Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

BACKGROUND: Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. METHODS: Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. RESULTS: Five-year actuarial graft survival for living donor transplant with SCr >1.5 and 1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. CONCLUSION: Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.     

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.     

肾移植后急性排斥反应发生相关术前因素分析

目的探讨影响肾移植术后发生急性排斥反应的相关术前因素,为预防移植肾急性排斥反应的发生提供临床依据。方法回顾性分析2002年1月～2008年12月在浙江大学医学院附属第一医院肾脏病中心首次接受同种异体尸体肾移植受者1316例资料,记录基线资料及术后急性排斥反应发生情况;按群体反应性抗体(PRA)水平10%和≥10%将受者分为PRA阴性组和致敏组;以2005年10月1日为界分为回顾性HLA配型组和前瞻性HLA配型组。统计分析各基线资料对术后急性排斥反应发生的影响以及不同组间急性排斥反应发生率的差异。结果手术时受者年龄、术前PRA水平、热缺血时间、HLA错配数对术后急性排斥反应的发生有显著影响。致敏组术后6个月内急性排斥反应发生率(58.8%比17.9%,P0.001)以及6个月内组织病理学检查证实急性排斥反应发生率(29.4%比11.9%,P=0.028)均显著高于PRA阴性组。采用前瞻性HLA配型后受者HLA错配数减少,且术后6个月内急性排斥反应发生率也降低(20.9%比15.5%,P=0.012)。结论术前检测受者的PRA水平从而准确评估其致敏状态,尽可能选择良好的HLA配型谱可减少移植肾术后急性排斥反应的发生。     

Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study

BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group. METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified. RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients. CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.     

Comparison of outcomes after delayed graft function: sirolimus-based versus other calcineurin-inhibitor sparing induction immunosuppression regimens

BACKGROUND: Sirolimus (SRL) may increase the incidence of or prolong delayed graft function (DGF) after cadaveric renal transplantation. This study compares transplant outcomes of SRL-based induction immunosuppression (IS) with other calcineurin-inhibitor (CNI) sparing regimens in the DGF setting. METHODS: Adult cadaveric renal-transplant recipients who received transplants between January 1, 1997 and June 30, 2001 and experienced DGF (n=132) were divided into three groups by induction IS: A, depleting antibody (n=41); B, SRL (n=49); and C, neither (n=42). All recipients also received steroids and mycophenolate mofetil with delayed initiation of CNIs when good renal function returned. Patient survival, graft survival, and time to rejection within 1 year of transplantation were assessed by Kaplan-Meier analysis. One-year graft function was compared using Kruskal-Wallis and Fisher's exact tests. RESULTS: The SRL group had longer DGF duration (P=0.01). The three groups had comparable patient (P=0.27) and graft survival (P=0.69), but the depleting antibody group experienced less rejection (P=0.004). There were no clinically significant differences in 1-year graft function. CONCLUSIONS: In our analysis of a large and modern cohort of adult cadaveric transplant recipients with DGF, induction immunosuppression with a depleting antibody preparation reduced rejection, whereas SRL prolonged DGF duration. All three CNI-sparing induction IS regimens resulted in comparable patient survival, graft survival, and graft function.     

Hospitalized psychoses after renal transplantation in the United States: incidence,risk factors,and prognosis

Although it is recommended that renal transplant (RT) candidates routinely undergo screening for mental health-related conditions, national statistics for psychoses after RT have not been reported. This is a historical cohort study of 39,628 renal transplant recipients in the United States Renal Data System between July 1, 1994, and June 30, 1998, and followed until December 31, 1999. Adjusted hazard ratios (AHR) for time to hospitalization for both a primary and secondary discharge diagnosis of psychoses (ICD-9 codes 290.x-299.x) after RT and mortality/graft loss after psychosis were assessed by Cox Regression. In addition, rates of psychosis were compared with 178,986 patients with Medicare as their primary payer who started chronic dialysis from April 1, 1995, to June 29, 1999. The incidence of psychoses was 7.5/1000 person-years (PY) after RT compared with 7.2/1000 PY for all patients on chronic dialysis and 9.6/1000 PY for dialysis patients aged 65 yr or younger. Among RT recipients, graft loss (AHR, 2.97; 95% CI, 2.19 to 4.02), allograft rejection, and cadaveric donation were independently associated with psychosis, which was associated with an increased risk of both death (AHR, 2.09; 95% CI, 1.71 to 2.56; P < 0.001) and graft loss (AHR, 1.79; 95% CI, 1.15 to 2.78; P = 0.01). Graft loss due to noncompliance was significantly more common after psychosis (9.0% versus 3.7% in patients not hospitalized for psychosis; P < 0.001). The incidence of hospitalized psychosis was not substantially higher after RT compared with chronic dialysis patients. Psychoses were independently associated with increased risk of death and graft loss after renal transplantation, possibly mediated through medical non-adherence.     

Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.     

Delayed graft function: risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study

BACKGROUND: Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. RESULTS: Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. CONCLUSIONS: Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.     

Does delayed kidney graft function increase the risk of chronic rejection?

Abstract  The impact of delayed graft function (DGF) on later renal graft loss due to chronic rejection was studied in a single center using uniform protocol for organ procure merit and post transplant patient care. DGF function was observed in 34 % of 829 consecutive first cadaveric renal transplants in adults and in 47 % of 169 retransplantations (P < 0.05). There were no significant differences in graft survival between groups with early graft function (EGF) and DGF, either in first transplantations or retransplantations. The half-life in EGF and DGF groups of first transplants was 12.3 years and 10.5 years, respectively, and of retransplantants was 8.0 years and 6.5 years, respectively. DGF was divided in three subgroups according to the day of onset. If graft function started during the first or second week after transplantation there were no significant differences in long-term graft survival rates compared with EGF. Only in re-transplants, if graft function started later than 2 weeks postoperatively, were long-term graft survival rates significantly lower when compared with EGF and the difference persisted if other causes of graft loss except chronic rejection were censored.     

Calcium levels as a risk factor for delayed graft function

BACKGROUND: Delayed graft function (DGF) occurs in up to 50% of renal transplants. Hypercalcemia and hyperparathyroidism are associated with impaired renal function. Little is known on the effects of serum calcium levels on DGF. This issue was addressed in the current study. METHODS: Patients receiving a cadaveric renal transplant between 1986 and 1996 were studied. Data on calcium metabolism and histologic characteristics of nephrocalcinosis, acute tubular necrosis (ATN), and acute rejection in biopsies taken within the first week were related to the occurrence of DGF. RESULTS: The incidence of DGF in a cohort of 585 cadaveric transplants was 31%. DGF correlated independently with serum calcium levels (odds ratio [OR] 1.14 [95% confidence interval (CI) 1.04-1.26] per 0.1 mmol/L). The use of calcium channel blockers before transplantation protected against DGF (OR 0.5 [95% CI 0.29- 0.87]). In this selected group, we found an association with histologic signs of ATN and DGF. However, most of the biopsies also had features of acute rejection or nephrocalcinosis. Nephrocalcinosis was found in 12 of 71 biopsies and was not associated with serum calcium levels or the occurrence of DGF. CONCLUSIONS: In this study, serum calcium levels were independently associated with DGF. This could not be explained by the presence of microscopic nephrocalcinosis. Therefore, DGF is attributed to high intracellular calcium levels. Because calcium supplementation and vitamin D analogues are commonly used in dialysis practice, hypercalcemia influences long-term graft outcome by its effect on DGF. The pretransplant use of calcium channel blockers has a protective effect on the occurrence of DGF.     

高度致敏肾移植患者的围术期处理

目的 探讨高度致敏肾移植患者的围手术期处理.方法 对22例高度致敏肾移植患者术前组织配型及预处理,术后抗排异方案以及肾功恢复情况进行研究.结果 17例患者术前经血浆置换3～8次后群体反应性抗体(PRA)降至30%以下,5例患者术前PRA仍大于50%.术后发生超急性排斥反应(HAR)1例(9.9%),抗排异反应未能逆转,予以切除移植肾;急性排斥反应(AR)8例(36.3%),经甲强龙+ATG(ALG)冲击治疗后6例肾功恢复正常,2例转为肾功能延迟恢复(DGF);术后DGF5例(22.7%),予以血液透析+低剂量抗排异药物维持,肾功均恢复正常.结论 避开相应抗体进行良好的组织配型,是高度致敏患者肾移植成功的关键;术前行血浆置换降低高度致敏患者PRA,使用ATG或ALG可降低手术风险,提高排斥反应逆转率.     

Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft

BACKGROUND: Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). METHODS: We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. RESULTS: By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001). CONCLUSION: Longer CIT induces a humorally more immunogenic kidney.     

