Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delayed graft function (DGF) may be associated with diminished kidney allograft survival. We studied the risk factors that lead to nonimmediate function of a renal allograft and the consequences of DGF on short- and long-term renal transplant survival. Data from the U.S. Renal Data System were used to measure the relationships among cold ischemia time, delayed graft function, acute rejection, and graft survival in 37,216 primary cadaveric renal transplants (1985-1992). These relationships were investigated using the unconditional logistic and Cox multivariate regression methods. Cold ischemia time was strongly associated with DGF, with a 23% increase in the risk of DGF for every 6 hr of cold ischemia (P<0.001). Acute transplant rejection occurred more frequently in grafts with delayed function (37% vs. 20%; odds ratio=2.25, P=0.001). DGF was independently predictive of 5-year graft loss (relative risk=1.53, P<0.001). The presence of both early acute rejection and DGF portended a dismal 5-year graft survival rate of 35%. Zero-HLA mismatch conferred a 10-15% improvement in 1- and 5-year graft survival regardless of early functional status of the allograft. However, the 5-year graft survival rate in HLA-mismatched kidneys without DGF was significantly higher than that of zero-mismatched kidneys with DGF (63% vs. 51%; P<0.001). DGF independently portends a significant reduction in short- and long-term graft survival. Delayed function and early rejection episodes exerted an additive adverse effect on allograft survival. The deleterious impact of delayed function is comparatively more severe than that of poor HLA matching.
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PMID:Delayed graft function: risk factors and implications for renal allograft survival. 952 Dec 18

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.
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PMID:Highly successful long-term outcome of kidney transplantation in Chinese recipients: an enhancing race effect? 919 39

1. One-year graft survival rates for recipients of cadaver kidney transplants improved from 75% in 1988 to 83% in 1991 (p < 0.001). The one-, 5-, and projected 10-year graft survival rates for cadaver donor transplants performed in 1991-1995 were 84%, 60%, and 43% respectively. 2. One-year graft survival rates for recipients of living donor transplants also improved from 89% in 1988 to 93% in 1991 (p < 0.001). The one-, 5-, and projected 10-year graft survival rates for living donor kidney transplants performed in 1991-1995 were 92%, 75%, and 62% respectively. 3. Diabetic patients received one-quarter of the cadaver kidneys transplanted from 1991-1995 and one third of diabetic patients received a simultaneous pancreas (SPK) transplant. One- and 5-year graft survival rates were 81% and 54% for diabetics receiving a kidney transplant and 85% and 67% for SPK recipients, respectively. Patient survival was 10% lower for recipients of a kidney only transplant. 4. Sensitization to alloantigens, whether by pregnancy, transfusion, or graft failure resulted in about a 5% increased risk of early graft failure. Patients who developed broadly reactive anti-HLA antibodies before their first transplant had the same 5-year graft survival rate (60%) as unsensitized patients. Retransplanted patients who had not developed broadly reactive antibodies also had a 60% 5-year graft survival rate, compared with 50% for those with > 50% PRA. 5. Blacks received one-quarter of cadaver kidneys transplanted in 1991-1995. The one-year graft survival rate for Black first transplant recipients was 83% compared with 84% for Whites. After the first year, the graft loss rate among Blacks was almost double that for other racial groups (5.8 year half-life vs 11.3 years for Whites, p < 0.01). The 5-year graft survival rate was 49% among Blacks and 63% for Whites. Asian recipients had the highest one- and 5-year graft survival rates (89% and 70%, respectively). 6. Shared kidneys had a longer average cold ischemia time (30 hr) than kidneys transplanted locally (21 hr). Fewer than half of shared kidneys were transplanted to HLA-matched recipients. The 5-year graft survival rate for shared kidneys with zero or one HLA antigen mismatched was 68% compared with 59% for shared kidneys with more than 3 antigens mismatched and for locally transplanted kidneys (p < 0.001). 7. The distribution of living donor relationships has changed substantially. When comparing transplants performed in 1988-1989 with those performed in 1994-1995, the number of living donor transplants increased by 80%, the fraction of offspring-to-parent grafts increased from 9-15%, the fraction of genetically unrelated donors increased from 4-10%, and the fraction of distant relatives increased from 2-6% of the living donor transplants. 8. The results of living donor transplants generally followed the degree of HLA compatibility. The one-year survival rate for HLA-identical sibling grafts was 96%, followed by 92% for one-haplotype matched sibling, parent and offspring donor transplants, 90% for unmatched sibling donors and 88% for spousal donors. Other unrelated donor transplants had a slightly higher one-year graft survival rate of 92%, which was more similar to the one-haplotype matched grafts.
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PMID:The UNOS Scientific Renal Transplant Registry. 928 55

