Renal Graft Survival Research Articles

Pediatric renal transplantations: Does the etiology of renal insufficiency influence graft survival?

PURPOSE Urological abnormalities account for 20 to 30 % of end-stage renal disease (ESRD) in children. This study evaluates whether the etiology of end-stage renal disease (urological x nephrological) has an influence on graft survival. MATERIAL AND METHODS We evaluated retrospectively from February 1990 to January 2007, 523 pediatric renal transplantations (<18 years of age) at our institution. Patients were separated into two groups according to etiology of ESRD: G1 nephrological and G2 urological. The groups were matched with respect to immunosuppression regime and donor type. Renal function was assessed by means of creatinine levels. RESULTS The average age for G1 was 15 (2 to 17 years of age) and for G2 11.5 (4 to 17 years of age). G1 was composed of 205 male and 173 female patients and G2 included 90 males and 55 females. In G1, 378 renal transplantations were performed: glomerulonephritis 105, focal glomerular sclerosis 76, indeterminate 102 and miscellaneous 95. In G2, 145 renal transplantations were performed in patients with: posterior urethral valve 40, vesicoureteral reflux 39, neurogenic bladder 16, and miscellaneous 50. Urinary tract infection was present in 17% of G1 patients and in 36% of G2. Acute rejection was higher in G1 (25% vs 11%). Renal graft survival at one year was 89% in G1 and 90% in G2, at five years 77% in G1 and 78% in G2 and at 10 years 62% in G1 and 61% in G2. CONCLUSIONS The etiology of renal insufficiency does not influence survival of renal grafts, when comparing nephrological and urological etiology.

Renal transplantation with and without bladder augmentation in children posterior urethral valve is there a difference in the long term?

PURPOSE Posterior urethral valve (PUV) is a common etiology of end-stage renal disease(ESRD) in children. We compared children who underwent bladder augmentation prior to renal transplantation with those who underwent transplantation in the native bladder in regards to occurrence of UTI and long term renal function. MATERIAL AND METHODS We identified 40 patients with PUV from 1992 and 2006 who underwent renal transplantation in our institution. These patients were divided into two groups, Group 1: 20 patients who underwent bladder augmentation and Group 2 20 patients who did not undergo bladder augmentation. Graft dysfunction was defined as an increase of >20% in creatinine levels. RESULTS Forty-four transplantations were performed, 21 in G1 and 23 in G2, 35 from deceased donors(16 in G1 and 19 in G2). Medium age at transplantation was 11 years (5 to 17). Bladder drainage was done using clean intermittent catheterization by external continent ostomy in 95% of patients. Average renal graft survival at one year was 88% for both groups, after 5 years values were maintained of 90% in G1 and 87% in G2. Acute rejection occurred in 15% of grafts in G1 and 26% in G2. Urinary tract infection (UTI) was found in 85% of G1 and 25% of G2. An increase in creatinine of 20% above the nadir was found in 33% of G1 patients and 10% in G2. CONCLUSIONS Patients who underwent bladder augmentation had a higher incidence of infection and increase of creatinine levels, however these events did not affect renal graft survival when compared to non-augmented patients.

BK Virus Nephritis after Renal Transplantation

BK virus nephritis is an increasing problem and is posing a threat to improving renal transplant graft survival. The pathogenesis of this condition remains to be investigated. Higher prevalence of BK virus infection in recent years has been correlated with declining acute rejection rates and the use of potent immunosuppressive agents. Patients with this infection usually have asymptomatic viremia and/or nephritis with or without worsening of renal function. The diagnosis of this disease is based on detecting the virus or its effects in urine, blood, and renal tissue. In the past, approximately 30 to 60% of patients with BK virus nephritis developed graft failure. In recent years, the combination of early detection, prompt diagnosis, and therapies including preventive measures have resulted in better outcomes.