Cadaveric renal transplantation with cyclosporine in patients more than 60 years of age

Advanced age has been a relative contraindication to kidney transplantation because of the likelihood of increased morbidity and mortality in the geriatric population. However, the introduction of cyclosporine has improved renal allograft survival rates dramatically, and higher-risk patients are now being successfully transplanted. With the introduction of cyclosporine in 1983, we have performed 36 cadaveric renal transplants in 34 recipients 60 years of age or older, including 34 primary and 2 retransplants. Most of the patients (88%) were on dialysis prior to transplantation and 29% had ASCVD. Three-year actuarial patient and allograft survival are 91% and 74%, respectively. Surgical complications were infrequent, and postoperative rejection episodes were less frequent than in younger patients but were more likely to lead to graft loss. Medical complications, especially infection, were common after transplantation but easily managed. Cadaveric renal transplantation with cyclosporine immunosuppression is a safe and effective therapeutic modality that is no longer contraindicated in elderly patients.     

Reduced graft function (with or without dialysis) vs immediate graft function--a comparison of long-term renal allograft survival.

BACKGROUND: Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre. METHODS: The renal allograft function of 972 first cadaveric transplants performed between 1990 and 2001 in the Republic of Ireland was examined. The DGF and IGF were defined by a creatinine reduction ratio (CRR) between time 0 of transplantation and day 7 post-transplantation of <70 and >70%, respectively. Recipients with reduced graft function (DGF) not requiring dialysis were defined as slow graft function (SGF) patients. The serum creatinine at 3 months, 6 months, 1, 2 and 5 years after transplantation was compared between these groups of recipients. The graft survival rates at 1, 3 and 5 years and the graft half-life for DGF, SGF and IGF recipients were also assessed. RESULTS: Of the 972 renal transplant recipients, DGF was seen in 102 (10.5%) patients, SGF in 202 (20.8%) recipients and IGF in 668 (68.7%) patients. Serum creatinine levels were significantly different between the three groups at 3 and 6 months, 1, 2 and 5 years. Graft survival at 5 years for the DGF patients was 48.5%, 60.5% for SGF recipients and 75% for IGF patients with graft half-life of 4.9, 8.7 and 10.5 years, respectively. CONCLUSION: This study has shown that the CRR at day 7 correlates with renal function up to 5 years post-transplantation and with long-term graft survival. We have also demonstrated that amongst patients with reduced graft function after transplantation, two groups with significantly different outcomes exist.     

Machine perfusion of donor kidneys may reduce graft rejection

Recent evidence suggests that hypothermic machine perfusion of donor kidneys reduces delayed graft function (DGF). This study addresses the effect of machine perfusion (MP) on allograft rejection in the United States. We assembled a retrospective cohort of patients undergoing kidney‐alone transplants in the UNOS database from June 30, 2004 to May 31, 2017. DGF was defined as dialysis requirement in the first week post‐transplant; graft rejection was defined at 6 months and 1 year. Multivariable logistic regression adjusted for recipient and donor factors evaluated the effect of MP on DGF and graft rejection. Records for 79 300 kidney transplants meeting inclusion criteria were abstracted, 42% of which underwent MP. MP kidneys came from older donors, were more likely to have been obtained following donation after cardiac death, and had longer cold ischemic times. Rates of DGF and rejection were similar between MP and static storage kidneys. Following adjustment, recipients of MP kidneys were less likely to experience rejection at 1 year (OR 0.91 [95% CI 0.86‐0.97] P = .002), but not at 6 months post‐transplantation (OR 0.94 [0.88‐1.02] P = .07). This effect persisted following adjustment for cold ischemic time. This study adds to the accumulating evidence demonstrating improved outcomes following MP of kidneys. We encourage protocolized consideration of MP for kidney grafts.     

Evaluation of flowcytometric crossmatching in renal allograft recipients.

Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients.     

