Relative Risk Of Graft Failure Research Articles

Assessment of donor quality and risk of graft failure after liver transplantation: The ID2EAL score

Accurate assessment of donor quality at the time of organ offer for liver transplantation candidates may be inadequately captured by the donor risk index (DRI). We sought to develop and validate a novel objective and simple model to assess donor risk using donor level variables available at the time of organ offer. We utilized national data from candidates undergoing primary LT (2013-2019) and assessed the prediction of graft failure 1year after LT. The final components were donor Insulin-dependent diabetes mellitus, Donor type (DCD or DBD), cause of Death=CVA, serum creatinine, Age, height, and weight (length). The ID2 EAL score had better discrimination than DRI using bootstrap corrected concordant index over time, especially in the current era. We explored donor-recipient matching. Relative risk of graft failure ranged from 1.15 to 3.5 based on relevant donor-recipient matching by the ID2 EAL score. As an example, for certain recipients, a young DCD donor offer was preferable to an older DBD with relevant comorbidities. The ID2 EAL score may serve as an important tool for patient discussion about donor risk and decisions regarding offer acceptance. In addition, the score may be preferable to succinctly capture donor risk in future organ allocation that considers continuous distribution (www.iddealscore.com).

The Algorithm for Using Transit-time Flow Measurement and High-resolution Epicardial Ultrasound for Intraoperative Grafts Assessment during Coronary Artery Bypass Surgery.

Aim To develop an algorithm for using ultrasonic flowmetry (USF) and epicardial ultrasonic scanning (EpiUSS) for intraoperative assessment of anatomic and functional viability of conduits.Material and methods For viability assessment of 460 coronary grafts in 150 patients who were operated at the Bakulev National Medical Research Center for Cardiovascular Surgery (2018-2021 г.), markers of graft failure were analyzed using the USF and EpiUSS data confirmed by results of graft angiography. According to RОС analysis, the Qmean and PI values indicative of the graft failure were determined. A CHAID decision tree was developed for assessing the prognostic significance of the analyzed parameters. Based on this prognostic model, an algorithm was developed for intraoperative diagnosis of anatomic and functional graft viability during coronary bypass surgery.Results The Qmean ≤20.5 ml/min values were associated with an increased relative risk (RR) of detecting graft failure (RR, 8.2; 95 % confidence interval, CI, 4.4-15.2). The developed model shows a high accuracy of predicting the graft failure (AUC = 0.906±0.03). The RR of graft failure at PI ≥2.65 was 3.3 (95 % CI, 2.17-5.08). The prognostic model for PI (AUC = 0.745±0.042) was sufficiently accurate with respect of possible graft failure. Nodes of high and low risk for graft failure were determined in the developed decision tree. The obtained model was characterized by high sensitivity and specificity (100 and 84.3 %, respectively).Conclusion The combined use of USF and EpiUSS allows a highly accurate assessment of both morphological and functional characteristics of graft flow. The developed algorithm for the intraoperative diagnosis of anatomic and functional graft viability can be recommended for clinical use.

Isolated Osteochondral Autograft Versus Allograft Transplantation for the Treatment of Symptomatic Cartilage Lesions of the Knee: A Systematic Review and Meta-analysis

