Relative Risk Of Graft Loss Research Articles

Is Body Mass Index a Significant Independent Risk Factor for Graft Failure and Patient Death in the Modern Immunosuppressive Era?

ObjectivesPrevious studies have shown that kidney transplant recipients with a high body mass index (BMI) have inferior graft and patient outcomes compared to patients with a lower BMI. We hypothesized that there would be secular improvements in outcomes among high BMI recipients. We used data from the United Network for Organ Sharing (UNOS) to determine whether obesity affects patient and graft outcomes following kidney transplantation in the modern immunosuppressive era. MethodsThe study sample consisted of 69,749 recipients from 1987 to 1999 and 197,986 recipients from 2000 to 2016. BMI values were categorized into 11 tiers: below 18 kg/m2, from 18 to 36 kg/m2 at 2 kg/m2-unit increments, and above 36 kg/m2. We created multivariate models to evaluate the independent effect of BMI on graft and patient outcomes, adjusting for factors known to affect graft success and patient survival. ResultsOverall graft and patient survival has improved for all BMI categories. Cox regression modeling hazard ratios showed that the relative risk for graft loss, patient death, and patient death with a functioning graft in the modern immunosuppressive era (2000 to 2016) has significantly decreased compared to the earlier era (1987 to 1999), especially for living kidney transplant recipients. ConclusionsThe relative risk of graft failure and patient death with increasing BMI has appreciably decreased in the modern immunosuppressive era, especially for living donor transplant recipients. Withholding transplantation from patients with higher BMIs may no longer be justifiable on grounds of worse clinical outcomes.

Cost-effectiveness and value of information analysis of a low-friction environment following skin graft in patients with burn injury

BackgroundPatients with burn injuries may receive a skin graft to achieve healing in a timely manner. However, in around 7% of cases, the skin graft is lost (fails to attach to the wound site) and a re-grafting procedure is necessary. It has been hypothesised that low-friction (smooth, more slippery) bedding may reduce the risk of skin-graft loss. A before and after feasibility study comparing low-friction with standard bedding in skin-grafted patients was conducted in order to collect proof of concept data. The resulting relative risk on the primary outcome (number of patients with skin graft failure) for the non-randomised study provided no evidence of effect but had a large standard error. The aim of this study is to see if an appropriately powered randomised control trial would be worthwhile.MethodsA probabilistic decision-analytic model was constructed to compare low-friction bedding to standard care in a population of burn patients who have undergone skin grafting. Results from the before and after study were used as model inputs. The sensitivity of results to bias in the relative risk of graft loss was conducted. Low-friction bedding is considered optimal if expected incremental net benefit (INB) is positive. Uncertainty is assessed using cost-effectiveness acceptability curves. Expected Value of Perfect Partial Information (EVPPI) provides an upper bound for the potential net health benefits of new research for given model input.ResultsAt a willingness to pay threshold of £20,000 per QALY, INB = £151 (95% Credible Interval (CrI) −142 to 814), marginally favouring low-friction bedding but with high uncertainty (probability of being cost-effective 70.5%). Expected value of perfect information (EVPI) per patient was £20.29, which results in a population EVPI of £174,765 over a 10-year lifetime for the technology (based on 1000 patients per year who would benefit from the intervention). The parameter contributing most to the uncertainty was the inpatient care cost, i.e. information that could be obtained from the audit of practice and without an expensive trial. These findings were robust to a wide-range of assumptions about the potential bias due to the observational nature of the comparative evidence.ConclusionsOur study results suggest that an RCT (randomised controlled trial) is unlikely to be worthwhile, but there may be value in a study to estimate the re-graft rates and associated costs in this population.

SAT-092 IS BODY MASS INDEX A SIGNIFICANT INDEPENDENT RISK FACTOR FOR GRAFT FAILURE AND PATIENT DEATH IN THE MODERN IMMUNOSUPPRESSION ERA?