Calcineurin-inhibitor avoidance in elderly renal allograft recipients using ATG and basiliximab combined with mycophenolate mofetil

In old recipients of renal allografts from old donors, benefits of calcineurin-inhibitors (CNI) are curtailed by nephrotoxicity. Intending to improve the outcome of these recipients, we analyzed a CNI-free immunosuppressive regimen consisting of anti-thymocyte globulin (ATG), basiliximab, mycophenolate mofetil (MMF) and steroids. Kidney allograft recipients with low immunological risk (panel reactive antibodies <30%) were eligible for this study. Immunosuppression induction included ATG (4 mg/kg, day 0), basiliximab (20 mg, day 0 + 4) and steroids, followed by MMF (TL 2-6 microg/ml) and steroid maintenance treatment. Patient and graft survival rates respectively were 89.3% and 85.4% (12 months), and 86.6% and 76.8% (24 months). Delayed graft function occurred in 44.6%. S-creatinine at 12 months was 1.85 +/- 0.94 mg/dl. Thirty patients (53.6%) showed biopsy-proven rejections (6x Banff 3, 13x Banff 4I and 16x Banff 4II), 77% of which were steroid-sensitive, 23% required antibody treatment. After 12 months, 83% of the patients had an MMF-based immunosuppression, 43% were CNI-free. Cytomegalovirus (CMV) infections occurred in 28, tissue-invasive disease in three patients. Despite acceptable renal graft survival and function in some of patients with marginal organs, high incidences of rejections and CMV infections suggest the feasibility of CNI-avoidance using an MMF-based protocol only in carefully selected patients.

Cold Preservation Mediated Renal Injury: Involvement of Mitochondrial Oxidative Stress

Cold preservation has greatly facilitated the use of cadaveric kidneys for renal transplantation, but, clearly, damage occurs during both the preservation episode and the reperfusion phase (following transplantation). The aims of this study were twofold: to develop an in vivo model that was capable of evaluating renal function at early time points following cold preservation, and to evaluate the extent of renal mitochondrial damage that occurs following short periods of cold preservation in vivo. To accomplish these goals, we developed a novel rat model of in vivo renal cold ischemia followed by warm reperfusion (cold I/R) which avoided the complexity involved with transplantation. Briefly, after a right nephrectomy, cold I/R was initiated via pulsatile perfusion (40 minutes) of the left kidney with a cold University of Wisconsin solution followed by 18 hours of warm reperfusion. Cold I/R resulted in significant renal injury, nitrotyrosine production, and inactivation of the key mitochondrial antioxidant enzyme, manganese superoxide dismutase. Furthermore, the activities of the mitochondrial respiratory complexes were significantly reduced following cold I/R. In conclusion, short-term cold I/R results in inactivation of MnSOD, which may lead to the inhibition of mitochondrial complexes and subsequent renal injury. These data suggest that compounds designed to prevent early mitochondrial injury in kidneys that undergo cold preservation would significantly improve renal function and graft survival following transplantation.

Feasibility and Safety of Performing Hand-assisted Laparoscopic Donor Nephrectomy for Patients with Multiple Renal Arteries

Purpose: We wanted to present the feasibility and safety of hand-assisted laparoscopic donor nephrectomy (HALDN) for treating patients with multiple renal arteries. Materials and Methods: Between February 2000 and July 2006, 252 patients underwent HALDN. The results for the patients with a single renal artery (n=187) (Group I) and those patients with multiple renal arteries (n=65) (Group II) were compared in terms of the donor and recipient outcomes. A retrospective chart review was performed and statistical analysis included Student's t-test, the chi square test and Kaplan-Meier survival probability analysis. Results: HALDN was technically successful in 251 patients (1 patient had to be converted to open donor nephrectomy). The operative times were increased in group II, but the differences between the groups were not statistically significant. The warm ischemic times were significantly longer in group II. The intraoperative blood loss, postoperative hospital stay and complication rate in the donor group were not associated with the number of renal arteries. The recipients' renal function and overall graft survival were similar between groups I and II. Conclusions: In our single-center study, the presence of renal artery multiplicity when performing HALDN does not have a significant impact on the outcomes of the renal donors or recipients. (Korean J Urol 2008;49:443-448) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Efficacy of Equoral in Prophylactic Immunosuppression after De Novo Kidney Transplantation

AbstractBACKGROUNDCyclosporin A is a well‐known calcineurin inhibitor that has been used for prophylactic immunosuppression after organ transplantation. The aim of this study was to evaluate the efficacy and safety of a new generic cyclosporin formulation, Equoral (Teva Pharmaceuticals), in the treatment of de novo renal transplant recipients.METHODSTwenty cadaveric‐donor renal transplant recipients between 23 and 71 years of age at the time of transplantation (mean age 52 ± 12.5 years) were followed for 12 months to determine if the grafts functioned and if there were rejection attacks and side effects. In addition to cyclosporin, all patients received mycophenolate mofetil (CellCept) and prednisone (Prednison).RESULTSMean serum creatinine level decreased significantly after transplantation. In 6 of the 20 patients observed, 7 biopsies showed acute rejection episodes (35%). Over the 12‐month post‐transplant period, all patients showed stable graft function, with a mean serum creatinine level of 202.1 ± 130.9 μmol/L. Patient and renal graft survival rates were 100% after 12 months. Most of the observed adverse events were those commonly reported with the use of cyclosporin, and they resolved with a reduction in the cyclosporin dose. Equoral treatment demonstrated an acceptable safety profile with maintenance of satisfactory and stable renal function.CONCLUSIONSEquoral as a primary immunosuppressant for de novo kidney transplant recipients seems effective and safe in terms of acute rejection rate, patient and renal graft survival rates, and side effect profiles.

A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine

Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients. In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued low-dose steroid treatment (group B). During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-to-treat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P = ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P = 0.059). After 3 years, mean creatinine clearance was 52.3 +/- 17.1 ml/min in group A and 52.2 +/- 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 +/- 14.7 ml/min) and those who did not (53.6 +/- 18.3 ml/min; P = 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P = 0.0043) was more frequent in group B. Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.

Lifespan Analysis of 212 Transplanted Kidney Grafts: Effects of Use of Humanized Anti–IL-2R Monoclonal Antibody in Graft Survival at 1, 3, and 5 Years for 108 Recipients

Introduction The use of new drugs and new immunossupressant schemes, as well as induction therapy with anti-IL-2R monoclonal antibody has significantly contributed to prolonged renal graft survival, especially in cadaveric grafts. However, what has led to this improvement has not been defined yet. Objective Analyze the outcome of induction of humanized anti-IL-2R monoclonal antibodies on 1, 3 and 5 year survivals of 212 renal transplants from 1999 to 2005. Method We analyzed the lifespan of grafts using Kaplan-Meier curves, using a significance level of α = 0,05 for 212 renal allografts. Results The global result for 1, 3 and 5 year survival curves of patients who received the induction therapy was 88%, 86% and 86%, and for recipients who did not receive induction was 81%, 81% and 81%, respectively. Likewise, cadaveric donors who received induction displayed 88%, 88% and 88%, and those who did not receive it 62%, 62% and 62% (p = 0,0089). Conclusion Despite the time and the number of transplants using induction therapy being modest, at 1, 3 and 5 years there was an increased lifespan, especially for cadaveric grafts, among patients who received induction, with IL2Ra antibodies.

Protective Effects of Peroxisome Proliferator-Activated Receptor γ Ligand on Apoptosis and Hepatocyte Growth Factor Induction in Renal Ischemia-Reperfusion Injury

