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At least 19 recordsLinked to original sources
PubMed1982

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.

Adult↗
PubMed1992

Simultaneous kidney-pancreas transplantation versus kidney transplantation alone: patient survival, kidney graft survival, and post-transplant hospitalization.

This study compared patient survival, kidney graft survival, and post-transplant hospitalization between patients who received simultaneous kidney and pancreas (SKP) transplants and those who received a kidney transplant alone (KTA). A total of 3,168 diabetic end-stage renal disease (ESRD) patients, ages 18-45, who began their first ESRD treatment between 1981 and 1989 and received their first cadaveric kidney transplant between 1986 and 1989 were selected for study; patient and kidney graft survival were followed until 1 March 1990. Twelve percent (380) of these patients received SKP transplants. No statistically significant difference in patient survival was found between SKP and KTA patients (p = 0.86). Kidney graft survival was statistically significantly higher for SKP patients than KTA patients (p = 0.008). Post-transplant hospitalization rates were statistically significantly higher for SKP patients (p < 0.001), indicating potentially higher post-transplant morbidity among this group.

Adolescent↗
PubMed1997

Cytomegalovirus and HLA-A, B, and DR locus interactions: impact on renal transplant graft survival.

Graft failure rates for renal transplantations performed between 1989 and 1994 and recorded in the US Renal Data System database were retrospectively evaluated for interactions between cytomegalovirus and HLA-A, B, and DR loci. Twelve significant interactions were observed. There were significantly greater risks of graft failure for the total effect of cytomegalovirus and donor or matched HLA-DR9, recipient or matched HLA-B-51, and matched HLA-B13. We conclude that further study of renal transplants with these combinations of cytomegalovirus and HLA loci is needed to determine whether the observed interactions should be taken into consideration when matching donors with recipients.

Adult↗
PubMedDate not supplied

Neuron-enriched second trimester human cultures: growth factor response and in vivo graft survival.

Grafts of first trimester fetal tissue show limited survival and integration in the adult CNS. Alternative grafting strategies have been sought for treatment of neurodegenerative disease. We have developed cultures of human second trimester fetal tissues to study neuronal differentiation. Grafted into the SCID mouse striatum, aggregates of these cultures formed neuron-rich xenografts for at least 8 months. We examined the influence of various neurotrophic factors, including basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), transforming growth factor-beta 1 (TGF-beta1), and hepatocyte growth factor (HGF), on the growth and differentiation of neuronal and glial cell populations. BDNF promoted the survival and differentiation of second trimester neurons whereas bFGF exhibited a strong proliferative effect on precursors and the astroglial population. Our data suggest that second trimester human fetal cultures contain neuroprogenitor cells that can be directed to the neuronal lineage. This process may be amplified by treatment with BDNF, which we hypothesize could improve the long-term in vivo survival of neuron-enriched grafts.

Animals↗
PubMed1986

[Effect of T-cell depletion of the graft on graft survival and graft vs host disease].

A limiting dilution culture method has been developed which allows the detection of small numbers of residual marrow T cells following their depletion with the monoclonal antibody Campath-I and autologous complement. In seven consecutive patients the degree of T cell depletion obtained was 1.82 (1.27-2.82) log. The number of nucleated cells per kg decreased by 50% and the number of CFU-GM per kg decreased by 60%. In all except one case marrow cellularity was found to be satisfactory 3 weeks after the transplant. Peripheral engraftment of granulocytes (greater than 500/mm3 on day 20, greater than 1000/mm3 on day 27), lymphocytes (greater than 500 on day 39, greater than 1000 on day 66), platelets (greater than 20,000 and self-sustained after day 24) and red blood cells (day to last infusion = 19) indicated a delay in recovery of lymphocytes and possibly granulocytes, but not platelets or red blood cells, compared to the engraftment seen in non-T depleted patients. No correlation between nucleated cells infused, GFU-GM and engraftment was found. However, the extent of T cell depletion apparently affects lymphocyte, and possibly granulocyte, recovery. The delay in lymphoid engraftment is also reflected by nonresponsiveness to alloantigens during the first 6-9 months following marrow grafting in the absence of graft vs. host disease.

Graft Survival↗
PubMed2002

Graft survival and graft function of pediatric en bloc kidneys in paraaortal position.