Background: Focal cartilage lesions of the knee remain a difficult entity to treat. Current treatment options include arthroscopic debridement, microfracture, autograft or allograft osteochondral transplantation, and cell-based therapies such as autologous chondrocyte transplantation. Osteochondral transplantation techniques restore the normal topography of the condyles and provide mature hyaline cartilage in a single-stage procedure. However, clinical outcomes comparing autograft versus allograft techniques are scarce. Purpose: To perform a comprehensive systematic review and meta-analysis of high-quality studies to evaluate the results of osteochondral autograft and allograft transplantation for the treatment of symptomatic cartilage defects of the knee. Study Design: Systematic review and meta-analysis; Level of evidence, 2. Methods: A comprehensive search of the literature was conducted using various databases. Inclusion criteria were level 1 or 2 original studies, studies with patients reporting knee cartilage injuries and chondral defects, mean follow-up ≥2 years, and studies focusing on osteochondral transplant techniques. Exclusion criteria were studies with nonknee chondral defects, studies reporting clinical outcomes of osteochondral autograft or allograft combined with other procedures, animal studies, cadaveric studies, non–English language studies, case reports, and reviews or editorials. Primary outcomes included patient-reported outcomes and failure rates associated with both techniques, and factors such as lesion size, age, sex, and the number of plugs transplanted were assessed. Metaregression using a mixed-effects model was utilized for meta-analyses. Results: The search resulted in 20 included studies with 364 cases of osteochondral autograft and 272 cases of osteochondral allograft. Mean postoperative survival was 88.2% in the osteochondral autograft cohort as compared with 87.2% in the osteochondral allograft cohort at 5.4 and 5.2 years, respectively (P = .6605). Patient-reported outcomes improved by an average of 65.1% and 81.1% after osteochondral autograft and allograft, respectively (P = .0001). However, meta-analysis revealed no significant difference in patient-reported outcome percentage change between osteochondral autograft and allograft (P = .97) and a coefficient of 0.033 (95% CI, –1.91 to 1.98). Meta-analysis of the relative risk of graft failure after osteochondral autograft versus allograft showed no significant differences (P = .66) and a coefficient of 0.114 (95% CI, –0.46 to 0.69). Furthermore, the regression did not find other predictors (mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location) that may have significantly affected patient-reported outcome percentage change or postoperative failure between osteochondral autograft versus allograft. Conclusion: Osteochondral autograft and allograft result in favorable patient-reported outcomes and graft survival rates at medium-term follow-up. While predictors for outcomes such as mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location did not affect the comparison of the 2 cohorts, proper patient selection for either procedure remains paramount to the success and potentially long-term viability of the graft.

Systematic Assessment of Safety Threshold for Donor Age in Cadaveric Liver Transplantation.

Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature.Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model.Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors <43 years old were not associated with age-related risks (P > 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P < 0.05).Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.

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.

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.

KIR Ligand Incompatibility in the Host Versus Graft Direction Predicts Graft Failure and Dominant Graft in Cord Blood Transplantation but Not in Haploidentical Transplantation

Donor-derived natural killer (NK) cell alloreactivity has been shown to improve clinical outcomes following allogeneic stem cell transplant (HSCT). Host versus graft (HvG) directed NK cell alloreactivity can also occur. Several epitopes of HLA-B and HLA-C are ligands for inhibitory killer immunoglobulin-like receptors (KIRs) that regulate NK cell cytotoxicity. These KIR ligands (KIR-L) may be surrogates of NK cell alloreactivity in the HLA-mismatched setting. To determine the impact of donor/recipient KIR-L mismatch (KIR-L-MM) direction on engraftment, we examined cord blood (CBT) and haploidentical (Haplo) HSCT performed at our institution between 2011 and 2018. We computed KIR-L and direction of KIR-L-MM for recipient/ donor pairs using the KIR ligand calculator (https://www.ebi.ac.uk/ipd/kir/ligand.html). Summary data and the relative risk of graft failure were analyzed. In the CBT cohort (N=70), there were KIR-L mismatches (KIR-L-MM) in the HvG and GvH direction in 32 and 31 recipient-cord blood unit pairs respectively. There were no KIR-L-MM in 26 transplants while seven had KIR-L-MM in both GvH and HvG directions. Overall, 16 CBT failed to engraft (23%). There was an increased risk of graft failure in recipients of HvG KIR-L-MM transplants (R.R 2.15; p=0.063) with this trend most significant when the mismatch was in HLA-C ligand (R.R 2.46; p=0.027); Figure 1. Out of 8 double CBTs where one cord unit had HvG KIR-L-MM, the non-mismatched unit fully engrafted in 7 cases (87.5%). In 6 double CBTs where there was KIR-L-MM from one cord unit in the GvH and the GvG (graft versus other graft) direction, 4 (67%) of such units became the dominant graft. Of 8 double CBTs in which both cord units had KIR-L-MM in the HvG direction there was graft failure in 3 (37.5%). Time to neutrophil engraftment and lymphocyte recovery when engraftment occurred was not significantly impacted by KIR-L-MM. In the Haplo cohort (N=26), all of the 5 graft failures (19%) were KIR-L mismatched only in the GvH direction (R.R 9.53; p=0.114). There were 9 HvG KIR-L-MM transplants and they all engrafted. Fourteen transplant pairs in this cohort had KIR-L-MM in the GvH direction; 2 pairs had both HvG and GvH KIR-L-MM while 3 pairs did not have any KIR-L-MM. Time to neutrophil engraftment was not impacted by GvH or HvG KIR-L-MM. This study suggests an increased likelihood of graft failure in CBT when HvG KIR-L-MM exists. There is also a trend in favor of engrafting the GvH/GvG KIR-L-MM unit in double CBT. These factors should be considered when selecting cord units for CBT. A similar graft failure effect of HvG KIR-L-MM is not seen in this small Haplo cohort; on the contrary the data suggests GvH directed KIR-L-MM associates with graft failure. This association merits exploration in a larger database.

