Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry.

BACKGROUND. The importance of HLA histocompatibility typing to the outcome of transplantation of cadaveric kidneys has been controversial. Four years ago, a prospective trial began in all U.S. transplantation centers to determine whether the results of transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to waiting patients undergoing dialysis when there was a match at the HLA-A, B, and DR loci. METHODS. A total of 1386 cadaveric kidneys were shipped from 108 organ centers to 198 transplantation centers and distributed among HLA-matched recipients, 1004 of whom were receiving a first transplant and 382 of whom were receiving a subsequent transplant. Graft survival in these recipients was compared with that in 22,188 recipients of first transplants and 3950 recipients of subsequent transplants whose HLA antigens differed from those of the donor. RESULTS. The rate of graft survival at one year in recipients of HLA-matched first transplants was 88 percent, as compared with 79 percent in the recipients of mismatched grafts (P less than 0.001). The estimated half-life of the kidney after the first year was 17.3 years for matched grafts, as compared with 7.8 years for mismatched grafts (P = 0.003). Among paired kidneys from 470 donors, one-year graft survival was 87 percent in the recipients of matched first grafts, as compared with 80 percent in the recipients of the contralateral kidneys, who did not have HLA matches with the donors. In donors and recipients matched for the more highly defined split Class I and Class II HLA antigens, the rate of graft survival after one year was as high as 90 percent. CONCLUSIONS. The collaborative renal-transplantation program for HLA matching of donors and recipients yielded an increased rate of one-year graft survival and an estimated half-life for matched grafts twice that for mismatched grafts. An increased role for HLA matching in kidney allocation is therefore indicated.     

HLA compatibility and organ transplant survival. Collaborative Transplant Study

The influence of HLA compatibility on organ transplant survival was analyzed in more than 150,000 recipients transplanted from 1987 to 1997 at transplant centers participating in the Collaborative Transplant Study. A statistically highly significant effect of HLA matching on graft and patient survival rates was found in the analysis of kidney transplants (P < 0.0001). Ten years after transplantation, the graft survival rate of first cadaver kidney transplants with a complete mismatch (6 HLA-A+B+DR mismatches) was 17% lower than that of grafts with no mismatch. During the first post-transplant year, the class II HLA-DR locus had a stronger impact than the class I HLA-A and HLA-B loci. During subsequent years, however, the influence on graft survival of the three loci was found to be equivalent and additive. For optimal graft outcome, compatibility at all three HLA loci is, therefore, desirable. The excellent correlation of HLA matching observed in recipients of cadaver kidneys with very short ischemic preservation (0-6 hours) or recipients of kidneys from living unrelated donors contradicts reports that short ischemia can eliminate the influence of matching. Although HLA has a significant effect on graft outcome regardless of the state of presensitization, the matching effect is potentiated in patients with highly reactive preformed lymphocytotoxic antibodies. Among first cadaver transplant recipients with an antibody reactivity against > 50% of the test panel, the difference in graft survival at 5 years between patients with 0 or 6 mismatches reached 30%. A collaborative project, in which molecular DNA typing methods were employed, showed that the correction of serological HLA typing errors by more accurate DNA typing results in a significantly improved HLA matching effect. Moreover, matching for the class II locus HLA-DP, a locus that can be typed reliably only by DNA methods, showed a significant effect in cadaver kidney retransplants, especially in the presence of preformed lymphocytotoxic antibodies. The analysis of heart transplants showed a highly significant impact of HLA compatibility on graft outcome (P < 0.0001). This result is of particular interest because donor hearts are not allocated according to the HLA match. A biasing influence of donor organ allocation (i.e. a preferential allocation of good matches to good risk recipients) can, therefore, be excluded. In liver transplantation, neither matching for HLA class I nor HLA class II could be shown to influence transplant outcome.     