BACKGROUND: En bloc kidneys from pediatric donors are regarded as questionable with respect to the safety and quality of the transplant outcome. Therefore, we retrospectively studied graft outcome and graft function of our 56 en bloc kidneys transplanted in paraaortal position between 1992 and 1999. METHODS: Graft outcome of en bloc kidneys (group A) was compared with graft outcome of single cadaveric adult donor kidneys (group B). Matched pairs were generated regarding HLA-missmatch, cold ischemic time, recipient age, body mass index, and systolic arterial blood pressure. RESULTS: Allograft survival rates of pediatric en bloc kidneys at 1, 3, and 5 years were significantly lower (group A: 78, 70, 70% vs. group B: 92, 92, 81%, P<0.05). Lower survival rate was caused by a higher number of graft losses in the early postoperative period (group A: 21% vs. group B: 4%, P<0.01) due to vascular complications. Main risk factor for graft loss was donor age of less than 12 months. Five years after transplantation serum creatinine of pediatric en bloc kidneys was significantly better than of adult kidneys (0.9+/-0.06 vs. 1.8+/-0.2 mg/dl, P<0.001). CONCLUSION: En bloc kidneys show a high percentage of graft survival with excellent long-term graft function. However, the early postoperative period carries a higher risk of graft loss in very young donors due to vascular complications. In the face of donor shortage en bloc kidneys from pediatric donors can successfully be transplanted in a paraaortal position.

Adult↗
PubMed2004

Studies of Pediatric Liver Transplantation 2002: patient and graft survival and rejection in pediatric recipients of a first liver transplant in the United States and Canada.

Studies of Pediatric Liver Transplantation (SPLIT) is a cooperative research network comprising 38 pediatric liver transplant centers in North America. Data from the 1092 patients who have received a first liver transplant since 1995 were analyzed for factors influencing patient survival, graft survival and acute rejection. The 3, 12, 24 and 36 month Kaplan-Meier estimates of patient/graft survival were 90.9/85.5, 86.3/80.2, 84.3/76.0, and 83.8/75.3% respectively. Univariate analysis identified initial diagnosis, type of graft (whole vs. living and cadaveric technical variant), growth failure and continuous hospitalization or ICU admission prior to transplantation as significantly influencing patient and graft survival. Subsequent multivariate analysis identified as risk factors for death: fulminant liver failure (RR = 3.05, p < 0.05), cadaveric technical variant grafts (RR = 1.95, p < 0.05), continuous hospitalization pre-transplant (RR = 1.79, p < 0.05), height deficit >2 s.d. from mean (RR = 3.22, p < 0.05). Risk factors for graft loss included: fulminant liver failure (RR = 2.27, p < 0.05), cadaveric technical variant grafts, (RR = 1.97, p < 0.05). Eleven percent of the 1092 patients were re-transplanted; vascular complications, particularly hepatic artery thrombosis (8.3% overall; 36.3% of graft failures), were responsible for the majority of re-transplants. Infection was the single most important cause of death (40 of 141, 28.4%) and was a contributing cause in 55 (39%), particularly with bacterial or fungal organisms. The cumulative Kaplan-Meier estimates of first rejection at 3, 12, 24 and 36 months were 44.8, 52.9, 59.1, and 60.3%. Initial immunosuppression with tacrolimus reduced the probability of rejection (RR = 0.62, p < 0.05). Eleven percent of rejections were steroid-resistant; chronic rejection led to 7 of 121 (5.8%) re-transplants. The SPLIT registry, in compiling data from a large number of centers, reflects the current outcomes for pediatric liver transplants in North America.

Adolescent↗
PubMed1997

Effect of delayed graft function on short- and long-term kidney graft survival.

