Long-term Renal Graft Research Articles

Utility of Cancer Screening After Kidney Transplantation.

Introduction and Objectives: Kidney transplant recipients (KTRs) are at higher risk of cancer than general population. In addition, malignancy after kidney transplantation was one of the major causes of death with functioning grafts. Cancer screening, which detects early-stage cancer and allows curative treatment, is considered to be effective in reducing cancer-related mortality and morbidity in KTRs. We examined the incidence of malignancy, survival rate, and the efficacy of cancer screening in our institute. Methods: We investigated malignancies occurring in 732 KTRs receiving regular follow-up with and without cancer screening at Soryukai Inoue Hospital after kidney transplantation between 1993 and 2013 on the basis of medical records. As cancer screening, we performed annually tumor marker tests, urinalysis test, fecal occult blood test, ultrasound scan of thyroid and abdomen, CT scan of the chest, abdomen and pelvis, gastroscopy, mammography and Pap smear. Results: We identified 77 malignancies including patients with multiple primary neoplasms, an overall incidence of 10.5 %. The mean follow-up time was 15.1 ± 8.2 yr. The mean time from transplantation to tumor detection was 11.0 ± 7.6 yr. The cumulative incidence of all cancers was 2.1% at 5 years, 6.5% at 10 years, 12.3% at 20 years, and 17.2% at 25 years. Post-transplant lymphoproliferative disorder represented the most frequent malignancies (19.5 %), followed by renal cell carcinoma (13.0 %), breast cancer (11.7 %), gastric cancer (10.4 %), thyroid cancer (6.5 %) and colon cancer (6.5%). When we investigated overall survival and cancer-specific survival, we observed a significantly improved both survival for the KTRs received cancer screening compared with KTRs received no cancer screening (p<0.01, p<0.05, respectively). Conclusion: The incidence of cancer in recipients after kidney transplantation increased in a time dependent manner and reached to 12.8% at 20 years. Consequently, with long-term renal graft survival now feasible, attention must be paid to detecting malignancy after transplantation. Cancer screening might be effective in reducing cancer-related mortality in our series.

The New Body Mass Index System in Predicting Renal Graft Outcomes

BackgroundObesity has been related to poor renal graft function. The aim of this study was to compare the long-term graft outcomes of living-related kidney recipients regarding donor-to-recipient body mass index (BMI) parameters using the old Quetelet BMI formula and the new Trefethen BMI formula. MethodsFrom November 2002 to November 2010, 62 consecutive living-related kidney transplantations were reviewed retrospectively. Four donor-to-recipient BMI parameters were used: (1) BMI difference by the old formula, (2) BMI difference by the new formula, (3) BMI ratio by the old formula, and (4) BMI ratio by the new formula. Long-term outcomes, including graft survival (GS) and rejection-free graft survival (RFGS) either overall or at 5 years post-transplantation, were analysed according to these parameters. ResultsThe baseline demography was similar among tertiles according to the four BMI parameters tested. Although there is no significant difference in the long-term survivals by the old and new BMI formula, we found that the area under receiver operating characteristic (ROC) curve is larger using the new formula, either by BMI difference (0.584 vs 0.559 in 5-year GS and 0.658 vs 0.636 in 5-year RFGS) or by BMI ratio (0.584 vs 0.561 in 5-year GS and 0.644 vs 0.626 in 5-year RFGS). The same trend was observed in overall survival outcomes. ConclusionThe new Trefethen BMI formula seems to predict long-term renal graft outcomes better than the old Quetelet BMI formula.

Early post-transplant immune monitoring can predict long-term kidney graft survival: Soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies

This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4year graft survival (P=0.009 and P=0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P=0.004 and P=0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P=0.00001), correlated with decreased serum creatinine levels (P=0.01) and associated with improved graft survival (P=0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes.