Evaluating the economic implications of non-adherence and antibody-mediated rejection in renal transplant recipients: the role of once-daily tacrolimus in the UK

Background and aims:While short-term kidney graft survival has gradually improved over time, improvements in long-term graft survival have been more modest. One key clinical factor limiting improved longer-term outcomes is antibody-mediated rejection (AbMR), the incidence of which appears to be higher in patients who are non-adherent to immunosuppressants. Recent data show that adherence can be improved by reducing pill burden. The aim of the present study was to model the incidence and economic consequences of graft loss and AbMR in patients taking once- vs twice-daily tacrolimus in the UK.Methods:A combined decision tree and Markov model was developed to estimate the incidence of graft failure, AbMR and mortality in renal transplant recipients taking once- vs twice-daily tacrolimus. Underlying rates of graft failure and mortality were derived from UK-specific sources. Proportions of patients adherent to once- vs twice-daily tacrolimus were taken from a recent randomized clinical trial and relative risks of graft failure and AbMR were taken from a prospective, multi-center analysis of 315 patients. Cost data were taken from the British National Formulary and National Health Service reference costs and reported in 2014 pounds sterling.Results:Modeling results showed that improved adherence would be associated with reduced incidence of AbMR and graft failure in renal transplant recipients. Based on improvements in adherence resulting from switching from twice-daily to once-daily tacrolimus, the modeling analysis projected cost savings of GBP 4862 per patient over 5 years with Advagraf relative to Prograf, on absolute costs of GBP 40,974 and GBP 45,836, respectively.Conclusions:Using Advagraf in place of Prograf in renal transplant recipients was predicted to be associated with lower pharmacy, dialysis and AbMR treatment costs, with the reduction in AbMR and dialysis costs being driven by improved adherence to the Advagraf regimen and consequent reductions in graft failure and onset of AbMR.

Decision making in liver transplantation-Limited application of the liver donor risk index

The liver donor risk index (LDRI), originally developed in 2006 by Feng et al. and since modified, is a method of evaluating liver grafts from deceased donors through the determination of the relative risk of graft failure after transplantation. Online and paper surveys about attitudes and practices regarding decision making in liver transplantation and the role of the LDRI were sent to liver transplant physicians. One hundred forty-seven of 401 eligible respondents (37%) returned partial or complete surveys. The majority of the respondents were male (116/134 or 87%) and practiced in academic medical centers (128/138 or 93%). Transplant coordinators initially contacted the candidate with an offer in 81% of the programs. Eighty-eight of 143 respondents (62%) reported that they were very familiar with the LDRI, but the vast majority (114/137 or 83%) rarely or never discussed the concept of the LDRI with their patients. A majority of the respondents (96/132 or 73%) believed that the LDRI does not adequately describe a liver's relative risk of graft failure and that there are factors making the LDRI potentially misleading (122/138 or 88%). Nevertheless, 60 of 130 respondents (46%) believed that the LDRI would increase/improve shared decision making. The LDRI has not been widely adopted because of concerns that (1) it does not accurately reflect posttransplant survival, (2) it excludes relevant donor and recipient factors, and (3) it is too complicated for candidates to grasp. There is a need to improve it or to develop other decision-making tools to help promote shared decision making. There is also great diversity in how liver offers are made to ambulatory candidates and in how transplant programs address a candidate's refusal. Research is needed to determine evidence-based best practice.

Budget impact of switching from an immediate-release to a prolonged-release formulation of tacrolimus in renal transplant recipients in the UK based on differences in adherence.

Background and aimsAdvagraf is a once-daily prolonged-release formulation of tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release formulation of tacroli-mus, in biopsy-proven acute rejection, graft survival and patient survival in renal transplant recipients. Advagraf is associated with improved adherence compared with Prograf, which may ultimately improve long-term outcomes. The present study assessed the budget impact of switching patients from Prograf to Advagraf in the UK.Materials and methodsA budget-impact model was constructed based on published data on acute rejection, graft failure, and mortality in the UK setting. Patients were assumed to convert from Prograf to Advagraf on a 1:1 milligram:milligram basis. In a study comparing the adherence rates between once-daily versus twice-daily formulations of tacrolimus, the proportion of patients taking the prescribed number of daily doses was 88.2% in Advagraf patients and 78.8% in Prograf patients. The model applied a relative risk of graft failure of 3.47 to nonadherent patients based on data from a 2004 meta-analysis (based on graft-failure rates of 1.3%–40.0% in adherent patients, compared with 6.1%–100% in nonadherent patients). Cost data were taken from the March 2013 British National Formulary and 2012–2013 National Health Service tariff information. The analysis was performed over a 5-year time horizon and future costs were not discounted, in line with International Society for Pharmacoeconomics and Outcomes Research guidelines.ResultsOver a 5-year time horizon, the mean cost per patient (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection) was £29,328 (standard deviation [SD] £2,844) for Advagraf versus £33,061 (SD £3,178) for Prograf. The total cost saving of £3,733 (SD £530) was driven primarily by reduced dialysis costs arising from the lower incidence of graft failure (21.6% with Prograf versus 18.3% with Advagraf) in the larger proportion of adherent patients in the Advagraf arm. In a hypothetical transplant centre of 100 kidney-transplant recipients, this would result in cost savings approaching £375,000 over 5 years.ConclusionConversion of renal transplant recipients from Prograf to Advagraf was associated with lower pharmacy and dialysis costs, with the reduction in dialysis costs being driven by improved adherence to Advagraf regimen and the consequent improvement in graft survival.

The Impact of Pretransplantation Serum Albumin Levels on Long-Term Renal Graft Outcomes

BackgroundThe association between pretransplantation serum albumin concentrations and renal graft outcomes is unclear. Hypoalbuminemia is a strong predictor of cardiovascular and all-cause mortality in chronic renal disease. Protein-energy wasting in dialysis patients is associated with irreversible damage and an increased risk of adverse outcomes. In this retrospective study, we investigated the association between preoperative albumin levels and short-term as well as long-term renal graft outcomes. Materials and MethodsWe included 375 renal transplant recipients in our center between 1991 to 2011, who were grouped according to their preoperative serum albumin levels: group I (<3.5 g/dL), group II (3.5–3.9 g/dL), group III (4.0–4.4 g/dL), and group IV (≥4.5 g/dL). We measured the frequencies of delayed graft function (DGF), acute rejection episodes, and viral infections as well as the long-term graft outcomes. ResultDGF affected 12.8%, 6.8%, 7.7%, and 9.3% of patients in groups I–IV, respectively. Acute rejection occurred in 27.7%, 27.2%, 31.6%, and 24.1%, while cytomegalovirus (CMV) and fungal infection occurred in 12.8% (6.4%), 23.3% (5.8%), 16.2% (2.6%), and 11.1% (5.6%) of patients, respectively. Serum creatinine levels at 12 months were not significantly different among the groups. Long-term graft survival was poorest in group I and best in group IV (P = .039). A Cox proportional hazards model showed group IV compared with group displayed the lowest relative risk of graft failure (hazard ratio [HR] = .536; P = .029). ConclusionsLow pretransplantation serum albumin levels were associated with poor long-term graft outcomes and with more post-transplantation complications. It may be necessary to focus on improving patients' nutritional status prior to transplantation to ensure long-term renal graft survival.