Previous studies have shown that kidney transplant recipients with a high body mass index (BMI) have an inferior graft and patient outcomes compared to patients with a lower BMI. We used data from the United Network for Organ Sharing (UNOS) to determine whether obesity affects patient and graft outcomes following kidney transplantation in the modern immunosuppressive era. The study sample consisted of 69,749 recipients from 1987-1999 and 197,986 recipients from 2000-2016. We created multivariate models to evaluate the independent effect of BMI on graft and patient outcomes, adjusting for factors known to affect graft success and patient survival. Cox regression modeling hazard ratios showed that the relative risk for graft loss, patient death and patient death with a functioning graft in the modern immunosuppressive era (2000-2016) has significantly decreased compared to the earlier era (1987-1999) especially for living kidney transplant recipients. Figure 1. The distribution of pretransplantation BMI according to era. Figure 2. Cox proportional hazards model for graft loss and patient death with graft function according to period by categorized BMI in living kidney transplantation.(A: Relative risk for graft loss in year 1987-1999, B: Relative risk for graft loss in year 2000-2016, C: Relative risk for patient death with graft function in year 1987-1999, D: Relative risk for patient death with graft function in year 2000-2016) The relative risk of graft failure and patient death with increasing BMI has appreciably decreased in the modern immunosuppressive era, especially for living donor transplant recipients. Withholding transplantation from patients with higher BMIs may no longer be justifiable on grounds of worse clinical outcomes.

The dynamics of pre-existing anti-HLA antibodies and the results of kidney transplantation

Aim. To analyze the relationship between the peak panel-reactive antibodies (peak-PRA), the value at the time of transplantation (Tx-PRA) and the results of kidney transplantation.Materials and methods. The study included 287 patients from the waiting list with anti-HLA antibodies of I and/or II classes. 142 patients underwent transplantation of a cadaveric kidney. All patients received standard immunosuppression: a calcineurin inhibitor, mycophenolate and steroids. Desensitization in the preoperative period was carried out in 11 patients. Screening and identification of antibodies was performed using multiplex technology on Luminex platform.Results. The median PRA was 47% (interquartile range – 29%; 65%). Depending on the dynamics of PRA, we identified several groups of patients: stable PRA (83 patients), increasing (77 patients) or decreasing value (96 patients), or variable dynamics (31 patients). The change in PRA was accompanied by a change in the mean fluorescence intensity (r = 0.787, r2 = 0.59, p < 0.0001). In the univariate analysis, each 5% of peak-PRA and Tx-PRA increased the relative risk (RR) of humoral graft rejection (1.09 (95%CI 1.06; 1.17), p < 0.001; 1.17 (95%CI 1.09; 1.26), p < 0.001 respectively), and ΔPRA decreased a RR (0.932 (95% CI 0.861; 0.967), p = 0.009). In multivariate analysis (adjusted for sex and age of recipient, duration of dialysis, number of HLA mismatches), we observed a similar scenario: peak-PRA 1.14 (95% CI 1.07; 1.19), p < 0.001; Tx-PRA 1.13 (95% CI 1.09; 1.22), p < 0.001; ΔPRA 0.949 (95% CI 0.871; 0.981), p = 0.017. In the univariate analysis increases in peak- PRA and Tx-PRA increased aRR of graft loss (1.1 (95% CI 1.05; 1.14), p < 0.001; 1.09 (95% CI 1.05; 1.15), p < 0.001 respectively), and increase in ΔPRA decreased RR (0.952 (95% CI 0.891; 0.97), p = 0.011). In the adjusted multivariate model, Tx-PRA did not increasea RR of graft loss (1.04 (95% CI, 0.95; 1.1), p = 0.098), while peak-PRA and ΔPRA remained significant factors (1.1 (95% CI, 1.17; 1.24), p < 0.001; 0.931 (95% CI, 0.855; 0.954), p = 0.007, respectively). Conclusion. In the selection donor-recipient pair it is necessary to take into account the spectrum of antibodies at the point of peak values of PRA. A decrease in PRA may hide antibodies that have a specificity to donor antigens or on certain epitope.

Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies: a systematic review.

Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain. We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available. Thirty-six studies involving 10535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95% CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R2 = 1.00, P < 0.001) and region of study conduction (R2 = 0.50, P = 0.005) modified associations between dnDSAs and outcomes. dnDSAs are associated with increased risks of adverse graft and patient outcomes after kidney transplantation, but estimation uncertainty of the augmented risks exist due to limitations such as heterogeneity within the existing literature. Therapeutic interventions targeted to eliminate or prevent these antibodies evaluated in randomized controlled trials are needed to establish whether dnDSAs are causal to transplantation outcomes.

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

Clinical outcomes associated with induction regimens among retransplant kidney recipients in the United States.

Numerous studies have evaluated outcomes and risk factors associated with induction protocols among kidney transplant recipients. However, few studies have evaluated outcomes in the subset of retransplant recipients who often have unique immunologic condition and risk profile and represent an increasing proportion of transplant patients in the United States. We evaluated the association of common induction treatments (alemtuzumab, thymoglobulin, interleukin-2 receptor blockers, and no induction) given at transplantation with clinical outcomes among adult recipients retransplant between 2003 and 2011 using national Scientific Registry of Transplant Recipients data (n = 14,336). We used a propensity score analysis to minimize potential selection biases for allocation of treatment. In adjusted models, there were no significant differences between induction groups for outcomes of delayed graft function, 1-year acute rejection, 1-year BK virus or patient death. Acute rejection before hospital discharge was lowest among patients treated with thymoglobulin and alemtuzumab. The no induction group had the highest average 1-year estimated glomerular filtration rate (62 mL/min/1.73 kg/m(2)) and lowest incidence of any malignancies within 1 year (1.0%). Hospitalizations after transplantation were highest among patients treated with thymoglobulin (42% at 1 year). Recipients with alemtuzumab had the highest relative risk for graft loss (adjusted hazard ratio, 1.19; 95% confidence interval, 1.01-1.40, relative to patients treated with thymoglobulin). There is moderate variation in clinical outcomes associated with induction treatment among retransplant kidney recipients in the United States, including higher graft loss rates among recipients treated with alemtuzumab but similar patient survival between all regimens.

Influence of donor specific HLA antibodies detected by Luminex in kidney graft survival: A multivariate analysis

Some studies have demonstrated the clinical relevance of a positive virtual crossmatch in graft survival; nevertheless, other donor and recipient variables influence the outcome of the transplant. The aim of this study was to investigate the relevance of a positive virtual crossmatch in the graft survival performing a multivariate analysis including other pretransplant variables. A total of 879 deceased kidney transplantations were included. Univariate and multivariate analyses were performed using Cox regression model. After performing the multivariate analysis, a positive virtual crossmatch against class I (adjusted HR 6.613; 95% CI 3.222-13.573), class II (adjusted HR 2.419; 95% CI 1.170-5.002) and class I+II (adjusted HR 5.717; 95% CI 1.925-16.975) detected by single antigen Luminex was the variable conferring the greatest relative risk of graft loss. A positive virtual crossmatch predicts a worse kidney graft survival even after correction by other variables and therefore, transplantation of patients with positive virtual crossmatches should be avoided.

The Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation

We examined the frequency and clinical impact of acute rejection (AR) in contemporary U.S. kidney transplantation. Data for Medicare-insured kidney transplant recipients in 2000 to 2007 (n=48,179) were drawn from the United States Renal Data System. AR events were ascertained from Organ Procurement and Transplantation Network reports. AR was subclassified as antibody (Ab)-treated AR or other management (non-Ab-treated AR). Associations of AR with subsequent all-cause graft loss were estimated with time-varying Cox regression. Covariates included recipient, donor, and transplant factors in the United Network for Organ Sharing Kidney Allocation Review Committee survival model. The frequencies of non-Ab-treated AR per 100 graft-years at risk among standard criteria donor recipients over the first 6, 12, 24, and 36 months after transplantation were 9.93, 8.43, 5.71, and 4.70, respectively. Non-Ab-treated AR was consistently more than twice as common as Ab-treated AR by risk period and donor type. Development of Ab-treated AR predicted a greater risk of graft loss than non-Ab-treated AR. The relative risk for graft loss from Ab-treated AR continuously increased with later timing of AR after transplantation, whereas risk associated with non-Ab-treated AR peaked for events reported in months 13 to 24 after kidney transplantation. Regardless of the diagnosis time, the relative risk of graft loss was higher in the first 89 days after a given AR report compared with 90 days and beyond. AR events recognized later after transplantation have more serious graft loss implications, especially within the first 89 days after AR reporting. This observation may reflect reduced intensity of monitoring, delays in diagnosis, or clinicopathologic features of late AR.