Delayed graft function (DGF) has been identified as a predictor of poor long-term graft survival, but whether its effects are independent of rejection or final serum creatinine level is controversial. Based on the results of 57,025 first cadaver transplants reported to the UNOS Registry, we showed that: 1. Early acute rejection significantly lowered one-year graft survival rates by 8-9% in kidneys with early function (EF) (89% vs 80%; p < 0.001) or with DGF (72% vs 64%; p < 0.001). 2. DGF significantly lowered short- and long-term graft survival in patients without rejection (EF-1-yr graft survival rate of 89%, t1/2 of 9.5 years vs DGF-72% 1-yr graft survival rate, t1/2 of 6.7 years; p < 0.001). 3. Even when the discharge serum creatinine level was < 2.0 mg/dl with no rejection, DGF lowered graft survival (EF-1-yr graft survival rate of 93%, t1/2 of 10.4 years vs DGF-90% 1-yr graft survival rate, t1/2 of 7.6 years; p < 0.001). 4. Acute rejection, elevated discharge serum creatinine level (2-6 mg/dl) and older donor age (46-60 yrs) each lowered one-year graft survival rates in a stepwise fashion. There was exceptionally poor graft survival of kidneys from donors aged 46-60 with DGF, whether or not early acute rejection was present (with rejection-1-yr graft survival rate of 61%, t1/2 of 5.6 yrs vs no rejection-1-yr graft survival rate of 71%, t1/2 of 5.3 yrs). 5. Increasing cold ischemia time only decreased graft survival when there was no DGF and no rejection and had no significant effect on long-term graft survival. 6. Among recipients of HLA-matched cadaver kidneys, DGF lowered short- and long-term graft survival, even in the absence of early rejection (EF-1-yr graft survival rate of 93%, t1/2 of 14.8 yrs vs DGF-1-yr graft survival rate of 76%, t1/2 of 7.8 yrs). 7. DGF was associated with higher rates of acute rejection but impaired long-term graft survival even when rejection was absent and discharge creatinine was normal. These data support the hypothesis that DGF leads to an injury response that can reduce graft survival through antigen dependent and antigen independent mechanisms.

Adult↗
PubMed1977

The influence of presensitization on graft survival rate.

Graft survival rate was evaluated in 61 recipients with greater than 50 percent frequency of performed antibodies to selected panel cells. This includes recipients of primary cadaver grafts, secondary cadaver grafts, and living related grafts. Graft survival rate also was evaluated in 199 recipients with pretransplant antibodies reacting with 10 to 50 percent of panel cells and in nonsensitized patients. The results show that good graft survival can be obtained in many hyperimmunized patients, particularly in recipients of primary renal allografts (66 percent cadaver graft survival rate at 2 years). However, sensitization following rejection of an allograft appears to confer a less favorable prognosis. The nature of recipient presensitization and the precise specificity of each reactivity cannot always be explained. This is exemplified in three patients in whom broadly reactive lymphocytotoxic antibodies were not directed against HL-A antigens. Since the number of sensitized patients who await renal transplantation is increasing, there should be no hesitation in proceeding with transplantation, particularly with primary grafts. Emphasis, however, must be placed on frequent prospective recipient serum sampling so that transient high levels of cytotoxins do not escape detection and therefore can be easily selected out for cross-matching against potential donors.

Antibodies↗
PubMed2005

Risk factors for delayed kidney function and impact of delayed function on patient and graft survival in adult graft recipients.

The influence of delayed kidney graft function on allograft outcome is described controversially in the literature. The aim of the study was to evaluate possible risk factors for delayed graft function (DGF) and investigate the impact of DGF on short- and long-term renal allograft function. Two groups were formed: the first one consisted of patients who gained immediate graft function (IGF) (n = 64) after transplantation and the second group included patients with DGF (n = 31; with at least one dialysis needed in first week after transplantation). The DGF group had a statistically significant longer duration on dialyses prior to transplantation (DGF 54 vs. IGF 33 months; p < 0.05), on average more frequently a re-transplantation (DGF 1.7 vs. IGF 1.3; p < 0.01), a longer re-anastomosis time (DGF 52.9 vs. 44.2 min; p < 0.01), a lower systolic (DGF 136 +/-24 mmHg vs. IGF 158 +/- 25; p < 0.001) and diastolic blood pressure (DGF 78 +/- 14 vs. IGF 89 +/- 16 mmHg; p < 0.01) at admission to the hospital and a higher serum (S)-creatinine at discharge (DGF 2.5 +/- 1.6 vs. IGF 1.6 +/- 0.4 mg/dL; p < 0.01). Prior to transplantation the DGF group had more often advanced vascular diseases (DGF 29.0 vs. IGF 12.5%; p < 0.01) and these patients incurred more frequently new ones during the next 3 yr after transplantation (DGF 22.6 vs. IGF 6.3%; p < 0.001). After 3 yr the graft survival tended to be lower in the DGF group (DGF 74.2 vs. IGF 84.4%; NS), but this difference was not statistically significant.

Adult↗
PubMed1996

Alternate-day steroid dosing improves growth without adversely affecting graft survival or long-term graft function. A report of the North American Pediatric Renal Transplant Cooperative Study.