1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United States. 2. SEOPF centers transplanted better-matched kidneys than the rest of the nation despite transplanting a significantly larger percentage of "hard-to-match" black recipients. 3. Within SEOPF centers, a shared kidney was almost twice as likely to be a good match (zero-3 HLA antigen mismatches) as was a local kidney. 4. Within SEOPF centers, well-matched kidneys (zero-3 HLA antigen mismatches) had significantly better graft survival than did poorly-matched (4-6 HLA antigen mismatches) kidneys. 5. SEOPF centers had one-, 2- and 3-year graft survival rates comparable to those of the rest of the nation. 6. SEOPF centers have proven the efficiency of ROP trays in predicting final crossmatch results for shared kidneys. 7. The SEOPF High Grade Match (HGM) algorithm has been successful in transplanting highly sensitized (current PRA > 40%) recipients. 8. The use of ROP trays in well-matched, highly sensitized recipients resulted in improved kidney availability. 9. Graft survival of HGM recipients was comparable to that of non-HGM recipients. 10. Despite longer cold ischemia times for HGM kidneys, there was no increased incidence of delayed graft function in these kidneys. 11. The HGM program accounted for 8.1% of the participating centers' activity and, thus, has not adversely impacted the majority of the centers' other patients. 12. The one- and 2-year graft survival data for HGM transplants were in accordance with the expected rates and were not statistically different from those of non-HGM transplants.
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PMID:Kidney sharing by centers of the South-Eastern Organ Procurement Foundation. 928 62

1. GENERAL: Here we updated our analysis of the UNOS Kidney Registry for the compound effects of 26 transplantation factors on graft survival within 2 consecutive posttransplantation risk periods. During the early risk period, 83,867 kidney-only recipients were followed through one year, and, in the second (chronic) risk period, 66,358 recipients whose grafts survived beyond one year were followed for 5 years after transplantation. 2. SHORT-TERM EFFECTS: From the analysis, the top (< 2% of assignable variation) factors influencing one-year graft survival rates were ranked as follows: 1) living-related and living-unrelated donor transplants were preferred; 2) some transplant centers had outstanding results; 3) kidneys from stroke victims displayed poor results; 4) recipients with PRA > 80% demonstrated poor survival; 5) patients transplanted before 1991 had poor results; 6) increasing numbers of HLA-ABDR mismatches decreased survival; 7) cold ischemia times beyond 24 hours diminished survival; 8) kidneys from younger and older donors impaired survival; 9) regrafting was detrimental, 10) Asians and Hispanics enjoyed superior results; 11) recipients with restricted activities pretransplantation were at higher risk of early graft failure; and 12) high (> 30 kg/m2) body mass recipients demonstrated lowered rates. 3. LONG-TERM EFFECTS: Fewer net factors influenced graft survival beyond 1 year through 5 years. The following 9 factors, each explaining > 2% of the assignable variation in conditional 5-year graft survival, were ranked and yielded poor results: 1) older (> 65) donors; 2) Black recipients; 3) poor transplant centers; 4) male recipients; 5) kidneys from cadaver or living parental donors; 6) transplantation prior to 1991; 7) stroke donors; 8) non-zero HLA-AB mismatched transplants; and 9) teenage recipients. 4. IMPACT ON KIDNEY ALLOCATION: This UNOS data analysis combined with other recent multi-center studies suggest that the criteria for kidney allocation need contain just 2 components in order to maximize long-term survival-an immunologic factor (avoiding HLA mismatches) and a non-immunologic factor (a senior citizens pool to receive older donor organs).
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PMID:A multi-factor analysis of kidney graft outcomes at one and five years posttransplantation: 1996 UNOS Update. 928 81

The distribution and effectiveness of different immunosuppression protocols among recipients of first cadaver donor renal transplants reported to the UNOS Scientific Renal Transplant Registry whose graft survived at least 14 days after transplantation were analyzed. The results showed that between 1988-1993, 50-60% of recipients received triple therapy regimens including cyclosporine, azathioprine and prednisone (CAP). An additional 20% received CAP with antibody induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of other drug combinations which include FK506 and, more recently, Neoral and mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the immunosuppressive protocol. The 3-year graft survival rate was 75% under cyclosporine-based protocols, but was 79% for more recent recipients treated with FK506 (p = 0.015). Antibody induction protocols were not used more frequently for high-risk patients, including those with broadly reactive anti-HLA antibodies, pediatric recipients, transplants with delayed graft function and those with prolonged cold ischemia times. When induction therapies were reported for these higher risk transplants, there was no noticeable improvement in graft survival rates after excluding failures within the first 2 weeks. Any benefit of antibody induction must therefore be manifest with the first 2 weeks after transplantation. Induction protocols significantly reduced the incidence of rejection episodes (prior to hospital discharge) from 31% for those treated with CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those given induction had at least one rejection between discharge and 6 months compared with only 18% of those treated with CAP without induction (p < 0.01). Although graft outcomes might be significantly influenced by the dosing and timing of immunosuppressive drugs, among the different combinations of drugs analyzed, only FK506 resulted in improved graft survival and half life. With the rapid proliferation of newer drugs and immunosuppressive strategies during 1996, it will be interesting to follow the course of these very recent transplants with regard to the effectiveness of changing immunosuppression.
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PMID:Immunosuppressive regimens and their effects on renal allograft outcome. 928 82