Underutilization of A2 ABO incompatible kidney transplantation.

ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant. Death-censored graft survival was compared between A recipients and O, B, and AB recipients of an A2 allograft with multivariate Cox regression models utilizing data from the United Network of Organ Sharing (UNOS) between 1997 and 2007. Eighty-five percent of A2 kidneys were transplanted into ABO compatible recipients vs. 15% into ABO incompatible recipients. Rates of A2 incompatible kidney transplants did not increase over the study period (14.8% to 14.6%). Mean wait time for A2→O kidneys was 337 vs. 684 d for O→O and for A2→B kidneys, 542 vs. 734 d for B→B. Adjusted relative risk of graft loss at five-yr was similar between O, B, and AB recipients compared to A recipients of an A2 allograft, corresponding to a five-yr graft survival of 84%, 86.2%, 86.1%, and 86.1%, respectively. A2 incompatible kidney transplantation is underutilized. Graft outcomes are similar among A2 compatible and incompatible recipients. Shorter waiting time and improved access might be achieved if A2 kidneys are considered in all blood groups.

HLA-A, -B, and -DR Zero-Mismatched Kidneys Shipped to the University of Wisconsin, Madison, 1993–2006: Superior Graft Survival Despite Longer Preservation Time

To determine the impact at a single center of the United Network for Organ Sharing-mandated sharing program for human leukocyte antigen (HLA)-A/-B/-DR 0-mismatched (0MM) kidneys, we analyzed the results of 264 kidney transplants from 0MM distant donors between 1993 and 2006, with a follow-up through January 31, 2007. We compared these results with that of concurrent kidneys transplanted from HLA more than 0MM local donors and with shipped more than 0MM kidneys from "payback" donors. Despite a significantly longer preservation time, we found an 11% increase in 8-year graft survival (63% vs. 52%; P<0.003) of 0MM shipped versus locally procured, >0MM donor kidneys. Graft survival of 0MM shipped kidneys at 8 years was significantly better in nonsensitized (<20% panel reactive antibodies; 68% vs. 55%; P<0.0005) but not in sensitized (>or=20% panel reactive antibodies) recipients, who showed an early (2 years) but short-lived benefit. The benefit of receiving a HLA-A, -B, and -DR 0MM shipped kidney remained strong and statistically significant (0.71 relative risk of graft loss vs. local; P<0.02) when adjusted for 22 potentially confounding variables in a Cox proportional hazards analysis. The recent change in United Network for Organ Sharing policy restricting mandated sharing of 0MM kidneys to sensitized and pediatric recipients will give greater flexibility to the local organ procurement organization in allocating organs. However, the survival benefit to nonsensitized patients is real and long lasting and will be lost.

Alemtuzumab Versus Interleukin-2 Receptor Antibodies Induction in Living Donor Kidney Transplantation

Alemtuzumab use has been increasing in kidney transplantation. We aimed to compare posttransplantation outcomes between alemtuzumab and interleukin-2 receptor antibodies (IL-2RA) in living donor kidney transplant recipients in the United States. Organ Procurement Transplant Network/United Network of Organ Sharing data, as of August 2007, were used to identify all living donor kidney transplants performed in adults in the United States from 2003 to 2006 where induction therapy with alemtuzumab or IL-2RA (daclizumab or basiliximab) was used. Primary outcomes included incidence of acute rejection, graft survival, and patient survival. One thousand nine hundred thirteen recipients received alemtuzumab and 7011 received IL-2RA. There were few significant differences in baseline characteristics. The incidence of acute rejection at discharge was lower in the alemtuzumab group, when compared with that in the IL-2RA group (0.8% vs. 4.4%, respectively, P<0.001), but it was similar by 1 year posttransplant (9.8% vs. 11%, respectively). After adjusting for confounding factors, those in alemtuzumab group had a higher adjusted relative risk of graft loss (hazard ratios 1.23, 95% CI 1.03-1.48) in 4 years. Patient survival was comparable between the study groups. A higher rate of acute rejection and graft failure was seen in the recipients who used triple regimen (calcineurin-mycophenolate-steroid) in association with alemtuzumab. The incidence of acute rejection at discharge was lower with alemtuzumab but was comparable with IL-2RA up to 1 year posttransplant. There was no difference in patient survival, but the risk of graft loss among patients who received alemtuzumab was higher compared with those who received IL-2RA induction.