Predictors and outcomes of delayed graft function after living‐donor kidney transplantation

Delayed graft function (DGF) following deceased donor kidney transplantation is associated with inferior outcomes. Delayed graft function following living‐donor kidney transplantation is less common, but its impact on graft survival unknown. We therefore sought to determine risk factors for DGF following living‐donor kidney transplantation and DGF's effect on living‐donor kidney graft survival. We analyzed living‐donor kidney transplants performed between 2000 and 2014 in the UNOS dataset. A total of 64 024 living‐donor kidney transplant recipients were identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants were independent predictors of DGF in living‐donor kidney transplants. Five‐year graft survival among living‐donor kidney transplant recipients with DGF was significantly lower compared with graft survival in those without DGF (65% and 85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft failure (hazard ratio = 2.3, 95% confidence interval: 2.1–2.6; P < 0.001). DGF after living‐donor kidney transplantation is associated with inferior allograft outcomes. Minimizing modifiable risk factors may improve outcomes in living‐donor kidney transplantation.     

Role of donor age and acute rejection episodes on long-term graft survival in cadaveric kidney transplantations

Cadaveric donors can provide an effective solution to the problem of organ shortage, and many factors that may affect the functioning and survival of cadaveric kidneys have been studied. We aimed to clarify the impact of donor age and acute rejection episodes on long-term graft and patient survival in patients receiving cadaveric renal transplants. We retrospectively evaluated the long-term outcomes of 207 patients who had received cadaveric renal transplants between 1985 and 2004. Mean recipient age, HLA mismatch, mean donor age, delayed graft function (DGF), mean cold ischemia time, acute rejection episodes in the first 6 months after transplantation, and 1-, 3-, and 5-year graft survivals were evaluated. Two study groups were created according to donor age: group 1 (n = 126) was composed of patients receiving kidneys from donors younger than 50 years, and group 2 (n = 81) was composed of patients receiving kidneys from donors 50 years of age or older. Mean recipient age, HLA mismatch, and mean cold ischemia time between groups were not different. The DGF rate in group 1 was 40% (n = 50) and in group 2 was 46% (n = 37) (P > .05). The 1-, 3-, and 5-year survival rates of patients without acute rejection within the first 6 months after transplantation in group 1 (58/126; 46%) versus those in group 2 (46/81; 57%) were 95% versus 90%, 65% versus 60%, and 40% versus 35%, respectively (P > .05). The 1-, 3-, and 5-year graft survival rates of patients with acute rejection within the first 6 months in group 1 (n = 68) versus those in group 2 (n = 35) were 93% versus 89%, 71% versus 55%, and 44% versus 28%, respectively (P = .005). There was no significant difference in 1-, 3-, and 5-year survival rates between patients with DGF in both groups. Acute rejection episodes within the first 6 months after cadaveric transplantation, especially in patients receiving kidneys from donors older than 50 years, were shown to affect 5-year survival of the kidney graft. However, cadaver age alone had no negative effect on 5-year graft survival rates. Cadaveric donors older than 50 years may be a solution to the organ shortage in the treatment of end-stage renal disease.     

Induction With Basiliximab in Renal Transplantation

Introduction

The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals.

Objective

We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals.

Methods

We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2).

Results

We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals.

Conclusion

In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.     

Impact of the delayed graft function in hypersensitized kidney transplant patients

AIM: The aim was to study the incidence, impact, and association of pretransplantation anti-HLA antibodies and delayed graft function (DGF) on the outcome of cadaver kidney transplants independent of the immunosuppressive therapy. METHODS: Data from 1325 cadaver donor kidneys (February 1975 to December 2002) included the variables of current and peak anti-HLA antibodies, presence of DGF, acute rejection (AR) episodes, patient survival, and graft half-life. RESULTS: DGF (need for dialysis in the first week posttransplantation) ranged between 15% and 40% with a mean of 30% in last 5 years. Eighty-five percent of the candidates on the waiting list for kidney transplants displayed <25% panel reactive antibody (PRA) at transplantation with 4.6% between 26% and 50%, 7.7% between 51% and 75%, and 1.5% >75%. Among the patients who developed DGF, 47% displayed AR compared an incidence of 30% among patients without DGF (P=.0026). The patients displaying >50% PRA (either current or maximum) showed a worse graft survival compared with patients with <50% PRA (log rank, P=.0000). DGF reduced graft survival (P=.04), the difference appearing in the early phase after transplantation. The best outcome was observed in the no DGF-no AR group (half-life, 11.6 years) and the worst results were in the hypersensitized patient groups: peak and current PRA >50% (half-lives of 2.4 and 2.2 years). A multivariate analysis showed that the presence of peak or current PRA >50% is the most important risk factor for graft loss. CONCLUSION: Sensitization is the key factor in graft outcome. Presensitization increases the risk of DGF and DGF increases the incidence of AR and both together produce the worst graft survivals.