1. HLA matching exerts a profound influence on graft outcome. The difference in 3-year graft survival rates between best and worst matched cases was 17% for first grafts and 18% for retransplants. This HLA matching effect persists despite recent improvements in graft outcome. The matching effect at 3-years was 12% for transplants since 1991. 2. Surprisingly, HLA matching is especially important for recipients over age 60. The increase in the HLA matching effect to 20% in patients older than 60 can be attributed to the additive effects of HLA matching on both functional and patient survival. Consequently, graft survival for zero-MM recipients is similar for patients older and younger than age 60. 3. The difference in 3-year survival between zero and 0-MM kidneys was 10% for White and 15% for Black recipients. 4. Transplants with zero-broad but split A,B mismatches had graft outcomes similar to one-A,B,DR MM kidneys. Split DR MM did not affect the outcome of zero-MM kidneys. 5. HLA-matched transplants can be classified according to the degree of identity between the donor and recipient: 6-antigen match, phenotypic match, and zero-MM. Outcome for zero-MM was lower in transplants before 1990, but the 3 types have similar outcomes in recent transplants. The change in UNOS matching policy in 1995 to include zero-MM kidneys doubled the number of shared kidneys. 6. HLA typing from over 150 centers resulted in an error rate for shipped kidneys of less than 5%. Donor antigens retyped at the recipient center resulted in identical antigens for 70% of cases, a broad DR MM for 2.2%, and an A,B MM in 2.6% of the retyped cases. 7. Although increasing cold ischemia time (CIT) had a deleterious effect on survival of MM kidneys, no effect was seen for zero-MM kidneys. 8. An effect of a possible sex-linked minor histocompatibility antigen was demonstrated with improved outcome for male to male zero-MM cadaveric and parent-to-child transplants. 9. Zero-MM kidneys from pediatric donors and donors older than 60 years of age had poorer outcome than MM kidneys before 1991, but the recent experience shows a matching effect even with these marginal donors.
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PMID:HLA matching. 928 84

There are only few data available regarding the immunological mechanisms for cerebral infarction. The aim of this study was to find out the humoral and cell-mediated immunity under the conditions of focal brain ischemia (CI). As a method for humoral immunity, the complement consumption test against a panel of 8 antigens, quantitative analysis of immunoglobins and fractionized sedimentation of erythrocytes were used in the group of pts with CI, and the group of atherosclerotics (AS) and hypertonics (VH), potential victims of focal brain ischemia. It was found that the occurrence of antibodies against the whole panel of antigens in the group of CI is significantly higher as compared with the healthy controls, but it is lower than that in the group of AS and VH. The occurrence of antibodies exclusively against only brain antigens and that in CSF is similar. No correlation to the location of ischemic lesion and the degree of neurological deficit score was found. These findings didn't change in 2 and 4 weeks as well as in 1 year after the onset of CI. The quantitative analysis of immunoglobins revealed statistically higher levels of IgA and lower levels of IgM in comparison with the controls. IgG were higher, but without statistical significance. Statistically significant higher levels of all immunoglobins in CSF were found. As similar trend of changes found also in the group of AS and VH. These results of humoral immunity confirmed by the results of fractionized sedimentation of erythrocytes with EP. The results can be interpreted as a possible change or disorder of central regulation of immunizing processes due to the latent (in AS and VH) of manifest (in CI) lesions of the brain. But the quality and quantity of this response might have been affected by the entire case history of the patients who survived cerebral infarction. The changes in immunity response of the organism in CI was shown also in cell-mediated immunity. The results a statistically significant increase in stimulatory (SI) as well as in immunoregulatory (IRI) indices in stroke patients under the age of 40. These findings didn't change 2 and 4 weeks after the onset of CL. An increase in IRI was due to the increase in Th lymphocytes. In the immune response of the organism in CI, the antiphospholipid antibodies (aPLs = anticardiolipin antibodies (aCL) and lupus anticoagulant--LA) play an important role. aCLs were present in 9.8% of the first stroke pts when compared to 4.3% in controls. The most common isotype of the antibodies we IgG. Of all first-stroke pts who were aCL positive only 8% had no other stroke risk factors (atrial fibrillation, diabetes, hypertension and other). aCLs are an important risk factor for the first stroke, mainly in the young, but also in the elderly. The presence of aCLs increases the risk for recurrent strokes. aPLs are not necessarily associated with the specific location of clinical stroke syndrome but they are in significant correlation to the occurrence of multiple strokes on CT (30:18%). None of the initially aCL-negative patients became aCL-positive during the time course of CI. These data support the idea that aCLs play a causal role in stroke (PROPTER HOC changes) rather than vice versa (POST HOC changes). From the therapeutic point of view, currently there do not exist any good treatment guidelines for preventing the second stroke. The analysis of HLA. antigen showed an increase in some HLA (A2, A28 etc.) and a decrease in others (A3, A9 etc.) in comparison with the controls. This might refer to the participation of genetic factors in the onset of CI.
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PMID:[Cerebral infarct and the immune response]. 933 23