Donor and Recipient Size Mismatch in Adolescents Undergoing Living-Donor Renal Transplantation Affect Long-Term Graft Survival

Controversies exist in the adult literature regarding the use of kidneys from small donors into larger recipients. Little is known regarding this issue in pediatric kidney transplantation. To assess the impact of donor/recipient size mismatch on long-term renal graft survival in pediatric patients undergoing living-donor renal transplantation. We reviewed the United Network for Organ Sharing database from 1987 to 2010 for adolescent (11-18 years old) patients who underwent primary living-donor renal transplantation. According to donor/recipient body surface area (BSA) ratio, patients were stratified into two categories: BSA ratio <0.9 and ≥0.9. Graft survival rates were compared between these two groups using Kaplan-Meier survival curves and Cox proportional hazards models. Of the 1880 patients identified, 116 (6.2%) had a donor/recipient BSA ratio <0.9 and 1764 (93.8%) had a donor/recipient BSA ratio ≥0.9 group. BSA ratio <0.9 conferred an increased risk of graft loss (adjusted hazard ratio, 1.61; 95% confidence interval, 1.13-2.27; P=0.008). Patients with a donor/recipient BSA ratio ≥0.9 group had a significantly longer graft survival compared with those with a donor/recipient BSA ratio <0.9 after adjustment for donor age and gender, recipient age, gender, ethnicity, cause of renal failure, as well as clinical factors, such as cold and warm ischemia time and HLA mismatch. We conclude that low donor/recipient BSA ratio was associated with an increased risk of graft loss. Appropriate size matching conferred better long-term graft survival in adolescents receiving live-donor kidney transplants.

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.

Long-Term Renal Function of Older Live Kidney Donors at Japanese Single Center

Introduction: In Japan, live kidney transplantation occupied about 85% of all kidney transplantation. Because of the lack of deceased donors and increasing recipient age, the number of older donors is increasing. The Japanese society for clinical renal transplantation recommends to evaluate the adaptation carefully of donors seventy years and older. Material and methods: From 1990 to 2010, a total of 86 nephrectomies in living donors were performed at Japanese Kumamoto Red Cross Hospital. We are able to obtain information on 73 patients of the 86 donors (85%). We assessed the long-term renal outcome and graft survival after kidney donation from older live kidney donors(≥60 years old) compared to younger donors(< 60years). Results: Forty-seven donors were younger than 60 years and twenty-six were 60-years or older. Median follow-up was 5.3 years. Elderly had more hypertention before donation. Body mass index, smoking status and the time since donation were similar among the two groups. Elderly had a lower estimated glomerular filtration rate(eGFR) predonation (86.8±15.7 vs 76.0±8.9 ml/min/1.73m2, p< 0.05), but eGFR at latest was not different. In both groups, eGFR declined about 40% just after nephrectomy, but residual renal function was stable on long term follow-up. 10 donors (13.7%) were observed whose eGFR declined 10% more than that at discharge (7 in younger, 3 in older). The risk factor of impaired renal function after nephrectomy is hypertension which included new onset. Age, sex, smoking status, BMI are not associated with deterionate of renal function. One older donor died of arrhythmia during the follow-up period. There were two donors whose eGFR declined under 30 ml/min/1.73m2. One older donor needed dialysis after 11 years of donation. One younger donor's eGFR declined 22ml/min/1.73m2. Their renel function declined after complications such as heart failure, malignancy. In older donors, there were no complications which required extended hospital stay. Graft survival is similar in both groups. Conclusion: In our survey, donor age didn’t influence deterioration of renal function after nephrectomy. Hypertention is related with decline of eGFR progressively. If we screen carefully, donation of older people is considered to be safe. Regardless of age, careful evaluation and follow-up are important for donor's safety after donation.