Quantitative Tc-99m DTPA renal transplant scintigraphy predicts graft survival in the very early postoperative period

Early evaluation of renal allograft prognosis is important for identification and targeted management of 'at-risk' grafts but is difficult in the absence of established tests. Tc-99m diethylene triamine pentaacetic acid renal transplant scintigraphy is a useful noninvasive method for assessing graft function. We aimed to assess the relative role of quantitative scintigraphic parameters in the immediate postoperative period for the assessment of short-term and long-term prognoses. Data from 290 dynamic renal transplant scintigraphy procedures, performed on 161 recipients on day 1 (D1) or day 4 (D4) after transplantation, were analysed to derive various perfusion parameters [Kirchner's Index, Hilson's Index (HI), kidney-to-aorta ratio and ΔP] as well as nonperfusion parameters (graft washout t (1/2), P : PI ratio, P : U ratio, R20/3, T10 and T20) using regions of interest within the whole renal graft and iliac artery. Information on graft survival up to 1 year (as a measure of short-term prognosis) and serum creatinine at 1 year (regarded as a predictor for longer-term prognosis) was collected. Mann-Whitney tests, receiver-operating characteristic curve analyses and odds ratios were used to assess the utility of each parameter in stratifying the risk for graft failure within 1 year. Correlations between each parameter and 1-year serum creatinine were tested using Spearman's rank correlation. Eleven grafts failed within 1 year. All perfusion parameters on both D1 and D4 showed significant differences between the failure and survival groups (P=0.026-0.0005). No significant between-group differences were observed for nonperfusion parameters except for R20/3 on D1 (P=0.0298). Receiver-operating characteristic analysis showed moderate accuracy for HI and ΔP on both D1 and D4 (area under the curve: 0.73-0.84); ΔP of longer than 6.0 s on D4 was associated with 24.9 times higher relative risk for graft failure within 1 year (sensitivity 88% and specificity 83%). For the assessment of long-term prognosis, a moderate correlation was found between most perfusion parameters (Kirchner's Index, HI and kidney-to-aorta ratio on both D1 and D4) and 1-year serum creatinine (ρ=0.40-0.50; P ≤ 0.0001). The nonperfusion parameters showed only weak correlation. Perfusion assessment using HI and ΔP is useful in the assessment of graft prognosis. This can be achieved as early as D1 and D4 after transplantation.

Effect of Pretransplant Dialysis Modality and Duration on Long-Term Outcomes of Children Receiving Renal Transplants

Adults receiving preemptive renal transplants have better allograft survival. Our study investigated differences in graft and patient survival based on need for, and duration of, pretransplant dialysis in pediatric renal transplant recipients. Data on pediatric kidney transplants from January 1995 to December 2000 from the Organ Procurement and Transplantation Network were included. Multivariable Cox proportional hazards analysis was performed to determine the effect of pretransplant dialysis on graft and patient survival. Of 3606 transplants, 28% were preemptive, 38% followed pretransplant hemodialysis (HD), and 34% peritoneal dialysis (PD). The 1-year acute rejection rate was lowest for the preemptive group (36%) compared with the HD (45.5%; P=0.0002) and PD (44.2%; P=0.0008) groups. On multivariable analysis, an increased relative risk of graft failure was seen with, among other variables, deceased donor transplantation and acute rejection within the first year, but not with pretransplant dialysis. When analyzed separately by donor source, pretransplant dialysis had no effect on graft survival for deceased donor graft recipients, whereas for living donor recipients, the use and duration of pretransplant HD adversely affected pediatric renal graft survival in a linear manner. No such effect was seen with pretransplant PD. There is a linear increase in the risk of graft failure with the use of and increasing duration of pretransplant HD for living donor grafts. This indicates another reason to minimize the need for and duration of pretransplant HD in children with chronic kidney disease.

Effect of Glaucoma on Corneal Graft Survival According to Indication for Penetrating Keratoplasty

To determine whether the risk of graft failure in patients with glaucoma is dependent on the indication for penetrating keratoplasty (PK). Retrospective cohort study. All patients on the United Kingdom Transplant Registry undergoing their first PK over a 7-year period with at least 1 year of follow-up were included. Data were collected on indication for PK, presence and management of glaucoma, graft diameter, recipient risk factors, and graft survival. Kaplan-Meier survival curves, a Cox regression model, and χ(2) and t tests were used in group comparisons. A total of 6255 transplants in eyes without glaucoma and 1994 in eyes with glaucoma were analyzed. Three-year transplant survival was 86% and 72% respectively (P < .0001), and 73% in eyes with medically managed glaucoma compared to 63% in surgically managed glaucoma (P = .07). Glaucoma patients undergoing PK for pseudophakic bullous keratopathy or Fuchs dystrophy had significantly increased relative risks of graft failure (1.5 and 1.9 with topical and 2.0 and 3.1 with oral antiglaucoma medication respectively, compared to those without glaucoma). There was no equivalent significant difference for those with keratoconus, previous noncataract ocular surgery, trauma, or noninfectious ulcerative keratitis. Endothelial decompensation accounted for a significantly greater proportion of graft failure in recipients with glaucoma (topical [9%] and oral medication [13%]) than in those without glaucoma (3%) (P < .001). The presence of glaucoma carries an increased risk of graft failure, in particular from endothelial decompensation. This risk is, however, also dependent on the indication for PK, with transplants undertaken for primary corneal endothelial disease carrying a higher risk.