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effects of alternate-day (QOD) steroid dosing on growth, graft survival, and graft function in children with functioning grafts 12 months after transplantation. At 12 months after transplantation, 16.8% (337/2001) of transplant recipients were receiving QOD dosing. The basis for the selection of a steroid dosing regimen cannot be determined from registry data; however, the frequency of QOD dosing differed by donor source, race, age at transplant, and the occurrence of rejection episodes in the first year. The effect of the steroid dosing pattern on growth was evaluated in children continuously on either QOD or daily (QD) steroid dosing. The mean change in the standardized height scores from 1 month to 24 months after transplantation was significantly greater in those on QOD dosing (+0.5 +/- 0.06) than in those on QD dosing (+0.1 +/- 0.03). Using multiple regression analyses, better growth was associated with QOD dosing, recipient age less than 13 years, lower total steroid dose over 48 hr, and lower serum creatinine (all P < 0.001). Graft survival did not differ on the basis of the steroid dosing pattern. In a proportional hazards model for survival of living donor grafts after 12 months, graft survival was negatively associated with the use of QD dosing, black race, rejection episodes in the first year, and a higher serum creatinine at 12 months. The survival of cadaver grafts was negatively associated with the use of QD steroid dosing, recipient age less than 2 years, rejection episodes in the first year, and a higher serum creatinine at 12 months. In addition, the decline in graft function did not differ between those on QOD steroid therapy and those on QD therapy. We conclude that selected pediatric renal transplant recipients receiving QOD dosing have better growth than those receiving QD dosing without compromising allograft survival or function.

Adolescent↗
PubMed2001

The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice.

VX-497 is the first inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor generated in a structure-based drug design program specifically addressing the tolerability problems of currently available immunosuppressive drugs. The pharmacological activity of the compound has been examined in murine skin transplantation and graft versus host disease (GVHD) models. In the skin transplant study, trunk skin grafts from Balb/c mice were grafted onto C57Bl/6 mice. Mice were administered vehicle or VX-497 twice daily until day 10. Mean survival of skin grafts on vehicle-treated animals was 9.9 +/- 0.9 days. Graft survival was prolonged significantly in animals treated with VX-497 to 13.2 +/- 1.2 (p < 0.001, Kaplan Meier Log-Rank test) days in the 50 mg/kg group and 13.9 +/- 1.0 (p < 0.001) days in the 85 mg/kg group. In the GVHD study, 150 x 10(6) nonadherent splenocytes from B6 mice were injected intravenously into the F1 hybrid strain B6DBA/2. Groups of animals (n = 6) were administered vehicle or 50 or 100 mg/kg VX-497 b.i.d for 8 days. Animals were sacrificed and spleen weights and interferon-gamma (IFN-gamma) serum levels were determined by enzyme-linked immunosorbent assay. In addition, spontaneous spleen cell proliferation was measured using a 3H-thymidine uptake assay. Isografted F1 animals served as controls. GVHD developed in the vehicle-treated allografted F1 mice and treatment with VX-497 improved all manifestations of the disease significantly. The 2.9-fold increase in spleen weight in allografted animals was reduced to a 1.6-fold increase in the VX-497-treated mice. Serum IFN-gamma levels were increased 54-fold in the vehicle group while there was a 7.4-fold increase in VX-497-treated animals. Spontaneous spleen cell proliferation was increased 9.9-fold in the absence of VX-497 and there was a 3.5-fold increase in its presence. Thus, VX-497 has been shown to be effective in both a skin transplantation and a GVHD model in the mouse. The demonstrated pharmacological activity of VX-497 in these murine transplantation models warrants further evaluation of the drug in transplantation indications.

Animals↗
PubMed2002

[Cadaver renal transplantation and multivariate analysis for graft survival: a clinical review of 2 016 cases].

OBJECTIVE: To review kidney transplantation in the center and analyze the risk factors affecting long-term allograft survival. METHODS: Thirty-two relative variables were analyzed with SAS statistical software. Using Log-rank method, we investigated influence of these variables on short-and long-term survival of grafts. Kaplan-Meier analysis was used to estimate the 1-, 3-, 5-, 10-years graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess and rank the relative risk of potential variables. RESULTS: The 1-, 3-, 5-, 10-years graft survival rates were 83%, 75%, 66% and 48%. After excluding the patients died with functioning grafts, the 1-, 3-, 5-, 10 years grafts survival rate increased to 89%, 82%, 75% and 69%, respectively. The mean half-life was 8.78 +/- 0.14 and 14.09 +/- 0.20 years, respectively. By Log-rank analysis, factors affecting short- and long-term graft survival were identified as: renal function, duration of graft function became normal, cold-ischemia time, presence of acute rejection, delayed graft function, immunosuppressive regimen, complication, infection, anti-rejection therapy. Cox model multivariate analysis showed that there were 18 factors affecting graft survival. CONCLUSIONS: New immunosuppressive agents not only significantly increase short-term graft survival, but also have the better long-term outcome tendency. Making assurance to get high quality donor organ and minimizing the death with graft function may be the most feasible way to prolong graft survival at present.