Long-Term Renal Function of Older Live Kidney Donors at Japanese Single Center

Introduction: In Japan, live kidney transplantation occupied about 85% of all kidney transplantation. Because of the lack of deceased donors and increasing recipient age, the number of older donors is increasing. The Japanese society for clinical renal transplantation recommends to evaluate the adaptation carefully of donors seventy years and older. Material and methods: From 1990 to 2010, a total of 86 nephrectomies in living donors were performed at Japanese Kumamoto Red Cross Hospital. We are able to obtain information on 73 patients of the 86 donors (85%). We assessed the long-term renal outcome and graft survival after kidney donation from older live kidney donors(≥60 years old) compared to younger donors(< 60years). Results: Forty-seven donors were younger than 60 years and twenty-six were 60-years or older. Median follow-up was 5.3 years. Elderly had more hypertention before donation. Body mass index, smoking status and the time since donation were similar among the two groups. Elderly had a lower estimated glomerular filtration rate(eGFR) predonation (86.8±15.7 vs 76.0±8.9 ml/min/1.73m2, p< 0.05), but eGFR at latest was not different. In both groups, eGFR declined about 40% just after nephrectomy, but residual renal function was stable on long term follow-up. 10 donors (13.7%) were observed whose eGFR declined 10% more than that at discharge (7 in younger, 3 in older). The risk factor of impaired renal function after nephrectomy is hypertension which included new onset. Age, sex, smoking status, BMI are not associated with deterionate of renal function. One older donor died of arrhythmia during the follow-up period. There were two donors whose eGFR declined under 30 ml/min/1.73 m2. One older donor needed dialysis after 11 years of donation. One younger donor's eGFR declined 22ml/min/1.73 m2. Their renel function declined after complications such as heart failure, malignancy. In older donors, there were no complications which required extended hospital stay. Graft survival is similar in both groups. Conclusion: In our survey, donor age didn't influence deterioration of renal function after nephrectomy. Hypertention is related with decline of eGFR progressively. If we screen carefully, donation of older people is considered to be safe. Regardless of age, careful evaluation and follow-up are important for donor's safety after donation.

Immunomodulatory Properties of Mesenchymal Stem Cells Combined with Mycophenolate Mofetil Induce T Cell Regulation and Prolong Renal Allografts Survival in Cynomolgus Monkeys

The induction of tolerance to allografts is one of the major goals in transplantation. Mesenchymal stem cells (MSCs) have been shown to be potent immunomodulatory and immunosuppressive properties in vitro and in vivo. However, to the clinical perspective of MSC-based cell therapy, it has not been clearly defined whether immunosuppressants currently utilized in the clinic may affect immunomodulatory capacities of MSCs. The aim of this study was to investigate the effect of combination therapies of MSCs and mycophenolate mofetil (MMF) on delaying acute rejection of renal allografts in Cynomolgus monkey model. MSCs were isolated from born marrow of Cynomolgus monkey. They were expanded and characterized by morphology, phenotypes and immunosuppressive functions. They were positive for CD90, CD73, CD29, CD105, and negative for CD45, CD34 and MHC-II. Monkeys received adoptive multiple infusions of autogeneic MSCs with a short-term and low-dose of MMF achieved long-term renal graft survival (>90 days post-transplantation) with normal serum creatinine (sCr) concentration and ultrasound imaging of transplanted kidney grafts. Confocal fluorescence microscopy analyses revealed that the transplanted PKH-26 labeled MSCs were found in renal allograft, spleen and lymph nodes of the recipients after the transplantation. The monkeys received MSCs showed high frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs). An increased population of interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells and T helper (Th) 2-dominant cytokine shift were detected in survival recipients. Immunosuppressive effect of MSCs was not only showed in CD4+ and CD8+ cells, but also in their subsets of CD4+CD28+CD95- and CD8+CD28+CD95-naïve T cells. A depression in the percentages of CD4+CD28-CD95+ and CD8+CD28-CD95+ effecter memory T cells was observed in MSC treated recipients at the early stage of the treatment. In conclusion, this study shows synergistic effects of MSCs with short-term and low-dose MMF regimen in promoting renal allograft survival in Cynomolgus monkeys, also provides information to motivate the development of MSC therapy strategies in clinical transplantation.

Impact of Urinary Tract Infections and Cytomegalovirus Infections on Long-Term Renal Graft Function

