demonstrate an increased frequency of glomerular proteinuria and hypertension in renal donors. Despite these mild abnormalties, GFR is well preserved for up to 18 years postuninephrectomy.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Since February 1986, 23 patients have received Orthoclone OKT3 treatment at our transplant center for renal allograft rejection resistant to steroids and antilymphocyte globulin (ALG). They have been followed for at least 4 months as of this study time (range: 4–15 months). We report here our experience with OKT3, including five late responders—as late as 116 days after OKT3 treatment.Overall rejection was reversed in 19/23 (83%). Rejection was controlled in 95% of primary an 50% of non primary transplants; 89% of the male and 80% of the female patients were treated successfully; 94% of the cadaver-donor and 80% of the lilving-donor transplants responded successfully. The one-year rejection rate after OKT3 was 50%, adn 38% of rerejection episodes were treated successfully.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We compared the infections eccouraged in 23 renal transplant patioents given the monclonical anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of staroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factore predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclop9oraine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection eposode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 epidodes vs. 4,P=.02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)—Listeriasepsis (2), disseminated nocardiosis andMycobacterium tuberculosisinfection (1), cyutomegalovirus (CMV) pneumonia (1),Yersinainfection with severe dermatophytosis (1). adn Epstein-Barr virus-associated lymphoproliferative syndrome (1)—as compared with 1 case of mild CMV infection in the control group (P=.08). Trimethoprimsulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 withListeria) and 1, disseminated nocardiosis adnM tuberculosisinfection. These data suggest that OKT3 given for treatment of resistant rejecion in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-meiodated immunity. Prophylaxis with TMP-SMZ, which is sage, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may ne especially important during OKT3 therapy.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The charatersistics of 254 cadaveric kidndys were evaluated and the incidence of immediate function identified. The Belzer perfusate was used primarily (n=140) and secondarily (n=14) in conbination with pulsatile machine perfusion. These two groups were compared with a previous group of kindneys machine-perfused with silica gel (cryoprecipitated human plasma). The incidence of immediate function of the group primarily perfused with Belzer perfusate was statistically significantly improved over that of the silica gel. The secondarily perfused Belzer group, “imported” kidneys previously preserved with simple cold storage, had notably longer periods of preservation adn higher resitances on the machine. However, 100% of this group functioned immeidately. Other dindings in this study show that the Belzer perfusate allows for improved parenchymal function posttransplant, as noted by a more rapid clearance of serum creatinine posttransplant. When comkkparing the immediate function group with those suffereing early dysfunction, there is a statistically significant increased resistance on the machine in the latter group. This allows for prediction of immediate function based on perfusion characteristics of the kidney.The Belzer perfusate, comosed of metabolic substrates for high-energy phosphate production, improves the incidence of immediate function in machine-perfused kidneys, as well as improved qualitative function posttransplant. It also is effective as a “rescue” mechaniosm in previously simple cold-stored (ATP-depleted) kidneys.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The immunocuppressive action of cyclosporine in transplantation (Tx) is thought to be due to its potent inhibition of lymphokine production by T cell. Several studies have shown a decrease in interleukin 2 (IL–2) adn interferon-Gamma (IFN-G) production of renal Tx recipients on CsA treatment and have suggested that increased in lymphokine production can be correlatede with rejection epidosodes.In this study we measured IL-2, IFN-G, and lymphotoxin (LT) production by mitogen-stmulated peripheral blood lymphocytes in eight renal Tx recipients before and at various times after Tx. IL-2 production was significantly (P<0.05) decresed by one week post-Tx compared with pre-Tx and normal levels. IFN-G production was significantly (P<0.05) decreased by one week post-Tx, after which time it returned to normal. LT production was not decreased post-Tx compared with pre-Tx or normal levels. Lymphokine production was measured every 48–72 hr in the first month post-Tx, when we failed to detect any correlation between incresed in productinin any of the three lymphokines and rejection episodes. A further group of patients were studied in whom the production of all three lymphokines was measured at the time of diagnosis of rejection adn after treatment for rejection. In only 3/5 patients did IL-2 production decrease with a return to stable graft functio, while IFN-G production did not alter in these patients. Interestingly LT production increased significantly (P<0.05) after treatment. We conclude from these studies that the usefulness of lymphokine determinations for the diagnosis of allograft rejection remians unproved.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Cyclosporine-treted recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n=5308). The one-year survival rate for non-transfused recipients (n=709) was significantly lower at 69% (P<0.001). The transfusion effect was larger in black reciopients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not dignificantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero-DR-mismatched grafts. However, transfusions accounted for increased of 10%, 14%, adn 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens,l respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused revcipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplnats in Southern California, as compared with 10% in transplanted patients, suggesting a tendencey to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these date, we suggest that high survival of primary kidney allografts in th ecyclosporine era can best be maintained by the continued use f pretransplant transfusions for the majority of recipients— or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Cyclosporine (CsA level monitoring in renal transplant recipients has been thought to aid in separating clinical episodes of nephrotoxicity from rejection. Twenty-four-hour CsA pharmacodynamic profiles were obtained from 85 consecutive primary renal transplant recipients in the immediate peritransplant period in order to detrmine the value of this test in predicting subsequent episodes of nephrotoxicity or rejection. All patients were treated with sequential antilymphoblast globulin/CsA following transplantation. Serum samples from each recipient were analyzed for CsA level estimated by radioimmunoassay (RIA) four days after initiation of a daily single oral CsA dose (10mg/kg/day). A total of 52 episodes of rejection and 303 episodes of nephrotoxicity occurring within the first six months posttransplant were correlated with selected parameters from the immediate posttransplant CsA kinetic profile. For each profile these parameters were maximum CsA level, time to maximum CsA level, minimum CsA level, 95% clearance during the 24 hr following ingestion of CsA. No significant correlation was found between any of these parameters and either the incidence of frequency of rejection or nephrotoxic episodes, as determined by least-squares linear regression analysis. Furthermore, following a single oral dose of CsA (10 mg/kg/day), no correlation could be found between the dose and the absorption, accumulation, metabolism, and clearance of the drug. In conclusion, maximum Csa level, time to maximum CsA level, minimum CsA level, 95% clearance time of CsA, and total CsA accumulation and clearance measured from CsA kinetic profiles cannot be correlated with or predict the incidence of rejection or nephrotoxic episodes that subsequently occur during the first six months following renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

No significant difference in any measure of IF was found between all CsA+vs. CsA-patients, although both groups showed a highly significant increase in IF compared with control pretransplant donor biopsies. Similarly, no differences in tubular changes or the patterns of fibrosis were identified between CsA groups. However, since the mean interval between transplantand biopsy was significantly (p<0.04) greater for the CsA-group, measures of creatining and If were nonrmalized by the time interval between transplant and biopsy, and were stratified into biopsies obtained before or after 6 months posttransplant. By this stratification and normalization, both the baseline creatinine (P<0.01) and the degree of IF as measured by morphometry (P<0.04) were significantly higher in the CsA+group, but only for biopsies obtained >6 months posttransplant. Evaluation of biopsies > months posttransplant normalized by interval showed no suggested differences between the CsA+and CsA-groups in terms of creatinine levels or any measure of IF. tubular epithelial changes were not different in the CsA+and CsA-groups within either period. These results suggest that CsA therapy is not associated with increased interstitial fibrosis in renal allografts prior to 6 months posttransplant, after which there is a signivicant increase in fibrosis relative to patients not receiving CsA.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID