Long-term Kidney Transplant Survival Research Articles

Long-term Kidney Transplant Survival Across the Globe.

The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

Predicting long-term outcomes of kidney transplantation in the era of artificial intelligence

The ability to accurately predict long-term kidney transplant survival can assist nephrologists in making therapeutic decisions. However, predicting kidney transplantation (KT) outcomes is challenging due to the complexity of the factors involved. Artificial intelligence (AI) has become an increasingly important tool in the prediction of medical outcomes. Our goal was to utilize both conventional and AI-based methods to predict long-term kidney transplant survival. Our study included 407 KTs divided into two groups (group A: with a graft lifespan greater than 5 years and group B: with poor graft survival). We first performed a traditional statistical analysis and then developed predictive models using machine learning (ML) techniques. Donors in group A were significantly younger. The use of Mycophenolate Mofetil (MMF) was the only immunosuppressive drug that was significantly associated with improved graft survival. The average estimated glomerular filtration rate (eGFR) in the 3rd month post-KT was significantly higher in group A. The number of hospital readmissions during the 1st year post-KT was a predictor of graft survival. In terms of early post-transplant complications, delayed graft function (DGF), acute kidney injury (AKI), and acute rejection (AR) were significantly associated with poor graft survival. Among the 35 AI models developed, the best model had an AUC of 89.7% (Se: 91.9%; Sp: 87.5%). It was based on ten variables selected by an ML algorithm, with the most important being hypertension and a history of red-blood-cell transfusion. The use of AI provided us with a robust model enabling fast and precise prediction of 5-year graft survival using early and easily collectible variables. Our model can be used as a decision-support tool to early detect graft status.

Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes

BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n=35 and high-level viremia, n=26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P=.002), age (OR, 1.047; 95% CI, 1.008-1.088; P=.018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P=.047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P=.004), and graft survival was lower in patients with BKVi and high-level viremia (P=.027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P=.029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P=.046) were predictors of shorter graft survival. BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Clinical Events and Renal Function in the First Year Predict Long-Term Kidney Transplant Survival.

Estimated glomerular filtration rate (eGFR) at 1 year post transplantation has been shown to be a strong predictor of long-term graft survival. However, intercurrent events (ICEs) may affect the relationship between eGFR and failure risk. The OPTN and USRDS databases on single-organ kidney transplant recipients from 2012 to 2016 were linked. Competing risk regressions estimated adjusted subhazard ratios (SHRs) of 12-month eGFR on long-term graft failure, considering all-cause mortality as the competing risk, for deceased donor (DD) and living donor (LD) recipients. Additional predictors included recipient, donor, and transplant characteristics. ICEs examined were acute rejection, cardiovascular events, and infections. Cohorts comprised 25,131 DD recipients and 7471 LD recipients. SHRs for graft failure increased rapidly as 12-month eGFR values decreased from the reference 60 ml/min per 1.73 m2. At an eGFR of 20 ml/min per 1.73 m2, SHRs were 13-15 for DD recipients and 12-13 for LD recipients; at an eGFR of 30 ml/min per 1.73 m2, SHRs were 5.0-5.7 and 5.0-5.5, respectively. Among first-year ICEs, acute rejection was a significant predictor of long-term graft failure in both DD (SHR=1.63, P<0.001) and LD (SHR=1.51, P=0.006) recipients; cardiovascular events were significant in DD (SHR=1.24, P<0.001), whereas non-CMV infections were significant in the LD cohort (SHR=1.32, P=0.03). Adjustment for ICEs did not significantly reduce the association of eGFR with graft failure. Twelve-month eGFR is a strong predictor of long-term graft failure after accounting for clinical events occurring from discharge to 1 year. These findings may improve patient management and clinical evaluation of novel interventions.

Urinary metabolites give new clues to kidney transplant tolerance.

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. While the procedure is very successful in the first years following transplantation, long-term rejection of allografts remains a major problem despite immunosuppression and a further difficulty is the worldwide shortage of organs suitable for transplant. There is therefore a tremendous need to identify new therapeutic pathways that could be targeted to improve the long-term survival of kidney transplants.

Effects of Artificial Intelligence-Derived Body Composition on Kidney Graft and Patient Survival in the Eurotransplant Senior Program.

The Eurotransplant Senior Program allocates kidneys to elderly transplant patients. The aim of this retrospective study is to investigate the use of computed tomography (CT) body composition using artificial intelligence (AI)-based tissue segmentation to predict patient and kidney transplant survival. Body composition at the third lumbar vertebra level was analyzed in 42 kidney transplant recipients. Cox regression analysis of 1-year, 3-year and 5-year patient survival, 1-year, 3-year and 5-year censored kidney transplant survival, and 1-year, 3-year and 5-year uncensored kidney transplant survival was performed. First, the body mass index (BMI), psoas muscle index (PMI), skeletal muscle index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) served as independent variates. Second, the cut-off values for sarcopenia and obesity served as independent variates. The 1-year uncensored and censored kidney transplant survival was influenced by reduced PMI (p = 0.02 and p = 0.03, respectively) and reduced SMI (p = 0.01 and p = 0.03, respectively); 3-year uncensored kidney transplant survival was influenced by increased VAT (p = 0.04); and 3-year censored kidney transplant survival was influenced by reduced SMI (p = 0.05). Additionally, sarcopenia influenced 1-year uncensored kidney transplant survival (p = 0.05), whereas obesity influenced 3-year and 5-year uncensored kidney transplant survival. In summary, AI-based body composition analysis may aid in predicting short- and long-term kidney transplant survival.

Chronic Allograft Injury.

With the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.

Renal vascular resistance is increased in patients with kidney transplant

BackgroundDespite improvement in short-term outcome of kidney transplants, the long-term survival of kidney transplants has not changed over past decades. Kidney biopsy is the gold standard of transplant pathology but it’s invasive. Quantification of transplant blood flow could provide a novel non-invasive method to evaluate transplant pathology. The aim of this retrospective cross-sectional pilot study was to evaluate positron emission tomography (PET) as a method to measure kidney transplant perfusion and find out if there is correlation between transplant perfusion and histopathology.MethodsRenal cortical perfusion of 19 kidney transplantation patients [average time from transplantation 33 (17–54) months; eGFR 55 (47–69) ml/min] and 10 healthy controls were studied by [15 O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy.ResultsRenal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4–4.0) ml min− 1 g− 1 and 2.2 (2.0–3.0) ml min− 1 g− 1, respectively (p = 0.1). Renal vascular resistance (RVR) of the patients was 47.0 (36.7–51.4) mmHg mL− 1min− 1g− 1 and that of the healthy 32.4 (24.6–39.6) mmHg mL− 1min−1g−1 (p = 0.01). There was a statistically significant correlation between Doppler RI and perfusion of transplants (r = − 0.51, p = 0.026). Transplant Doppler RI of the group of mild fibrotic changes [0.73 (0.70–0.76)] and the group of no fibrotic changes [0.66 (0.61–0.72)] differed statistically significantly (p = 0.03). No statistically significant correlation was found between cortical perfusion and fibrosis of transplants (p = 0.56).Conclusions[15 O]H2O PET showed its capability as a method in measuring perfusion of kidney transplants. RVR of transplant patients with stage 2–3 chronic kidney disease was higher than that of the healthy, although kidney perfusion values didn’t differ between the groups. Doppler based RI correlated with perfusion and fibrosis of transplants.

The impact of donor/recipient age difference and HLA mismatch on graft outcome in pediatric kidney transplantation.

Understanding the relationship between the factors that influence long-term kidney transplant survival remains a key priority for pediatric nephrologists. We assessed the relative impact of donor/recipient age difference and HLA matching on long-term graft outcomes. We conducted a retrospective cohort study of pediatric and adolescent recipients who received a primary kidney transplant in Australia and New Zealand between January 1, 1990, and December 31, 2015. The primary outcome was graft survival analyzed by Kaplan-Meier method. During the 26-year period, 1134 primary (395 DD and 739 LD) kidney transplants were performed in recipients less than 20years of age. The median follow-up time was 10.2years. Overall, 405 patients (35.7%) lost their transplant with graft survival 93.8% at 1year, 82.5% at 5years, 65.8% at 10years, and 49.9% at 15years post-transplant. There was consistently higher graft loss of DD kidneys as compared to LD kidneys at each time point. Both increasing donor/recipient age difference (aHR 1.11 per 10years; 95% CI, 1.02-1.20; P=0.009) and increasing HLA mismatch (aHR 1.20 per mismatch; 95% CI, 1.10-1.30; P<0.001) were associated with decreased graft survival. Donor/recipient age difference and HLA matching are important factors influencing long-term graft outcomes in pediatric kidney transplantation. HLA mismatch remains a strong predictor of graft loss. For patients without the option of a LD, we suggest that the degree of HLA mismatch should not be discounted as part of the decision-making process of organ allocation.

The Impact of Donor/Recipient Age Difference and HLA Matching on Graft Outcome in Pediatric Kidney Transplantation

Introduction Understanding the relationship between the factors that influence long-term kidney transplant survival in order to appropriately select the optimal initial graft remains a key priority for pediatric nephrologists. Materials and Methods Using the ANZDATA database, we conducted a retrospective cohort study of pediatric and adolescent primary kidney transplant recipients to assess the relative impact of donor/recipient age difference and HLA mismatches on long-term graft outcomes. The study population included all kidney transplant recipients less than 20 years of age who received a primary kidney transplant in Australia and New Zealand between January 1, 1990 and December 31, 2015. The primary outcome was graft survival following first kidney transplant analysed according to the Kaplan-Meier method. Secondary outcomes included delayed graft function (requiring dialysis in the first 72 hours post-transplant) and graft function at 12 months, as a surrogate marker of long term graft survival. Results and Discussion During this 26-year period, 1134 primary kidney transplants were performed in recipients less than 20 years of age. The median follow-up time after the first graft transplant was 10.2 years (IQR 4.2-16.3 years), with 30 recipients lost to follow up (2.6%). During the study period, 405 patients (35.7%) lost their graft with graft survival of 93.8% (95% CI, 92.4%-95.2%) at 1 year post-transplant, 82.5% (95%CI 80.6%-84.4) at 5-years, 65.8% (95% CI, 62.5-69.1%) at 10 years and 49.9% (95% CI, 46.9-54.1%) at 15 years. There was consistently higher graft loss of deceased donor kidneys as compared to live donor kidneys at each time point. On Cox proportional hazards regression, both increasing donor/recipient age difference (adjusted hazard ratio [aHR] 1.09 per 10 years; 95%CI, 1.01-1.18; p=0.03) and increasing HLA mismatch (aHR 1.19 per mismatch; 95%CI, 1.10-1.30; p<0.001) were associated with decreased graft survival. In addition, graft failure was associated with the following factors: Indigenous/Pacific Islander race (when compared to Caucasian race, p<0.001), glomerulonephritis as a cause of ESKD (when compared to CAKUT; p=0.01), use of T-cell or other induction agents (when compared to basiliximab; p=0.009) and increasing recipient age at kidney transplant (p<0.001), when adjusted for baseline immunosuppression. Conclusion Both donor/recipient age difference and HLA matching are important factors influencing long-term graft outcomes in pediatric kidney transplantation and HLA mismatch remains a strong predictor of graft loss. For pediatric patients without the option of a live donor, we suggest that along with age of the donor and other markers of kidney quality, the degree of HLA mismatch should not be discounted as part of the decision making process in deceased donor allocation. ANZDATA.

Complement Alternative Pathway Deficiency in Recipients Protects Kidney Allograft From Ischemia/Reperfusion Injury and Alloreactive T Cell Response.

Despite the introduction of novel and more targeted immunosuppressive drugs, the long-term survival of kidney transplants has not improved satisfactorily. Early antigen-independent intragraft inflammation plays a critical role in the initiation of the alloimmune response and impacts long-term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive antigraft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we speculated whether selective blockade of AP could be a strategy for prolonging kidney graft survival. Here we showed that Balb/c kidneys transplanted in factor b deficient C57 mice underwent reduced IRI and diminished T cell-mediated rejection. In in vitro studies, we found that fb deficiency in T cells and dendritic cells conferred intrinsic impaired alloreactive/allostimulatory functions, respectively, both in direct and indirect pathways of alloantigen presentation. By administering anti-fB antibody to C57 wt recipients in the early post Balb/c kidney transplant phases, we documented that inhibition of AP during both ischemia/reperfusion and early adaptive immune response is necessary for prolonging graft survival. These findings may have implication for the use of AP inhibitors in clinical kidney transplantation.

Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.

B Cells and Kidney Transplantation

Despite advances in immunosuppression over the last three decades, long-term kidney transplant survival is suboptimal,[1][1] and mechanisms of late graft injury are incompletely understood. There remains a need for identifying and validating biomarkers capable of accurately stratifying patients into

Reduction of chronic rejection of renal allografts by anti-transforming growth factor-β antibody therapy in a rat model

There is no effective treatment for chronic rejection (CR) that largely limits long-term survival of kidney transplants. Transforming growth factor (TGF)-β is a fibrogenic factor for tissue fibrosis. This study was to test the efficacy of an anti-TGF-β antibody in preventing the CR of renal allografts in a preclinical model. Male Lewis rats (RT1¹) were orthotopically transplanted with donor kidneys from male Fischer 344 (RT11v1) rats and were treated with either anti-TGF-β or a control antibody. The CR of renal allografts was assessed by semiquantitative histological analyses, and intragraft cytokines and fibrosis-related genes ware examined by PCR arrays. Compared with the control antibody, anti-TGF-β antibody treatment significantly reduced recipients' proteinuria (P = 0.0002), and CR in renal transplants, which was indicated by the fewer injured renal tubules, glomeruli, and interlobular arterioles or arteries, and by less mononuclear cell infiltration and interstitial fibrosis in the anti-TGF-β antibody-treated group (P < 0.05), but not significantly attenuate the ratios of different infiltrating leukocytes. These pathological changes were associated with downregulation of TGF-β1, TGF-β2, and proinflammatory cytokines, or with upregulation of anti-fibrotic HGF, BMP5, and BMP7. The therapeutic effect of the anti-TGF-β antibody was further confirmed by its prevention of graft dysfunction, indicated by lower levels of serum creatinine and blood urea nitrogen or higher creatinine clearance in anti-TGF-β antibody-treated recipients compared with those in control recipients (P < 0.05). In conclusion, the anti-TGF-β antibody (1D11) treatment significantly reduces CR of renal allografts in rats, suggesting the therapeutic potential of this antibody therapy for treating CR of kidney transplants in patients.

ESAs in Transplant Anemia

ESAs in Transplant Anemia

Renal tubular epithelial cells as immunoregulatory cells in renal allograft rejection

Kidney transplantation is the best therapeutic option for patients with end-stage kidney disease. However, the long-term survival of kidney transplants still remains relatively poor even under potent immunosuppression. Thus, it is necessary to further review the pathogenesis of renal allograft failure. Here, we discuss the potential impact of activated resident tubular epithelial cells (TECs) on infiltrating leukocyte responses on renal allograft failure. Immunohistochemical staining or in situ hybridization of renal allograft biopsies shows that activated TECs produce inflammatory cytokines and may act as nonprofessional antigen-presenting cells in the response to stimulation from leukocyte infiltration. Further experimental studies confirm that by a feedback loop, activated TECs positively or negatively regulate the destructive activity of infiltrating leukocyte through (1) alteration of leukocyte activation, proliferation, differentiation, and migration to the graft through secretion of cytokines and chemokines; and (2) direct regulation of infiltrating T-cell function through cell-cell contact. Specifically targeting kidney factors has significant impact on renal graft damage or kidney disease. This review suggests that graft TECs can regulate intragraft immune responses, and modulation of specific graft TEC responses as a therapeutic strategy may benefit long-term survival of kidney transplants.