活体亲属供肾肾移植的临床分析

目的　总结分析活体亲属供肾肾移植的手术和治疗经验 ,探讨其临床效果 .方法　回顾性分析 33例活体亲属供肾肾移植的临床资料 ,包括手术方法和创新、免疫抑制药物的用药方案及临床效果 .结果　本组全部切取左肾 ,经腹手术 ,手术顺利 ,移植肾在开放血液循环后 1～ 10分钟内分泌尿液 .供体肾功能在 1周内恢复正常 ,未出现严重并发症 .受者仅 2例出现急性排斥反应 .全部受者至今存活 ,肾功能良好 .结论　活体亲属供肾 ,移植效果明显优于尸体供肾肾移植 .排斥反应发生率低 ,恢复顺利     

Long-term outcome of kidney transplantation in adult recipients with focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. FSGS recurrence after renal transplantation has a potentially detrimental course leading to the loss of renal function. In order to establish FSGS recurrence rates and evaluate the course of the disease on living-related-donor renal transplantation in ethnic Korean adults (> or = 18 years), we reviewed our experiences of 27 kidney transplantations with FSGS over the last 15 years. Of the 27 renal allografts, 13 were found to have recurrent FSGS by graft biopsy. In comparison with background data upon patients with and without recurrence of FSGS, the donor age of patients with recurrent FSGS was significantly higher than that of those without recurrence (median, 39 years vs 26, p < 0.05). In terms of, age at transplantation, length of dialysis period, and mode of dialysis no differences were found between recurrent and nonrecurrent cases. The graft survival rate of recipients from a kidney donor of age less than 40 years was significantly higher than that of recipients from a kidney donor of age more than 40 years, at 5 and 10 years, respectively (87% vs 33%, 41% vs 0%, p < 0.05). The association between clinical variables and recurrence was assessed by multiple logistic regression analysis, and donor age was found to be a risk factor of FSGS recurrence (p<0.05). Variables such as HLA-mismatch numbers and immunosuppression were not found to be associated. In conclusion, the recurrence rate of FSGS in adult recipients with FSGS was 48% and patients that received kidney from an older donor appear to be at higher risk of developing recurrence. The use of a renal graft from a younger donor is considered advisable for adult recipients with FSGS.     

配偶供肾移植后微嵌合体发生与急性排斥反应

背景：微嵌合作为移植物与受者之间的双相细胞移动的标志,在移植免疫耐受中的作用日益受到重视。 目的：探讨夫妻生活与嵌合体的发生,与肾移植后急性排斥反应及其他相关性的研究。 方法：将接受肾脏移植的女性受者(有过生育史的女性除外)分为丈夫活体供肾组、无关男性尸体供肾组,并设立接受妻子活体供肾的对照组。STR方法检测女性受者体内男性供者来源的Y染色体反映微嵌合体的存在,与急性排斥反应发生的关系,并比较配偶间供肾效果的差异。 结果与结论：尽管配偶间供肾移植存在供者年龄偏大以及人类白细胞抗原错配率较高的因素,但与接受无关男性尸肾移植的女性受者相比,接受丈夫活体供肾移植的女性更易检测出微嵌合体,而且肾移植后恢复情况好,急性排斥反应发生率低。而与接受妻子供肾的丈夫相比,接受丈夫供肾的妻子肾移植效果好。说明夫妻间长期相处导致女性接受丈夫体液的机会多,由此产生免疫耐受对于肾移植后人/肾的相容性好,急性排斥反应小。     

Improved graft survival after renal transplantation in the United States, 1988 to 1996

BACKGROUND: The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known. METHODS: We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation. RESULTS: From 1988 to 1996, the one-year survival rate for grafts from living donors increased from 88.8 to 93.9 percent, and the rate for cadaveric grafts increased from 75.7 to 87.7 percent. The half-life for grafts from living donors increased steadily from 12.7 to 21.6 years, and that for cadaveric grafts increased from 7.9 to 13.8 years. After censoring of data for patients who died with functioning grafts, the half-life for grafts from living donors increased from 16.9 years to 35.9 years, and that for cadaveric grafts increased from 11.0 years to 19.5 years. The average yearly reduction in the relative hazard of graft failure after one year was 4.2 percent for all recipients (P<0.001), 0.4 percent for those who had acute rejection (P=0.57), and 6.3 percent for those who did not have acute rejection (P<0.001). CONCLUSIONS: Since 1988, there has been a substantial increase in short-term and long-term survival of kidney grafts from both living and cadaveric donors.     

The benefit of exchanging donor kidneys among transplant centers

Whether kidneys from cadaver donors should be exchanged among transplant centers is controversial. We analyzed the effect of matching for HLA-B and HLA-DR antigens on graft survival in patients treated with cyclosporine. The results in 9369 recipients of kidneys obtained and transplanted in the same center were compared with those in 5553 recipients of kidneys shipped from one center to another. In both patient subgroups, the association of HLA matching with graft survival was statistically significant (P less than 0.0001). Moreover, well-matched exchanged kidneys survived better than poorly matched locally transplanted kidneys. Among patients receiving their first cadaver transplant, graft survival at one year was 13 percentage points higher (P less than 0.0001) in exchanged kidneys without mismatches than in local kidneys with four mismatches. Among patients receiving their second transplant, graft survival was 21 percentage points higher (P less than 0.001). Kidney preservation for up to 48 hours did not affect graft survival significantly. Transplantation of poorly matched local kidneys preserved with a short period of cold ischemia (less than 24 hours) had significantly lower rates of success than did transplantation of well-matched exchanged kidneys with a longer period of cold ischemia (up to 48 hours) (P less than 0.0001). Our data indicate that the exchange of cadaver kidneys among transplant centers to obtain grafts with better HLA matching can improve the success rate of renal transplantation.     

DNA damage in kidney transplant patients. Role of organ origin

Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. Environ. Mol. Mutagen. 58:712–718, 2017. © 2017 Wiley Periodicals, Inc.     

Renal transplantation between HLA identical siblings. Comparison with transplants from HLA semi-identical related donors.

We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.     

新疆地区活体肾移植178例随访

背景：新疆的特殊之处在于是国内少数民族与汉族混杂聚集地,新疆地区目前尚无少数民族与汉族间活体肾移植有种族差异的明确报道。 目的：比较新疆地区少数民族与汉族间活体肾移植的种族差异。 方法：回顾性分析新疆地区1999/2010行活体肾移植受者的临床资料,并对移植前、后一般临床资料,以及移植后少数民族与汉族间移植肾存活率进行比较分析,将可能影响移植肾存活率的各种因素进行单因素分析。 结果与结论：纳入随访资料完善者178例,其中少数民族131例,汉族47例。汉族组受者的移植肾存活率较少数民族组患者稍高,但差异无显著性意义。对可能影响长期移植肾生存的因素进行Cox单因素分析,显示急性排斥反应对移植肾生存有明显影响。提示新疆地区不同民族间接受同种民族活体肾移植的短中期移植肾存活率差异无显著性意义,急性排斥反应为影响移植肾存活的重要因素。     

Failure of BCL-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function

SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation.     

Pre- and postoperative care of living relative patients for renal transplantation

Between 1966 and 1989, 54 kidney transplants were performed at our institute. We present our experience about pre- and postoperative care of the patients for renal transplantation. 1) Donors 1) Pre- and postoperative function of the kidneys and urinary tract must be evaluated carefully. Renal transplantation can be done successfully if preoperative renal function is good even if the donor is older than 60 years old. 2) Preoperative evaluation of the donor renal artery is necessary. Four kidneys with renal artery anomalies and one kidney with renal artery aneurysm were used for renal transplantation uneventfully after they were repaired. 2) Recipients 1) We had 4 recipients who demonstrated abnormality of the urinary tract. They all received successful renal transplantation after appropriate urological management before renal transplantation. 2) Imaging diagnostic technique is useful when graft function is deteriorated. Acute rejection can be diagnosed more objectively using renal scintiscan and echogram. They are also useful for early detection of postoperative urological complications. In this paper, the diagnostic strategy using various imaging techniques was outlined.     