Renal ischemia-reperfusion injury affects the long-term outcome of renal graft survival. Thiazolidinediones (TZDs), synthetic peroxisome proliferator-activated receptor (PPAR)-gamma ligands, have been shown to exert therapeutic effects upon renal ischemia-reperfusion injury far beyond their use as insulin sensitizers. It has also been reported that hepatocyte growth factor (HGF) has a beneficial effect on renal ischemia-reperfusion injury and that TZDs induce increased HGF mRNA expression and protein secretion. We investigated the effect of troglitazone, one of the TZDs, in a rat model of renal ischemia-reperfusion injury. A 45-minute period of warm renal ischemia was induced by bilateral clamping at 37 degrees C with rats being sacrificed before the onset of ischemia and at 2, 4, 6, and 12 hr after reperfusion. The expression of PPAR-gamma was measured by reverse-transcriptase polymerase chain reaction (RT-PCR) and western blotting while the production of HGF was investigated by RT-PCR and immunohistochemistry. The effect of troglitazone treatment on the level of apoptosis was determined by staining for cleaved caspase-3 and single-stranded DNA (ssDNA). The numbers of cleaved caspase-3 and ssDNA positive cells were decreased in rats treated with troglitazone. The production of HGF mRNA and protein was most intense at 4 hr. The expression of PPAR-gamma and HGF was increased in the group treated with troglitazone compared with the control group. CONCLUSIONS.: Pretreatment of rats with the PPAR-gamma ligand troglitazone decreased apoptotic cell death in renal ischemia-reperfusion injury as a result of the induction of HGF.

The role of angiotensin II type 1 receptor-activating antibodies in renal allograft vascular rejection

Acute rejection with vascular involvement remains a challenging problem in renal allotransplantation. Fibrinoid necrosis of the arteries with secondary thrombotic occlusions is C4d negative in 50% of cases and has the worst prognosis among all allograft vascular lesions. Nonhuman leukocyte antigen (HLA) non-complement-fixing antibodies reacting to artery-specific antigens have been speculated to be responsible for causing severe vascular injury. We recently reported the presence of agonistic antibodies against the angiotensin II type 1 receptor (AT(1)R-AA) in 16 recipients of renal allografts who had severe vascular rejection and malignant hypertension but who did not have anti-HLA antibodies. AT(1)R-AA stimulate AT(1)R and induce mediators of inflammation and thrombosis. Removal of AT(1)R-AA by plasmapheresis in combination with pharmacologic AT(1)R blockade leads to improved renal function and graft survival in AT(1)R-AA-positive patients. We have shown that the analysis of the subtle diagnostic and mechanistic differences may help to identify patients at particular risk and improve outcome of rejections with vascular pathology.

Plasma adiponectin concentration in patients after successful kidney transplantation – a single-center, observational study

Adiponectin is an anti-inflammatory protein secreted almost exclusively by adipocytes which improves insulin sensitivity and presents antiatherogenic properties. Plasma adiponectin concentration is almost 3 times higher in hemodialysis patients and markedly decreased after successful kidney transplantation. However, until now, there are no studies analyzing plasma adiponectin concentration in kidney transplant patients (KTx) during the long-term period after transplantation. Therefore, the aim of present study was to examine plasma adiponectin concentration in KTx patients during the wide range of time after transplantation. Single center, cross-sectional study including 228 KTx adult recipients (143 M and 85 F) with estimated glomerular filtration rate (eGFR) > or = 15 ml/min, 80 hemodialysis patients (34 M and 46 F) and 52 healthy subjects (33 M and 19 F). Plasma adiponectin concentration was estimated together with HOMA-IR (homeostasis model assessment insulin resistance index) and plasma lipid profile. In KTx patients plasma adiponectin concentration 14.0 (13.1-15.0) microg/ml was significantly (p < 0.001), lower than in hemodialysis ones 29.0 (24.7-33.3) microg/ml, however, significantly (p < 0.001) higher than in healthy subjects 10.1 (8.8-11.5) microg/ml. Among KTx patients the highest plasma adiponectin concentration was observed in the subgroup of patients surviving with the functioning graft more than 8 years after transplantation. In KTx patients, significant, negative correlations were found between plasma adiponectin concentration and BMI (p = 0.017), HOMA-IR (p = 0.02) and estimated GFR (p < 0.009), respectively. Multiple regression analysis performed in the group of KTx patients, with plasma adiponectin concentration as the dependent variable and BMI, age, gender, estimated GFR as independent variables showed that in this model (R2 = 0.09) plasma adiponectin concentration significantly depends on BMI (p = 0.035), gender (p = 0.004) and eGFR (p = 0.023). Patients with long-term renal graft survival are characterized by a higher plasma adiponectin concentration. Kidney graft function (assessed as estimated GFR) is an important factor influencing plasma adiponectin concentration.

Cadaveric Kidney Transplantation: Five Years Experience at a Single Center

Background In the past, the majority of renal transplantations in Iran were from living donors, but recently cadaveric donation of organs is increasing. We reviewed our experience on kidney transplantation from cadaveric donors for the past 5 years in our center. Methods Between July 1998 and September 2004, 122 kidneys were removed from 61 cases of brain-dead patients and transplanted in 114 patients with end-stage renal disease in our center. Two kidneys had tumoral involvement and were discarded. Three kidneys were transplanted in other centers and three patients received en bloc kidney transplantations. In addition, we performed nine cases of heart, one case of liver, and one case of lung transplantations. All the recipients were followed for at least 1 year and posttreatment renal function and graft survival were determined. Results All cadaveric donors were brain dead due to car (30%) and motocycle (70%) accidents, with ages ranging from 5 to 56 years (mean, 24/4 years). The mean warm and total cold ischemia times were 7 minutes and 8.1 hours, respectively. The mean distance between harvesting center and our hospital was 65 km. The 1-year graft survival was 92.3%, with mean serum creatinine of 1.76 ± 0.79 at 1 year. Of other transplanted organs, the liver and lung recipients died 24 hours and 45 days after operation. Among heart recipients, four are still alive. Conclusion Cadaveric donors in developing countries including Iran can be excellent sources of organ donation.

No Association of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Gene Polymorphisms With Kidney Allograft Survival: A Multicenter Study

It has been proposed that inherited risk factors of venous thromboembolism, such as factor V G1691A (FV-Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T, might be associated with poorer survival rates of transplanted kidneys. On the basis of this hypothesis, we performed a multicenter study, involving recipients of primary and repeat kidney transplants, to investigate the potential effect of these three single nucleotide polymorphisms (SNP) on graft survival. The study consisted of 676 first and 651 retransplant patients. Using the polymerase chain reaction-sequence specific primers method, we typed all patients for the three SNP and analyzed graft survival. We could not find a statistically significant association between graft survival and factor V Leiden or MTHFR C677T genotypes. A better 3-yr graft survival was found for first transplant recipients with the genotype prothrombin 20210 G/G as compared to those with the G/A genotype (P=0.031). However, Bonferroni correction for the three SNPs investigated in this series rendered the P value insignificant (P(corrected)=0.093). We did not find a statistically significant association of SNP factor V Leiden G1691A and MTHFR C677T with renal graft survival. Prothrombin G20210A resulted in a significant association that was not sustained after Bonferroni correction. This SNP might be an interesting candidate for future studies.

Fish Oil Treatment for Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials

Calcineurin inhibitors have adverse effects that contribute to nephrotoxicity and cardiovascular risk profile, and these may be reduced by administration of fish oil. The aim of this review was to assess the benefits and harms of fish oil supplementation in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. The Cochrane Controlled Trials Registry, MEDLINE, and EMBASE were searched for randomized controlled trials of fish oil treatment in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. Trials comparing fish oil to both placebo and statins were included. Data were extracted for patient and graft survival, acute rejection, calcineurin inhibitor toxicity, cardiovascular events, adverse effects, compliance, renal function, blood pressure, and lipid profile. Dichotomous outcomes were reported as relative risk and continuous outcome measures as weighted mean differences (WMD), with 95% confidence intervals. Sixteen suitable trials were analyzed. Fish oil treatment was associated with a lower diastolic blood pressure (WMD 4.5 mmHg, P=0.004) and higher high-density lipoprotein (HDL) cholesterol (WMD 0.12 mmol/L, P=0.01) but did not affect the other outcomes. Fishy aftertaste and gastrointestinal upset were common but did not result in significant dropout. Fish oil effects on lipids were not significantly different than low-dose statins. There is insufficient evidence from currently available randomized controlled trials to recommend fish oil therapy to improve renal function, rejection rates, and patient or graft survival. Improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use.

