Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with renal transplants that survive the first year often ask about the chance of long-term function. We studied 1850 patients with primary transplants from June 7, 1963 to September 1, 1988 who had graft survival of greater than 1 year. Patients were grouped by donor type, diabetic status, and whether or not they received cyclosporine (CsA). Half-life (T1/2) was used to compare long-term survival rates. We determined the long-term graft survival inclusive and exclusive of death with function (DwF) in order to study all patients and to direct attention to immunologic losses. Pre-CsA, DwF was the major cause of graft loss in each cohort. Cause of DwF was cardiovascular (49%), infection (26%), and cancer (14%). The percentage of patients experiencing DwF was much higher in the pre-CsA group vs. the CsA group: HLA-identical living related donor, 16% vs. 3%; non-HLA-identical LRD, 22% vs. 5%; and cadaver donors, 26% vs. 11%. T1/2 for 711 transplants to diabetics (DM) was 9.01 +/- .54 years, while for transplants to 1139 nondiabetics (NDM) T1/2 was 13.57 +/- .68 (P less than .05). When DwF is excluded (DwFex) DM T1/2 = 23.5 +/- 2.69 and NDM T1/2 = 22.2 +/- 1.55 (NS). Overall, for HLA-identical transplants (n = 297) T1/2 = 26.13 +/- 3.35 and DwFex T1/2 = 104.3 +/- 28.93. Nonidentical LRD (n = 845) T1/2 = 11.25 +/- .61 and DwFex T1/2 = 19.37 +/- 1.55. For CAD (n = 701) T1/2 = 9.10 +/- .54 and DwFex T1/2 = 17.49 +/- 1.65. Comparing pre- and post-CsA cohorts, CsA has not resulted in significant improvement in long-term graft survival by T1/2 analysis with DwFex. It appears that overall long-term graft survival has improved with the introduction of CsA. Much of the improvement may be attributed to better first year graft survival and a reduction in cases of DwF. DM patients have an equal opportunity for long-term graft survival if they do not die from other causes. Excluding DwF, especially as an older population is transplanted, is important in determining chances of immunologic loss. Use of this type of analysis suggests that long-term outlook for 1-year graft survivors is excellent.
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PMID:Long-term outlook for renal transplant recipients with one-year function. "Doctor, what are my chances"? 198 80

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry crossmatches (FCXM) and correlated the results with primary cadaveric and retransplant graft survivals. In addition, we treated the XM sera with the reducing reagent dithioerythritol (DTE) to discriminate IgM from IgG immunoglobulin reactivity. For the 166 CsA-Pred-treated primary cadaveric renal allograft recipients the 1-year graft survival rate following an NIH-NEG XM was 81%. NIH-XM-NEG recipients who were also AHG-XM-NEG displayed an 82% 1-year graft survival as well. In contrast, NIH-NEG, but AHG-POS XM primary CAD recipients displayed a significantly reduced graft survival rate of 67%. Treatment of AHG-POS XM sera with DTE-delineated DTE/AHG-NEG and POS crossmatches associated with significantly different graft survivals of 83% and 0%, respectively, for these primary recipients. Flow cytometry XM results did not improve on the AHG-NEG or DTE/AHG-NEG XM primary graft survivals. These results were seen whether testing pre-Tx or historical (Hx) sera. For Re-Tx recipients an AHG-NEG XM resulted in significantly improved graft survival compared with the NIH-XM-NEG results. The overall 1-year graft survival rate for the 70 Re-Tx recipients studied was 64% (following a NEG pre-Tx NIH-XM). Re-Tx recipients with an AHG-NEG XM displayed an improved graft survival compared with NIH-XM-NEG recipients (77% vs. 64%, P less than 0.05) and with AHG-POS recipients (77% vs. 36%, P less than 0.01). However, treatment of Re-Tx, AHG-POS sera with DTE resulted in comparably poor graft survival rates of 31% and 50% for DTE/AHG-NEG and POS crossmatches, respectively. A FCXM did not improve on the results of Re-Tx graft survival following an AHG-NEG XM. These results were obtained whether testing pre-Tx or Hx sera. HLA matching, PRA, and the time the first Tx was lost did not influence the Re-Tx graft survival outcome following an AHG-NEG XM. Therefore, successful primary cadaveric renal allograft survival can be accomplished following either an AHG-NEG XM or an AHG-DTE-NEG XM. Re-Tx graft survival is significantly improved following an AHG-NEG XM. Re-Tx recipients with an AHG-POS XM who are either DTE/AHG-POS or -NEG display reduced graft survivals compared with AHG-NEG Re-Tx recipients.
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PMID:AHG and DTE/AHG procedure identification of crossmatch-appropriate donor-recipient pairings that result in improved graft survival. 199 22