Fibrin thrombi in deceased donor kidneys: Prevalence and influence on graft function and graft survival in transplanted patients

Fibrin thrombi (FT) are occasionally found in the pre‐implantation biopsy of kidneys from deceased donors. The aim of this study was to monitor the prevalence and answer the question whether FT has any impact on future graft function in a Danish patient cohort. We looked for FT in all donor kidney biopsies taken at the time of renal transplantation in a Danish transplantation unit during a 10‐year period. Every recipient transplanted with a FT donor kidney (n = 15) were matched with up to five control recipients (n = 69), and graft function and graft survival were assessed. FT was present in 3% of the transplanted donor kidneys. Graft function was reduced in the FT group 6 months after transplantation (median estimated glomerular filtration rate (eGFR): 29 mL/min vs 46 mL/min; p = 0.017), but at 12 months, an apparent difference did not reach statistical significance. More patients were on dialysis in the FT group after 12 months compared with the control group (27% vs 6%; p = 0.049). In conclusion, FT in donor kidney biopsies at time of transplantation is a risk factor for the development of reduced renal function during the first year of transplantation.     

Effect of the use or nonuse of long-term dialysis on the subsequent survival of renal transplants from living donors

BACKGROUND: The effect on allograft survival of the transplantation of kidneys from living donors without the previous initiation of long-term dialysis is controversial. METHODS: Using data from the U.S. Renal Data System, we performed a retrospective cohort study of 8481 patients who were or who were not treated by long-term dialysis before receiving a kidney transplant from a living donor. The relative rate of allograft failure for patients who received a transplant without previously undergoing long-term dialysis, as compared with patients who underwent long-term dialysis before transplantation, was assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including the transplantation center and median household income. The association between the receipt of a kidney transplant from a living donor without previous dialysis ("preemptive transplantation") and the risk of biopsy-confirmed acute rejection within six months after transplantation was evaluated by conditional logistic-regression analysis, with adjustment for the transplantation center. RESULTS: Transplantation of a kidney from a living donor without previous long-term dialysis was associated with a 52 percent reduction in the risk of allograft failure during the first year after transplantation (rate ratio, 0.48; P=0.002), an 82 percent reduction during the second year (rate ratio, 0.18; P=0.001), and an 86 percent reduction during subsequent years (rate ratio, 0.14; P=0.001), as compared with transplantation after dialysis. The reduction in the rate of allograft failure during the first year was attenuated when adjustment was made for the timing of acute rejection within the first year (rate ratio, 0.69; 95 percent confidence interval, 0.44 to 1.10; P=0.10). Increasing duration of dialysis was associated with increasing odds of rejection within six months after transplantation (P=0.001). CONCLUSIONS: Preemptive transplantation of kidneys from living donors without the previous initiation of dialysis is associated with longer allograft survival than transplantation performed after the initiation of dialysis.     

Living kidney donation--selection criteria, preparation and follow-up

Since a dialysis patient in Austria still waits on average more than two years for a renal transplant, the question of a transplant from a living donor is very interesting. We differentiate between related and non-related living donors, who are chosen on the basis of medical criteria and emotional ties. Austria's first three kidney transplants from related donors were performed in 1967. Since then a total of 317 kidneys from genetically related donors have been transplanted until December 31, 2000. Transplants from non-related living donors were performed once in 1982, once in 1990 and since 1995 in a steadily increasing number each year, until they reached 47 by December 31, 2000. The United Network for Organ Sharing calculated the ten-year survival rate for functional grafts for a four-year period (1995-1998) in more than 30,000 renal transplant recipients from HLA-identical twins, non-related living donors, parent and cadaver donors. As anticipated, this study demonstrates that HLA-identical twins (n = 1,581) have the most functional grafts (81%), followed by non-related donor-recipients (n = 1,704) at 67% despite their often poor HLA match, parent-child transplants (n = 2,428) at 62% and cadaver renal grafts (n = 26,178) at 50%. Therefore, medical aspects as well as influences from the psychosocial environment would appear to be decisive for transplantation success. Thus, when choosing from several possible living donors it is absolutely justifiable to choose a donor with a poorer HLA match but good emotional ties. Such a choice requires strict selection criteria, and surgical preparation and follow-up demand the greatest care. While the criteria given in this paper are meant to be guidelines to help in deciding for a liver donor, they certainly do not rule out a different approach following critical reflection and participation by the affected parties, namely donor and recipient, as well as their advisors, nephrologist, transplant surgeon and psychotherapist. At the same time we need to make every effort to further intensify the use of cadaver kidneys. Only in this way can we ensure optimal implementation of all the resources available to us for supplying renal grafts to dialysis patients.     