Erythropoietin Resistance as Surrogate Marker of Graft and Patient Survival in Renal Transplantation: 3-Year Prospective Multicenter Study

Background Some transplant recipients demonstrate an inadequate response to erythropoiesis-stimulating agents, or so-called erythropoietin (Epo) resistance. The cause is multifactorial. Resistance to EPO may entail a poor prognosis for the graft and the patient, although results in the literature are inconsistent, and long-term follow-up is lacking. Objective To evaluate whether the presence of Epo resistance at the beginning of the study was a predictive factor for graft and patient survival. Materials and Methods From 482 renal transplant recipients (Kidney Disease Outcomes Quality Initiative stage 3–4T) receiving Epo-stimulating agents in the Anemia and Renal Transplantation in Spain study, 101 were selected for the present study. Erythropoietin resistance was defined as a ratio of weekly Epo dosage/hemoglobin concentration >486,94 U/g/dL with a hemoglobin/<11 g/dL. Darbepoetin dosage was calculated in Epo equivalent units, with a 1:200 conversion factor. Patients were grouped as Epo-resistant (ER+) or not Epo-resistant (ER−), to assess whether Epo resistance was predictive of patient and graft survival. Results There were no differences in demographic data between the 2 groups except for a higher incidence of vascular, interstitial, and diabetes-related causes of chronic renal failure in the ER+ group. At 3 years posttransplantation, graft survival was 33% in the ER+ group vs 58% in the ER− group ( P = .06), and patient survival was 52% in the ER+ group vs 88% in the ER− group ( P = .008). Using a Cox regression model, at 3 years, the relative risk of graft failure was 1.96 in the ER+ group (95% CI, 0.93–3.12; P = .07), and of patient death was 3.9 (95% confidence interval, 1.30–11.63; P = .01). Conclusion Erythropoietin resistance is an independent risk factor for death after renal transplantation.

Impact of the donor risk index on the outcome of hepatitis C virus-positive liver transplant recipients

We have investigated the impact of the donor risk index (DRI) on the outcome of hepatitis C virus (HCV)-infected patients undergoing liver transplantation (LTx). Retrospective analysis was performed from the Organ Procurement and Transplantation Network database (January 1, 2000 to June, 2006). The DRI was calculated as described by Feng et al. (Am J Transplant 2006;6:783-790). Model for End-Stage Liver Disease (MELD) exceptions were excluded from the analysis. Relative risk (RR) estimates of patient and graft loss were derived from Cox regression models. The Wald test was used to test the effect of the MELD score at transplant on the HCV-DRI interaction. Of the LTx recipients (16,678), 76.1% were Caucasian, and 66.7% were male; the median age was 52 (range, 18-80 years), and the mean follow-up time was 1148 days (range, 0-2959 days). Forty-six percent (n = 7675) of LTx recipients were HCV(+). The median DRI was 1.3 (range, 0.77-4.27). Increasing DRI was associated with a statistically significant increase in the RR of graft failure and patient death for both HCV(+) and HCV(-) recipients. However, HCV(+) recipients demonstrated a significantly higher increase in the RR of patient and graft loss as a function of the DRI than HCV(-) subjects, even after adjustments for several recipient factors, including MELD. In conclusion, a synergistic interaction between donor DRI and recipient HCV status exists, such that an allograft from a high-DRI donor more adversely affects the outcome of an HCV(+) recipient than that of an HCV(-) recipient.

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.

Utilization of Extended Donor Criteria Liver Allograft: Is the Elevated Risk of Failure Independent of the Model for End-Stage Liver Disease Score of the Recipient?