Background: Infections still frequently complicate renal transplantation. Urinary tract infections (UTI) and cytomegalovirus infections (CMV) are supposed to be their most common clinical form in renal transplant recipients. The influence of UTI on graft function appears to be controversial. Methods: A group of 159 renal transplant recipients was analyzed. Creatinine level during the first 24 months post-transplant was followed. Trends in creatinine level as well as eGFR 24 months post-transplant in groups with and without UTI and CMV were compared. Groups were furthermore differentiated with age, sex and the number of episodes. Linear regression models were used to evaluate the trends in creatinine level, Cocroft-Gault formula was used to estimate GFR. The scores in particular subgroups were analyzed with t-Student test. Results: The increasing creatinine level was observed in group with at least one UTI or CMV episode which was positively correlated to the trend in patients with recurrent UTI's and negatively to the trend in patients without infections. Increasing creatinine level was observed in recipients with at least one UTI episode, younger than median for the analyzed group (< 43) in comparison to older recipients (>44) with at least one UTI episode. Stable creatinine level was observed in women with at least one UTI episode by the opposite to decreasing creatinine level in women without infections. Lower eGFR scores 24 months post-transplant were observed in patients with recurrent infections and women with at least one UTI/CMV episode in comparison to the patients without infections in general as well as to men and women separately. Conclusions: Regarding infectious complications, worse graft function parameters were related to recurrent infections, female sex and younger age of the recipients analyzed in the study.

Posttransplant Major Histocompatibility Complex Class I Chain-Related Gene A Antibodies and Long-Term Graft Outcomes in a Multicenter Cohort of 779 Kidney Transplant Recipients

The impact of major histocompatibility class I chain-related A (MICA) antibodies on renal graft outcomes is unclear. The goal of this work was to assess the impact of posttransplant MICA antibodies, assayed at 1 year, with two commercially available kits, on long-term renal graft outcomes. We retrospectively tested sera from 779 kidney transplant recipients with two single-antigen flow bead assays 1 year after transplantation. Samples were considered positive for MICA if they were positive in both tests or positive for MICA specificities that were present in one kit only. The main outcome was 4-year death-censored graft survival. The prevalence of MICA antibodies was 5.4% at 1 year. MICA+ patients were more frequently human leukocyte antigen (HLA) sensitized and regrafted. Four-year death-censored graft survival was not different between MICA+ and MICA- patients (97% vs. 94%, P=0.28). By Cox multivariate analysis, independent risk factors for graft loss were as follows: number of HLA DR mismatches, acute rejection within the first year posttransplantation, 1-year serum creatinine, and the presence of HLA antibodies at 1 year, but not the presence of MICA antibodies. These data do not support an independent pathogenic role for MICA in long-term renal graft injury and question the interest of posttransplant monitoring of MICA antibodies with single-antigen flow bead assays currently available.

PP106. Risk of long term renal graft loss after pregnancy in renal transplant recipients immunosuppressed with calcineurin inhibitors

IntroductionIntron long-term graft function are uncertain. Although there have been a large number of successful pregnancies in renal graft recipients, the effects of pregnancy and type of immunosuppressant drugs. ObjectivesTo analyze (1) the impact of pregnancy on the long term renal function and graft survival of kidney transplant recipients (KTx), and (2) the impact og the pregnancy in (KTx) immunosupressed with calcineurin inhibitors (CNI). MethodsRetrospective analysis of two cohorts: one (PG) formed by all the KTx recipients from our institution that became pregnant between 1973 and 2004, and the other one (NPG) formed by, when possible, up two KTx patients of similar demographic and clinical characteristics: patient age, donor source, donor age, interval between KTx and pregnancy (or a matched interval for NPG), baseline renal function before pregnancy, hypertension, proteinuria >1g, and CNI-based immunosuppression. but without pregnancies. Particular attention has been paid to long-term (5 and 10years) renal function and graft survival. Males were selected to complete NPG if no matched women were available. Statistical analysisAssessment of baseline homogeneity between the two cohorts was performed by appropriate analysis. Time of survival of kidney was estimated by means Kaplan–Meier method and the Cox proportional hazard model was used to perform adjusted analysis. ResultsFifty five pregnancies in 43 patients (PG) and 68 paired controls (NPG) were included in the study. The basal and functional characteristics of PG before pregnancy and NPG were not statistical and clinical significantly different. In a univariate Cox regression analysis, 10 years graft survival after pregnancy/study entry was significantly better in CG (79.9%) than PG (60.9%) (P=0.02). Multivariate analysis of graft survival showed an increased risk of long-term graft loss in pregnant women that had been treated with CNI as immunosuppressant drug compared with NP KTx that received CNIs (HR: 2.4, 95% CI, 1.17–5.00; P=0.02). In a stratified analysis, evaluating separately the recipients that had received or not CNIs, the risk of graft loss was only increased among recipients that became pregnant post-transplantation treated with CNI compared with recipients that had received CNIs but had not become pregnant (HR: 3.3, 95% CI, 1.42–7.45; P=0.005), but not among recipients that became pregnant post-transplantation and received other immunosuppressant agents (HR: 0.9, 95% CI, 0.24–3.80; P=0.94). ConclusionPregnancy in women receiving baseline immunosuppression with CNI significantly increases the risk of long-term graft loss, non observed in KTx patients treated with CNI that not became pregnant, nor in KTx patients that became pregnant but are treated with other immunosuppressant drugs . At our knowledge, this observation has not been previously reported

Detection of Antibodies Against Major Histocompatibility Complex Class I-Related Chain A in Long-term Renal Graft Recipients

To determine the prevalence, allele specificity, and intensity of anti-MICA antibodies in long-term renal graft recipients and to investigate their association with impaired renal function. Sixty-eight long-term (> 10 y) renal graft recipients were divided into 2 groups: (1) patients with impaired renal function (serum creatinine ≥ 2 mg/dL, n=6); (2) patients with normal renal function (serum creatinine < 176.8 μmol/L, n=62). Anti-MICA antibodies were tested using Luminex single antigen beads assays and the frequency, specificity, and intensity of these antibodies were compared between 2 patient groups. MICA antibodies were detected in 33% of impaired renal function patients and 15% of normal renal function patients (P > .05). Anti-MICA*027 antibodies were found in 11.76% of patients, whereas antibody to MICA*012 was found in 2.94% of patients. Interestingly, among all antibody specificities, MICA*001,*004, *007, *009, *012, and *018 were found more frequently in impaired renal function patients than in normal renal function patients. The peak mean fluorescence intensity levels of MICA antibodies in impaired renal function patients were significantly higher than those in normal renal function patients (P < .05). Our data suggest that increased prevalence and intensity of anti-MICA antibodies are associated with impaired renal graft function in long-term renal graft recipients and some MICA antibodies might be more important than others in mediating graft rejection.

Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined. This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR. The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m(2), P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group. This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.

Urinary Tract Infections in Renal Transplant Recipients

Introduction Urinary tract infections (UTIs) are most common infections in renal transplant recipients and are considered a potential risk factor for poorer graft outcomes. Aim To evaluate incidence, clinical manifestations, microbiology, risk factors for UTIs, and the influence of UTIs on long-term renal graft function. Patients and methods We analyzed urine cultures with reference to clinical data of patients who received a renal transplantation from January to December 2009 with a 12-month follow-up. Results The 1170 urine cultures were correlated with clinical data from 89 renal transplant recipients, including 58.4% males and on overall mean age of 48 ± 14 years. The 151 episodes in 49 patients consisted of asymptomatic bacteriuria (65%, n = 98); lower UTIs (13%, n = 19); and upper UTIs (22%, n = 34), as well as five cases of bacteremia. Nearly 48% of UTIs were diagnosed during the first month posttransplantation. The most frequently isolated uropathogens were Enterococcus faecium (33%, n = 24) and Escherichia coli (31%, n = 23). Beginning from the second month, most frequently found bacterium in urine cultures was E coli (65% n = 51). Risk factors for posttransplant UTIs were female gender and a history of an acute rejection episode and/or a cytomegalovirus (CMV) infection. All patients with vesicoureteral reflux of strictures at the ureterovesical junction suffered recurrent UTIs ( n = 7). The evolution of renal graft function did not differ significantly between patients with versus without UTIs. Conclusions UTIs a frequent problem after kidney transplantation most commonly exist as asymptomatic bacteriuria. E coli and E faecium are ther predominant pathogens. Exposure to intensified immunosuppression due to acute rejection episodes or CMV infections represents a risk factor for UTIs. Vesicoureteral reflux or strictures at the ureterovesical junction are risk factors for recurrent UTIs. UTIs did not impair 1-year graft function.