Adult↗
PubMed1999

Focal segmental glomerulosclerosis in renal allografts with chronic nephropathy: implications for graft survival.

De novo focal segmental glomerulosclerosis (FSGS) in renal allografts most often is diagnosed in association with chronic allograft nephropathy (CN). In this study, we assessed the clinical and pathological variables that correlate with the presence of de novo FSGS and the implications of FSGS for the survival of grafts with CN. The study population included 293 renal allograft recipients (52 living related donor, 241 cadaveric donor) diagnosed with CN by biopsy more than 6 months after transplantation. Patients with recurrent FSGS or FSGS associated with other glomerulopathies were excluded. FSGS was present in 87 patients with CN (30%). FSGS was diagnosed more commonly in the following groups of patients: young (P = 0.04), black (P = 0.02), and those with elevated serum cholesterol levels (P = 0.002) and/or high-grade proteinuria (P < 0. 0001, all univariate analysis). FSGS was diagnosed later after transplantation than CN without FSGS (P < 0.0001), and FSGS correlated with the presence of arteriolar hyalinosis in the biopsy specimen (P = 0.04). Compared with CN without FSGS, FSGS was associated with significantly worse death-censored graft survival (P = 0.008, univariate Cox). In addition, when we analyzed all patients with CN, graft survival correlated by multivariate analysis with the following parameters: serum creatinine level (P < 0.0001) and proteinuria (P = 0.004) at the time of diagnosis, presence of FSGS (P = 0.03), and degree of interstitial fibrosis and tubular atrophy (CN score; P < 0.0001, Cox). Of interest, the use of lipid-reducing agents was also associated with improved graft survival in patients with CN (P = 0.0002, univariate Cox), although total lipid levels were not significantly less in patients receiving these drugs. In conclusion, de novo FSGS presents late after transplantation and in association with arteriolar hyalinosis, suggesting these lesions may be related to chronic cyclosporine toxicity. In CN, the presence of FSGS and the severity of interstitial fibrosis are negative independent predictors of graft survival. The possible relationship between lipid-reducing agents and graft survival clearly needs to be examined carefully in future studies.

Adult↗
PubMed1999

Impact of a preceding striatal excitotoxic lesion and treatment with ciliary neurotrophic factor on striatal graft survival.

The survival of grafted embryonic striatal tissue, dissected from the lateral ganglionic eminence, depends on the status of the host striatum. We found significantly larger volumes of surviving graft tissue and of striatal-like tissue (P-zone) within the graft, when the host striatum had been subjected to an excitotoxic lesion prior to transplantation surgery. Concomitantly the numbers of surviving grafted cells, assessed in both cresyl violet-stained sections and in sections stained with an immunohistochemical marker for striatal neurons, increased as compared to when graft tissue was placed in an intact unlesioned striatum. Finally, we examined the impact of treatment of the donor tissue with ciliary neurotrophic factor (CNTF) on graft survival. CNTF has previously been shown to protect striatal neurons against excitotoxic insults both in vitro and in vivo, but it did not improve striatal graft survival when added to the cell suspension prior to implantation.

Animals↗
PubMed2004

The effect of hyperbaric oxygen therapy on composite graft survival.

Auricular composite grafts are a useful reconstructive option, particularly for nasal reconstruction. This study evaluates the effect of hyperbaric oxygen (HBO) therapy on auricular composite graft survival in rabbits. Circular chondrocutaneous composite grafts of 0.5, 1, or 2 cm in diameter were resected from the ears of rabbits. The grafts were sutured back into position. Half the rabbits in each group received HBO postoperatively, consisting of 90 minutes at 2.4 atm. Rabbits received 7 treatments in 5 days. Control rabbits did not receive HBO. On day 21 the percentage area of graft survival was calculated from gross and histologic examination. Two-centimeter grafts treated with HBO (n = 8) had a mean graft survival rate of 85.8 +/- 15.7% compared with a survival rate of 51.31 +/- 38.5% for the control group (n = 8; P = 0.0478). There was no such benefit in smaller grafts. HBO could prove clinically useful for larger composite grafts.

Animals↗