Evolution of the Renal Function is a Better Predictor of Long-Term Survival Than Serum Creatinine

Background In recent years acute rejection has decreased to 10% to 20%. Therefore it is necessary to look for new endpoints in renal transplantation. Serum creatinine and changes in creatinine have been reported to be powerful predictors of long-term kidney transplant survival. Chronic renal allograft nephropathy is the primary cause of long-term graft failure but may appear at any stage in the evolution. Methods Data from 315 patients receiving cadaver donor renal transplants between February 1987 and March 2001 that functioned for 1 year were examined for the influence of demographic characteristics and transplant variables. Creatinine clearance was estimated using the Cockroft-Gault formula. Survival was assessed with the actuarial method. The multivariate analyses were performed using Cox proportional hazard models. Results The 10-year graft survival showed a relative risk of 2.5 in the univariate analysis when there was more than 10% decrease in renal function at 3 months compared with nadir values. When the decrease was more than 25% of creatinine clearance at the third month, during the evolution and serum creatinine at 3 months introduced in the multivariate model, the latter was not significant, while the other variables had a RR of 4.4 and 10, respectively. Conclusion The evolution of renal function at 3 months and throughout the evolution were better predictors of graft failure than an isolated serum creatinine value.

Influence of kidney function to the impact of acute rejection on long-term kidney transplant survival

In kidney transplantation, timing of an initial acute rejection (AR) is correlated with a variable risk of graft loss. However, it is unknown whether the increased risk for graft loss because of AR is conditioned by impaired graft function. A total of 730 cadaveric kidney transplant recipients were retrospectively evaluated from 1994 to 2001. When AR occurred, the risk ratio (RR) for graft loss was strongly time-dependent and increased, the later the rejection episode occurred. Compared with the reference group (no rejection) having an AR within 0-30, 31-365, or >365 days post-transplant conferred a 3.1-, 9.1- and 49.3-fold risk for subsequent graft loss (P < 0.001). By including serum creatinine as an indicator for graft function at the time of rejection RR decreased to 2.4-, 7.1- and 21.8-fold, but remained still significant (P = 0.023). In conclusion, the higher risk of graft loss after late AR is not fully explained by impaired graft function measured by serum creatinine.

CAN SERUM CREATININE IN THE FIRST YEAR AFTER TRANSPLANT PREDICT LONG-TERM RENAL TRANSPLANT OUTCOME?

P349 Aims: As short-term renal transplant survival continues to improve, with known risk factors having a diminishing effect, attention is increasingly focussing on alternative measures of outcome such as renal function. This study explores the relationship between renal function in the first year after transplant and long-term kidney transplant survival in the UK. Methods: Cadaveric heartbeating donor kidney only transplants in adult patients in the UK between 1983 and 1987 were analysed. Transplants failing in the first year were excluded. For 75% of the remaining cohort, both 3 and 12-month serum creatinine measures were recorded on the UK’s national transplant database. Transplant survival analysis (death with function counted as a failure) considered the influence on ten-year outcome of 3 and 12-month serum creatinine; the change between 3 and 12 month serum creatinine (Δ creatinine) and other potential risk factors recorded. Data were available for 2766 transplants with 97% 10-year follow-up including 17% regrafts, which were analysed separately. Results: Analysis of first transplants showed a highly statistically significant association between ten-year transplant survival and 12-month creatinine, Δ creatinine and an interaction of the two (p<0.0001). Unadjusted 10-year transplant survival estimates ranged from 62% (95% confidence interval (CI) 58-65%) for transplants with 12-month serum creatinine <120 μmol/l to 13% (95% CI 9-18%) for those with 12-month creatinine >= 265 μmol/l. There was a negative association between outcome and Δ creatinine, which was greatest for those with poor function at 12-months. Other factors adjusted for were recipient age (p<0.0001), blood group (p<0.001) and HLA match (p<0.1). Univariately, donor age and donor-recipient gender match were significant, but these effects disappeared with the introduction of measures of post-transplant renal function. Analysis of regrafts and of graft (death-censored) survival both showed comparable results. The relevance of findings to more recent data was validated by analysis of 3-year outcome of a recent cohort. Conclusions: For transplants functioning after the first post-operative year, 12-month serum creatinine and Δ creatinine were highly predictive of 10-year transplant survival. There was a 49% survival difference at 10-years post-transplant between the group with the poorest renal function at one year and the group with the best function.