The role of positive flow cytometry crossmatch in late renal allograft loss

Many studies relating flow cytometery crossmatch (FCXM) results to kidney transplant outcomes have examined risk in the first 3 to 12 months. We used Organ Procurement and Transplant Network registry data for 66,594 kidney transplants from 1995 to 2007 to investigate associations of T-cell positive (T +) and T-cell negative/B-cell positive (T −B +) FCXM with graft failure risk early (years 0–1) and late (years >1–5) after transplant. Compared with transplants with T-cell negative/B-cell negative (T −B −) FCXM, living-donor transplants performed after T + FCXM had significantly higher adjusted, relative risks of both early (adjusted hazards ratio [aHR] 1.71, p < 0.0001) and late (aHR 1.36, p = 0.017) graft loss. T −B + FCXM was associated with approximately 40% higher relative risk of graft loss in the late period only. Patterns were similar for deceased-donor transplants. The risks of positive FCXM persist beyond the peritransplant period for years after transplant. Damage by memory effector cells may explain the long-term risks associated with positive FCXM.

Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr </=1.5, 1.6-2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6-2.0 and >2.0 mg/dL, compared to </=1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5-7.6) and 1.6-2.0 mg/dL (AOR 2.7; CI 2.5-2.9) relative to sCr </=1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

Outcomes of Kidney Transplantation From Older Living Donors to Older Recipients

More than half the newly wait-listed patients for kidney transplantation in 2005 were older than 50 years, and 13% were older than 65 years. As waiting times for a deceased donor kidney increase, these older candidates are disadvantaged by rapidly deteriorating health, often resulting in death or removal from the wait list before transplantation. An observational cohort study was conducted using data from the Organ Procurement Transplant Network/United Network for Organ Sharing. All adult kidney-only transplantations performed in recipients 60 years and older from 1996 to 2005 were included. The recipient cohort was stratified into 4 groups based on donor source: older living donor (OLD: living donor age > 55 years), younger living donor (YLD: living donor age </= 55 years), standard criteria deceased donor (SCD), and expanded criteria deceased donor (ECD). Early posttransplantation outcomes, graft survival, patient survival, renal function 1 year posttransplantation, and relative risk of graft loss and patient death were compared. Of 23,754 kidney transplantations performed in recipients 60 years and older, 7,006 were living donor transplantations (1,133 were > 55 years [OLD] and 5,873 were <or= 55 years [YLD]), 12,197 from SCDs, and 4,551 from ECDs. Early posttransplantation outcomes were best in YLD transplantations, followed by SCD and OLD transplantations. OLD transplantations were associated with inferior 3-year graft survival rates (85.7%), but similar 3-year patient survival rates (88.4%) compared with YLD (3-year graft survival, 83.4%; patient survival, 87.4%) and had superior graft survival compared with all deceased donor options. Compared with OLD transplantations, ECD transplantations were associated with a greater risk of graft loss (hazard ratio, 2.36; 95% confidence interval, 1.18 to 4.74). Observational retrospective studies using registry data are subject to inherent limitations, including the possibility of selection bias. With superior graft and patient survival in recipients of transplants from OLDs compared with SCDs and ECDs, OLDs may be an important option for elderly transplantation candidates and should be considered for older patients with a willing and suitable older donor.