1. The experience of 3,183 transplants between June 7, 1963 and September 30, 1990 at the University of Minnesota was reviewed. 2. Patients were divided into 4 historical periods-each era was associated with improved outcome. 3. As results have improved, the proportion of patients less than 5 years old and the proportion greater than 50 years old have increased. Type I diabetes has become the most common cause of renal failure in patients transplanted here. 4. The most important variable leading to improved outcome was donor source. Both HLA-identical and HLA-nonidentical LRD transplants have better outcome than CAD transplants (p less than 0.0001). 5. Multivariate analyses were done to determine risk factors for survival: a) in the first year, and b) in subsequent years. In the first year, age greater than 50, diabetes, and retransplantation had an adverse affect whereas LRDs and CsA immunosuppression were beneficial. Similar factors affected survival after the first year. HLA mismatch had no impact. 6. When death with graft function was excluded, diabetes and age greater than 50 were no longer risk factors, suggesting that the excess graft loss in these groups was due to patient death. 7. Chronic rejection and death with function remain the predominant causes of graft loss. 8. As protocols have evolved, results have improved, and previously "high-risk" patients are being successfully transplanted. Future efforts should be directed at decreasing graft loss from rejection and death with function.
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PMID:Lessons learned and future hopes: three thousand renal transplants at the University of Minnesota. 210 47

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.
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PMID:The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients. 283 Jun 86

CsA-Pred therapy yields equivalently good patient survival for LRD and 2 degrees CAD versus 1 degree CAD transplants. There is a long-term graft survival advantage for LRD versus 1 degree CAD transplants (5 years; 83% vs 58%). 2 degrees CAD transplants have inferior graft survival when compared with 1 degree CAD grafts (one year; 78% vs 67%). Multiple donor factors adversely affecting graft outcome include increased warm and cold ischemia times, pulsatile perfusion, use of pressors or diuretics in the donor, donor age less than 10 years, donor blood transfusions, and kidneys shipped from other centers. Recipient factors adversely affecting graft outcome include retransplantation and CMV infection as well as noncompliance with therapy. HLA-matching and pretransplant blood transfusions have not contributed in a statistically significant way to graft outcome although they may affect the quality of graft function at this center. Immunosuppressive therapy with CsA-Pred must be tailored to the individual patient. Continuous IV CsA infusion in the preoperative period and slow steroid taper impact favorably on graft outcome. The complications of CsA therapy include neuroectodermal toxicity, hepatotoxicity, and most importantly, nephrotoxicity. Other problems unique to CsA-Pred therapy include hypertension, delayed graft thrombosis, and de novo hemolytic uremic syndrome. Hepatotoxicity may eventuate in biliary and pancreatic complications necessitating surgical therapy. The overall incidence of infection and neoplasm remains low with CsA-Pred therapy. The use of therapeutic trough CsA level monitoring, as well as pharmacokinetic and pharmacodynamic analyses may assist in clinical decision making regarding administered doses, dosing interval, and discrimination between rejection and nephrotoxicity.
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PMID:Factors determining renal transplant outcome at the University of Texas at Houston. 315 93

1. There have been 1,426 renal transplants performed at the University of Minnesota from January 1, 1980 through August 31, 1988. CsA+P was used by 260 adult recipients, CsA+P+AZA(+ALG) by 536. 2. In general, there are no significant differences in actuarial graft or patient survival rates between the 2 CsA protocols. This is true for all adults, for all adult CAD recipients, and for a matched control group of adult CAD recipients. 3. Cox's proportional hazards regression model also indicates that there is no significant difference between the 2 CsA regimens. Donor type, number of transplants, and age at transplant influence graft survival in all adult recipients. The use of LRD is still indicated in the CsA era. Diabetic status, age at transplant, and number of transplants affect patient survival. The model fits the observed data quite well. 4. Actuarial analysis and Cox regression failed to document a beneficial effect of HLA-A, B, and DR matching in patients receiving either CsA protocol. Our data do not support the HLA matching point system currently used by UNOS or the Terasaki proposal to give points based on mismatching. 5. A matched control analysis of adult CAD recipients indicates that CsA+P+AZA+ALG has alleviated the problems of our CsA+P protocol without lowering the graft and patient survival rates. Thus, the sequential therapy group has equivalent graft and patient survival rates but shorter duration of ATN, lower serum creatinine levels at 1 year, and fewer patients who require modifications of protocol. Sequential therapy is our treatment of choice.
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PMID:A comparison of two cyclosporine protocols at the University of Minnesota. 315 98

CsA has improved the outcome of renal allotransplantation with CAD and LRD kidneys. CsA mitigates risk factors heretofore presenting substantial obstacles to CAD transplantation: HLA matching, pretransplant splenectomy, extensive numbers of conditioning blood transfusions, and old age. In LRD transplantation, CsA obviates the need for donor-specific transfusions in the haploidentical situation, and for prednisone in the HLA-identical setting. The incidence of drug-induced nephrotoxicity beyond six months is 30% with the degree of dysfunction proportionate to the degree of histo-incompatibility, suggesting that subclinical allograft rejection due to overzealous dose reduction may compromise allograft function. At present, total conversion from CsA to Aza appears ill-advised; even patients who never suffered allograft rejection under CsA therapy frequently lose their allograft when the inferior level of Aza suppression is substituted. Drug-induced hypertension, a modestly significant factor, diminishes further by two years posttransplant. The benefit of CsA therapy is a reduced incidence of 19% initial and 10% recurrent rejection episodes. Of great importance is the observation that 17% of rejection episodes followed patient noncompliance. Further, the incidence of bacterial infections was greatly reduced, and viral infections modestly lessened. Only the occurrence of pneumocystis carinii was increased, but 92% of patients survived in spite of serious pulmonary infection. Development of a consistent CsA regimen has reduced the median initial hospitalization to 12.5 days for LRD and 14 days for CAD, a level well within the range stipulated for the Disease-Related Guidelines of the Medicare Program. Furthermore, readmission is less frequent; one-third of patients never reenter the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of cyclosporine on renal transplant practice at the University of Texas Medical School at Houston. 392 60