The shortage of cadaveric donor kidneys for transplantation has forced a re-evaluation of the limits on donor age acceptability. However, as more kidneys from older donors have been transplanted, a significantly lower graft survival has been noted among their recipients. The impact of utilizing older donor kidneys and the relative importance of donor age with respect to other factors has not been clarified. A total of 43,172 cadaver donor transplants reported to the UNOS Scientific Renal Transplant Registry between 1987 and 1995 were the subjects of this study. Cox regression analysis was utilized to assess the joint effects on graft survival of donor age and HLA mismatch, recipient sex, race, age, original disease, donor death cause, cold ischemia time, and transplant year. Increased first day anuria, dialysis requirement, and discharge serum creatinine were noted with increasing donor age. Moreover, long-term graft and patient survival diminished as donor age increased. The 5-yr graft survival of zero HLA-A,B,DR mismatched kidneys fell steadily from 81% when the donor was aged 21-30 to 39% when the donor was over age 60. The reported causes of kidney transplant failure were remarkably similar for old and young donors. The best transplant results were obtained with zero HLA-A,B,DR mismatched transplants from young donors and the worst with older donor kidneys, regardless of HLA compatibility. We calculated that up to 21% of kidney failures resulted from insufficient renal mass due to age and were incorrectly attributed to chronic rejection.
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PMID:Significance of the donor age effect on kidney transplants. 936 25

ROP trays containing patient serum samples and distributed by the South-Eastern Organ Procurement Foundation (SEOPF) were instituted to increase the likelihood of transplanting potential renal recipients who are highly sensitized to HLA antigens. This study examines kidney distribution and transplant outcome to assess equitable placement and clinical function post transplant with and without the use of ROP trays. Data were collected over a 26-month period on the distribution of kidneys from 328 consecutive SEOPF donors from whom at least 1 kidney was procured. Shared kidneys were placed via the UNOS and SEOPF-variance computer match programs. Of 656 kidneys, 596 were placed into 582 recipients; 60 were not used. ROP trays were used in placement of 492 kidneys and were not used for placement of 104 kidneys. Outcome was determined for 435 kidneys transplanted into SEOPF recipients. Only 33 (6.9%) recipients with ROP tray use and 10 (9.8%) without were sensitized to HLA. A 10% increase in placement to the originally intended recipient was seen with ROP tray usage over kidneys placed without ROP tray use (p < or = 0.025). Recipients matched using ROP tray data averaged 29 positions higher on the match printout. There was no difference in tray use regarding placement of kidneys within or outside the donor's local UNOS region, nor was there a difference in mean HLA match of transplant pairs with and without ROP tray use, 3.2 and 3.1 antigens, respectively. Cold ischemia time was similar, 22.9 and 23.6 h, respectively, for kidneys placed with and without ROP trays. At post-transplant discharge, there were no differences in patient status, graft failure, rejection treatment, dialysis need, or urine output whether or not ROP trays were used. Significantly, however, plasma creatinine at discharge and at 12 months was lower for those placed with ROP trays (2.5 mg/dl and 1.7 mg/dl) vs (3.1 mg/dl and 1.9 mg/dl), respectively. During this time period, all kidneys transplanted with use of ROP trays functioned as well or better than those transplanted without ROP tray placement. Thus, the use of ROP trays appeared to have a beneficial effect in getting more recipients of higher priority transplanted with equivalent, if not better, graft function.
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PMID:Regional organ procurement (ROP) trays in renal allograft distribution and outcome. 936 47


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