Patient and Graft Outcomes from Deceased Kidney Donors Age 70 Years and Older: An Analysis of the Organ Procurement Transplant Network/United Network of Organ Sharing Database

The organ shortage has resulted in more use of older deceased donor kidneys. Data are limited on the impact of donor aged 70 years and older on transplant outcomes. We examined patient and graft outcomes of renal transplant from expanded criteria donors (ECDs) aged 70 years and older, using the Organ Procurement Transplant Network/United Network of Organ Sharing database. We identified 601 deceased donor transplants from donors older than 70 years from 2000 to 2005. The follow-up time was until May 2007. Allograft and patient survival were compared between recipients of transplants from older ECDs (age > or =70) and younger ECDs (age 50-69). The relative risk of graft loss and patient death were determined using multivariate models. The adjusted relative risks of overall graft loss (hazards ratio [HR] 1.37; 95% confidence interval [CI] 1.19-1.58), death-censored graft loss (HR 1.32; 95% CI 1.09-1.61), and patient death (HR 1.37; 95% CI 1.15-1.64) were greater among recipients of transplants from older ECD kidneys. The relative risk of patient death was lower when older ECD kidneys were transplanted into recipients older than 60 compared with recipients aged 41 to 60. In contrast, the relative risk of death-censored graft loss was not increased when older ECD kidneys were transplanted into recipients older than 60. Transplants from older ECD kidneys are associated with a higher risk of graft loss and patient death. The risk was highest when older ECD kidneys were transplanted into recipients younger than 60 years.

Blacks as Donors for Transplantation: Suboptimal Outcomes Overcome by Transplantation Into Other Minorities

Background In 1977, Opelz et al (Transplant Proc 9:137, 1977) introduced research that identified ethnic disparities in the relative risk of graft loss when African American donors or recipients were targeted. Current research from the Organ Procurement and Transplantation Network (OPTN) reveals a continuation of these trends. While 1-year graft survival rates for a kidney are 92.1% for Caucasians, 94.1% for Asians, and 92.9% for Latinos, the comparative rate is 88.9% for African Americans. This study extends research on health disparities by examining relative differences in graft and patient survival rates when the organ donors are African American. A number of factors have been introduced as possible determinants of disparate outcomes by ethnicity in terms of graft survival rates. This descriptive study was designed to test the hypothesis: There are no differences in the relative risks associated with graft survival rates and mortality based upon differences in the ethnicity of the donors. Materials and Methods Data were obtained from the OPTN/United Network for Organ Sharing (UNOS) Registry from April 1, 1994 to December 31, 2000. A total of 118,769 transplants were analyzed, including 77,689 living and deceased donor kidney transplants, 26,124 deceased donor liver transplants, and 14,956 deceased donor heart transplants. A multivariate Cox regression model was used to determine the relative risk of graft loss and cardiac transplant mortality for different ethnicities when the organ donors were African American. Results The study found that the relative risk of kidney graft loss was 21.3% ( P < .01) higher between African American donors and Caucasian recipients than between Caucasian donors and other recipients. With liver transplants, the use of an African American donor increased the risk of graft loss by 21.5% ( P < .001). When African American donors gave kidneys and livers to other African Americans, the relative risks of kidney graft loss were 50.9% higher for a kidney ( P < .001) and 36.6% higher for a liver ( P < .001) if both the donors and recipients were African American. The relative risk of mortality was 51.3% higher ( P < .001) when African American hearts were transplanted into other African Americans. No significant differences existed in terms of the relative risk of cardiac mortality ( P < .29) when African American hearts were transplanted into Caucasian recipients. When African American donors provided kidneys and livers to Latinos and Asians, the relative risk of graft loss fell below the rates for Caucasian donors and recipients. However, the differences were not statistically significant. Conclusions Our data have identified a pressing need to conduct clinical and prospective research that can isolate the causes of these suboptimal outcomes. This is particularly important since the number of African American organ donors has escalated as a result of recent health outreach and education efforts.

Conversion to sirolimus for chronic allograft dysfunction: long-term results confirm predictive value of proteinuria

The aim was to evaluate long-term graft survival and function after conversion to sirolimus (SRL) for chronic calcineurin inhibitor (CNI) toxicity and the predictive value of baseline proteinuria. This is a follow-up conversion study of 59 renal transplant patients with deteriorating graft function and histologic signs of CNI toxicity. Previously, baseline proteinuria <800 mg/day was identified as a short-term predictor for successful conversion. Follow-up was 5.3 +/- 0.8 (3.7-6.8) years. Patient survival was 88%, graft survival 38%. Creatinine clearance at the last follow-up was 33.7 +/- 14 ml/min, proteinuria 826 +/- 860mg/day. Baseline proteinuria <800 mg/day was associated with better graft survival. In a cox analysis including proteinuria >800 mg, glomerular filtration rate, age at conversion, chronic Banff score at conversion and time after transplantation at conversion, higher proteinuria was associated with a relative risk of graft loss of 3.98. Prognosis of chronic allograft dysfunction is poor. However, conversion to SRL remains an option for patients with low baseline proteinuria, which can slow down deterioration of graft function during a follow-up period of up to 5 years.

Alemtuzumab Induction in Deceased Donor Kidney Transplantation

The use of alemtuzumab for induction therapy in kidney transplantation has been increasing. Herein is a report of graft outcomes associated with alemtuzumab induction from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. A total of 14,362 deceased donor kidney transplants from 2003 to 2004 received no induction (n=4,364), antithymocyte globulin (ATG; n=4,930), interleukin-2 receptor antagonists (IL-2RA; n=4,378), or alemtuzumab (n=690). Acute rejection within the initial hospitalization, 6 months, and 1 year; graft survival; and rejection-free survival were examined. Graft and rejection-free survival of alemtuzumab recipients maintained with tacrolimus (FK) or cyclosporine (CSA), mycophenolate mofetil (MMF), and steroids versus no calcineurin inhibitors (CNI), MMF, and steroids were compared. Alemtuzumab recipients had less acute rejection during the initial hospitalization (2.3%) than no induction, ATG, and IL-2RA (7.6%, 3.4%, and 4.8%, respectively; P<0.001). There was increased acute rejection at 6 months and 1 year with alemtuzumab (14.5% and 19.2%) compared to no induction (12.7% and 14.8%, P<0.001), ATG (8.2% and 10.2%, P<0.001), and IL-2RA (11.1% and 13.0%, P<0.001) with no difference in adjusted relative risk for graft loss. Alemtuzumab recipients receiving FK or CSA, MMF, and steroids had increased graft (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.007) and rejection-free survival (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.006) over 24 months compared to no CNI, MMF, and steroids. Despite reduced early rejection, acute rejection rates at 6 months and 1 year with alemtuzumab induction exceeded other forms of induction therapy. Maintenance with CNI-based immunosuppression may improve graft and rejection-free survival compared to CNI-free regimens among alemtuzumab recipients.

Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation.

Hepatitis C virus (HCV) infection is common in kidney transplantation and is known to affect long-term patient and graft survival, as is time in renal-replacement therapy (RRT). The aim of this study was to investigate HCV in relation to time in RRT and its impact on outcome after transplantation. A follow-up cohort study using Kaplan-Meier analysis and Cox proportional hazards model was performed in 545 kidney and 26 kidney-pancreas transplant recipients receiving transplants between 1989 and 1997, with last follow-up on December 31, 2002. HCV status at transplantation and time in RRT were analyzed. Time in RRT was significantly longer (P<0.0001), and previous transplantations were more common (P=0.04) in the HCV-positive group. HCV significantly reduced patient (P=0.0012) and graft survival (P=0.0003) after transplantation. Adjustment for age, sex, diabetes, previous transplantations, type of transplant, and time in RRT resulted in a relative risk (RR) for death of 2.23, 1.92, and 1.07 for HCV, diabetes, and age, respectively. The RR for graft loss was 1.96 and 1.03 for HCV and age. Sex, previous transplants, and time in RRT did not affect HCV as an independent risk factor for patient or graft survival. The leading cause of death was cardiovascular disease in both groups. HCV was, in our series, more important than time in RRT for patient death and graft loss posttransplant. Successful pretransplant antiviral therapy could be more beneficial for HCV-infected patients rather than early transplantation for long-term outcome, but this needs to be studied prospectively.