We report our experience with 25 living-donor and 427 cadaveric-donor kidneys followed for over 6 years. Patient survival exceeds 90% at 5 years for all recipients. Overall one-year and 5-year graft survival rates were 82.7% and 65.5%, respectively. Approximately one-third of CAD were of extreme age (eg, < or = 10 and > or = 60 years old). One-year and 5-year GS rates of this group were 72.2% and 54.8%, respectively. Kidneys from elderly donors probably should be given to age-matched recipients. Infant en bloc kidneys had good GS. They also adapted well their growth and function to adult recipients and should be used more frequently to alleviate the organ shortage problem. HLA mismatches, transplant PRA level, original kidney disease, and immunosuppressive regimens significantly affected the GS. Race, sex, cytomegaloviral antibody states, unacceptable antigens, length of pretransplant dialysis, and CAD cold ischemic time had no significant effect on GS.
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PMID:Renal transplantation at Allegheny General Hospital with special reference to the use of extreme-age cadaveric donors. 754 42

Previous studies suggest stable renal transplant recipients can have either prednisone (P) or cyclosporine withdrawn; however, 30% of these patients undergo rejection requiring reinstitution of P or CsA. Some patients return to baseline creatinine levels, while others either stabilize at a higher creatinine level or lose their graft. It would be ideal to establish immunologically based criteria for selecting patients who can be successfully withdrawn or tapered from immunosuppression. We have investigated the development of donor antigen-specific hyporeactivity by using donor cells and/or homozygous typing cells defining the HLA-Dw specificities of the donor cells as stimulator cells in the mixed lymphocyte culture (MLC) and comparing the pre- and posttransplant responses of peripheral blood mononuclear cells from 199 kidney transplant recipients. Of these, 27% of the haploidentical living-related donor and 25% of the cadaver recipients developed in vitro donor antigen-specific hyporeactivity. The LRD recipients who did so have lower mean creatinine levels at 6, 12, and 24 months posttransplant (1.3, 1.3, and 1.2, respectively) than those who remained responsive to the donor antigens (1.6, 1.7, and 1.8) (P < 0.05). However, no differences in the mean creatinine levels were observed between CAD recipients who developed donor antigen-specific hyporeactivity and those who remained responsive. Rejection episodes were common in all groups in the first 3 months posttransplant; however, recipients who developed donor antigen-specific hyporeactivity tended to experience fewer rejection episodes after 3 months posttransplant. The percentage of recipients who remained rejection-free after 3 months post-transplant was 95% for CAD recipients who developed donor antigen-specific hyporeactivity vs. 83% for those who remained responsive. Only 1 hyporesponsive recipient (0/15 LRD; 1/20 CAD) developed chronic rejection vs. 12 (5/41, LRD; 7/60, CAD) recipients who remained responsive. For those with graft function at 3 months (when hyporesponsiveness was first determined), the actuarial 36-month graft survival was higher in the hyporesponsive (92%, LRD; 94%, CAD) than in responsive groups (LRD, 76%; CAD, 91%). No differences in the degree of HLA-DR mismatching (MM) were observed for the LRD hyporesponsive (1.20 DR MM) vs. reactive (0.98 DR MM) groups or for the CAD hyporesponsive (1.35 DR MM) vs. reactive (1.30 DR MM) groups. Donor antigen-specific hyporeactivity could not be determined (UND) for 30 of the LRD recipients and 33 of the CAD recipients due to lack of mismatching for DR antigens (0.03 DR MM and 0.25 DR MM, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence that improved late renal transplant outcome correlates with the development of in vitro donor antigen-specific hyporeactivity. 768 34

The development of accelerated transplant-related coronary artery disease (T-CAD) is the major obstacle to long-term survival of cardiac allografts. We have investigated the role of various demographic and immunologic parameters as prognostic indicators of T-CAD in a population of 274 heart allograft recipients. Our data demonstrate that patients who experience more than 1 episode of acute rejection per year and/or develop antidonor HLA antibodies are at increased risk of developing T-CAD. Using HLA-A2 as a marker for the release of soluble HLA antigens from the donor, we established that recipients displaying circulating donor alloantigens for more than 26 weeks following transplantation are at increased risk of developing T-CAD (P=0.008). This association suggests that the release of alloantigens from the allograft is indicative of chronic injury and/or that it stimulates chronic rejection via the indirect allorecognition pathway. Our findings indicate that patients at risk of developing T-CAD can be identified by monitoring the release of donor alloantigens and production of antidonor HLA antibodies following transplantation.
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PMID:Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. 861 Mar 82


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