Significance of Anti-HLA and Donor-Specific Antibodies in Long-Term Renal Graft Survival

Numerous studies have demonstrated an association of posttransplant HLA antibodies with decreased long-term graft survival. The presence of C4d deposition in these cases supports the hypothesis that antibody and complement deposition are involved in the pathogenesis of graft failure. Development of HLA antibodies may predate the clinical manifestation of chronic rejection (CR). However, frequency of donor-specific antibody is low when all patients are screened regardless of their graft function, and it may be more valuable to look for antibody only in patients with mild dysfunction. Effective treatment for CR has not been identified, although increased immunosuppression has been shown to decrease antibody levels and stabilize graft function. Many patients have been identified with good graft function despite the presence of circulating donor-specific HLA antibody. Additional studies focusing on the mechanism behind the apparent protection from the detrimental effects of antibody in such patients are needed.

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR ( n = 11) and Group UC ( n = 59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC ( P < 0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 ( P < 0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

Organ transplantation in Bulgaria

The transplantation program in Bulgaria started in 1968 with renal transplantations to a child and adult woman. In 1986 the first heart transplantation was performed. To date a total of 10 heart transplants have been performed, including one combined heart/lung. A liver transplantation program was launched in 2005 with a total number of 16 transplantations-7 from living donors and 9 from deceased donors. The highest transplantation activity is registered in the field of renal transplantation. During the period 1980-2006, 462 Bulgarian recipients of kidney were transplanted in Bulgaria. The ratio between transplantations from deceased and living related donors is approximately 1:0.9. Annual transplantation activity varies among the years from 1 to 12 renal transplantations p.m.p./per year. The 1- (80.7% vs. 63.1%), 5- (57.86% vs. 39.0%) and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of living donor kidneys compared to those of deceased donor. In 1983 a National kidney waiting list was established. Currently the number of the registered patients eligible for renal transplantation is 885. The proportion of sensitized patients in the waiting list is 20.45% and 4.34% of them are hyperimmunized. Recently HLAMatchmaker program has been implemented not only for sensitized patients but also for those with rare alleles and haplotypes. Post-transplant immunological monitoring showed a strong association between alloantibody presence and delayed graft function (Chi-square=10.73, P<0.001), acute rejection (Chi-square=14.504, P<0.001), chronic rejection (Chi-square=12.84, P<0.001) and graft loss (Chi-square=20.283, P<0.001). Based on the experience in our transplant center a strategy for improvement of long-term renal graft survival was developed and implemented.

P255: Meta-analysis demonstrates that obesity does decrease renal transplant graft survival

There has been controversy as to the effect of moderate obesity on kidney transplant survival In general, registry studies have demonstrated an adverse effect of obesity on one year graft survival while single center studies generally have not. We suspected that this was due to type II error and a skewed distribution in which most studies had more control subjects than obese subjects. To resolve this dichotomy, we performed a detailed search for single center studies with comparable experimental design and a threshold for obesity as body mass index between 25 and 30.. We subjected the one-year graft survival (not death-censored) to meta-analysis. The results are detailed below. All studies reviewed had an odds ratio greater than one, indicating that all found increased graft loss associated with obesity. No single study had p < 0.05, indicating that the number and distribution of subjects in each study was not sufficient to achieve statistical significance. However, when analyzed together in a random effects meta-analysis, the aggregate odds ratio was 1.783 with p = 0.007. This is highly comparable to the results seen in registry studies, notably Meier-Krische, et. al., Transplantation 73: 70 2002. We conclude that despite apparent dichotomy there is substantial agreement between the single center and registry studies: that moderate levels of obesity are associated with poorer graft survival following kidney transplantation. Further analysis should be pursued as to the effectiveness of weight-loss strategies in reversing this finding. It would appear that the treatment of predialysis- and pretransplant- renal failure patients should place much greater emphasis in diet, exercise, and weight control.

The association between recipient alcohol dependency and long-term graft and recipient survival

The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.