Renal transplantation in pre-school children

This short report describes the outcome of 13 renal transplants in 11 children under 5 years of age. Nine (82%) of the 11 recipients are alive; 2 children died with functioning grafts. Approximately 50% of grafts are functioning at 5 years post transplantation. Children with congenital kidney malformations can be successfully managed to transplantation.     

Severely atypical changes in renal epithelium in biopsy and graft nephrectomy specimens in two cases of cadaver renal transplantation

Severely atypical metaplastic and dysplastic changes were noted in the lining epithelium of collecting tubules and pelvis of the graft kidneys in two cases of cadaver renal transplants on immunosuppressive treatment with azathioprine and prednisolone. These changes were observed in case 1 in a needle biopsy and a nephrectomy specimen, 3 and 3.5 years after transplantation respectively. In a second case, the patient received two cadaver grafts, and both transplants showed similar changes 2 years after transplantation. The risk of malignant disease in kidney transplant recipients is now well recognized. The implications of the severe dysplastic changes noted in these two cases are discussed.     

The influence of HLA-DR match on the outcome of cadaver renal transplantation in Stockholm during 1977–1980

The influence of HLA-DR match grade on graft and on patient survival was analyzed in 124 recipients of cadaver kidneys who were treated in Stockholm between January 1977 and September 1980. The material consisted of 72 males and 52 females, with a mean age of 49 years. There were 34 re-transplantations. Eighteen of the recipients had diabetes. Sera against the HLA-DR antigens 1–4, 7 and DRw8 were available throughout. During recent years, DR5 sera were also used. The case material was analyzed as to the number of DR antigens shared or to the number of DR incompatibilities between the donor and the recipient. A significant improvement in graft survival rate was found for transplants sharing one HLA—DR antigen as compared with those sharing none. As far as incompatibilities are concerned, a significant difference was found between transplants with no incompatibilities and those with two. The HLA—A, B incompatibilities were evenly distributed throughout the various groups and thus should not have introduced a bias in the interpretation of the influence of HLA-DR match. We conclude that HLA-DR matching has a very beneficial effect on the graft survival rate and we shall in future try to obtain the best possible match when selecting recipients for cadaver kidney transplantation.     

Racial differences in the survival of cadaveric renal allografts. Overriding effects of HLA matching and socioeconomic factors.

BACKGROUND. The long-term survival of cadaveric renal allografts is lower in black recipients than in white recipients, although the one-year graft survival is similar in these racial groups. We sought to determine what factors account for this disparity. METHODS. We studied 100 consecutive recipients of primary cadaveric renal allografts (57 were black and 43 white) at least 1 year after transplantation (mean, 40 months); all had received identical immunosuppressive therapy. We evaluated differences in the cause and duration of end-stage renal disease, the number of pretransplantation transfusions, age, matching for HLA-A, B, and DR antigens, race of the donor, insurance coverage, and compliance to assess their effect on graft survival in both groups. RESULTS. Allograft survival after one year was significantly lower in black than in white patients (P = 0.025). According to univariate analysis, only the recipient's age at transplantation, the number of mismatches for HLA antigens, the type of insurance coverage, the source of referral for transplantation, and the degree of compliance correlated significantly with the rate of graft survival. The frequency of all variables that reduced graft survival was higher among the blacks. According to proportional-hazards analysis, the only factors contributing to a lower rate of graft survival were age of less than 30 years at transplantation (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.6), mismatches for all six HLA antigens as compared with three or fewer mismatches (relative risk, 5.6; 95 percent confidence interval, 3.3 to 9.6), and coverage by Medicaid or Medicare (relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.2). Race had no additional effect. Noncompliance was more frequent among blacks (16 percent vs. 2 percent) and could substitute for insurance status in the model. CONCLUSIONS. When immunosuppression is equivalent in black and white transplant recipients, apparently race-related differences in the long-term survival of renal cadaveric allografts appear to be related to other factors that affect graft survival unfavorably, notably poor HLA matching and unfavorable socioeconomic factors.