The goal of this analysis was to determine if outcomes from the use of extended criteria donor (ECD) livers were dependent upon the Model for End-Stage Liver Disease (MELD) score of the recipient. The Organ Procurement and Transplantation Network (OPTN) database as of March 4, 2006 was used for the analysis. Data from 12,056 adult liver transplant (LTx) recipients between June 1, 2002 and June 30, 2005 was analyzed. The donor risk index (DRI) was calculated as previously reported. A DRI of > or =1.7 was classified as ECD. Relative risk (RR) estimates were derived from Cox regression models adjusted for DRI, recipient MELD, age, sex, ethnicity, diagnosis, and year of transplant. Data from 2,873 grafts falling in the ECD category (23.8%) and their recipients were analyzed. Recipients with low MELD scores (<15) received the highest proportion of ECD livers (33%). ECD livers were associated with a significant increase in the RR of graft failure within each MELD category. However, this effect held within each of the three MELD categories. The use of ECD grafts expands the organ pool at expense of increased RR of liver failure. Our analysis showed no significant interaction between DRI and MELD score of the recipient. The fact that there is no additional impact of ECD livers in recipients with high MELD scores suggests that this group of patients may benefit from this pool of grafts.

Renal Graft Survival and Calcineurin Inhibitor

Tacrolimus is associated with fewer acute rejections than cyclosporine, but a greater risk of new onset diabetes mellitus. When compared to no tacrolimus among nondiabetics in a large patient registry, it is associated with improved graft survival. The current study used the same patient registry to compare more correctly graft survival between nondiabetic renal transplant recipients initially immunosuppressed with either of the two most frequently used calcineurin inhibitors, tacrolimus or modified cyclosporine (CsA). We examined data provided by the United States Renal Data System (USRDS) on all first, single-organ, renal transplants to nondiabetic recipients that occurred during the years 1996 to 2000. Importantly, we then limited the study to patients on CsA (n = 7,867) or tacrolimus (n = 3,082) as the initial agent. Patients with both or neither were excluded. We used Cox proportional hazards regressions to estimate the tacrolimus-related relative risk of graft failure, controlling for other significant donor, recipient, and transplant characteristics We found that tacrolimus patients had graft failure rates equivalent to those of CsA patients (hazard ratio= 1.031, P = 0.631) Although tacrolimus is being used with increasing frequency, analyses of the USRDS data show no net advantage in the ultimate transplantation outcome, graft survival. Given the higher acquisition price of tacrolimus compared to CsA and the similar risk of graft failure, further studies should be conducted to define those patient groups for which tacrolimus might be cost-effective.

Outcome of Graft Central Thickness After Penetrating Keratoplasty

To analyze the outcome of graft central thickness after penetrating keratoplasty. Retrospective observational cohort study. Eight hundred fifty-six consecutive penetrating keratoplasties (772 patients) performed between 1992 and 2001 were analyzed and 772 were included (1 graft per patient was included). Slit-lamp examination and ultrasound pachymetry. Slit-lamp findings, intraocular pressure, and graft central thickness were recorded. Patients were observed for an average of 55 months. The 36- and 60-month graft survival estimates were, respectively, 77.2% and 71.0%. The average graft central thickness in successful transplants was 655 microm at 1 week, 558 microm at 1 month, 533 microm at 6 months, 538 microm at 12 months, 558 microm at 24 months, 561 microm at 36 months, and 568 microm at 5 years. At each postoperative time point, the percentage of eyes with decreased, normal, and increased graft central thickness was significantly different according to slit-lamp findings. Of the patients with increased graft thickness, 46.2% had a simple outcome (normal intraocular pressure and normal slit-lamp findings), 28.6% experienced rejection, 15.8% experienced a graft nonimmunological event, and 9.4% experienced increased intraocular pressure. At each postoperative follow-up, subsequent graft survival was significantly lower in patients with increased graft thickness as compared with patients with normal or decreased graft thickness. When analyzing only patients with simple outcome, the relative risk of graft failure was 3.3 if graft thickness was increased at 1 month (P<0.0001). In conclusion, graft central thickness assessed by ultrasound pachymetry is a useful method for observing patients who have undergone penetrating keratoplasty. Even when slit-lamp examination reveals no complications, patients with an increase in graft thickness above the upper limit of normal for the postoperative time point under consideration are at greater risk of failure.