Clinical application of mTORi based immunosuppression for renal transplantation in India

Long-term renal graft survival is hampered by allograft dysfunction and cardiovascular disease resulting from calcineurin inhibitors (CNIs). This has led to the development of immunosuppressive regimens involving mammalian target of rapamaycin (mTOR) inhibitors, sirolimus and everolimus. They seem to provide long-term benefits for kidney function in transplant patients because of their anti-proliferation and anti-tumor properties and absence of nephrotoxicity. Their use has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity associated with CNIs. Both proactive and reactive strategies have been used. Whether existing strategies of using mTORi in renal transplantation is applicable for Indian patient's remains to be seen. Data on side effect profile, economic viability and the impact of these drugs on infections, particularly in India, are worth documenting. After briefly reviewing available data from India, this article explores the indications, patient populations; timing and practical aspects as well as the safety and efficacy of mTORi-based regimens for renal transplantation and suggests a framework which could allow transplant physicians to tailor its use to their own practice with particular reference to the Indian subcontinent.

Predisposing Factors to the Development of Urinary Tract Infections in Renal Transplant Recipients and the Impact on the Long-Term Graft function

Urinary tract infections (UTIs) represent the most common cause of bacterial infection in renal allograft recipients. The purpose of this study was to estimate the predisposing factors and the impact of UTIs in the long-term graft function. We studied 122 patients (75 males and 47 females), aged 44 ± 12 years. UTIs occurring during the first month, during the first year, and through the entire follow-up period were analyzed. Diabetes mellitus (DM), delayed graft function, acute rejection episodes, and urinary tract obstruction were evaluated as potential predisposing factors. UTI episodes (n = 316) were recorded in 74 of 122 patients (60.7%). The most common pathogen was Escherichia coli. Most patients (81%) who developed infection during the first month had a new episode in the first year. Hospitalization was necessary in 141 of the 316 UTI episodes whereas 87 were hospital acquired. A strong correlation between female gender and UTI occurrence was found (p = 0.01). Urinary tract obstruction was also related to the UTI occurrence during the first year after transplantation (p = 0.001). Patients’ age, DM, delayed graft function, and acute rejection episodes did not correlate with UTI. Long-term renal graft function was not found to be affected by UTI occurrence. UTIs are common infectious complications in renal transplant recipients and often relapse and require hospitalization. The long-term graft function is not affected by the occurrence of UTIs.

Utilisation de nouvelles molécules immunosuppres-sives non néphrotoxiques en transplantation rénale, en particulier après lésions d’ischémie-reperfusion

Medium- and long-term renal graft survival depends on 4 main factors: the quality of the harvested graft, ischemia-reperfusion injury during harvesting and re-implantation, rejection, and the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients. The renal tubular and vascular toxicity of anticalcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury. Attention is turning to "old " molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing. Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3. Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a Jak inhibitor.

Extracorporeal Support: Improves Donor Renal Graft Function After Cardiac Death

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4-6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min +/- 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min +/- 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h +/- 1.7). DCD-30 had lower CrCl (0.9 mL/min +/- 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.

Optimal body mass index that can predict long‐term graft outcome in Asian renal transplant recipients

There is limited data concerning the impact of recipient body mass index (BMI) on graft outcome in Asian renal transplant recipients. The aim of this study is to identify whether obesity (BMI > or =25 kg/m(2)) and overweight (BMI > or =23 kg/m(2)) can predict graft outcome. This is a single-centre retrospective study. All patients who received kidney transplantation between 1997 and 2005 were recruited. Patients were categorized according to two different designated BMI cut-off values. One hundred and thirty-one patients were recruited with a median follow-up duration of 73 months. If a BMI cut-off value of 25 kg/m(2) was used, 86.3% patients were classified as non-obese and 13.7% as obese. Obesity was significantly associated with poor renal graft function and decreased patient and graft survival. On the other hand, 34.3% patients were classified as overweight and 65.7% patients as normal if a BMI cut-off value of 23 kg/m(2) was used. Overweight was significantly associated with a lower glomerular filtration rate only. Cox regression analysis showed that obesity (odds ratio (OR) = 3.09), acute rejection (OR = 5.68), pre-transplant diabetes mellitus (OR = 3.21) and age of recipient (OR = 1.06) were all significant independent risk factors associated with graft failure. Recipient BMI > or =25 kg/m(2) is a significant predictive factor for long-term renal graft outcome in the Asian population.

Post‐transplant lymphoproliferative disorder following renal transplantation: A single‐center experience over 40 years

To investigate post-transplant lymphoproliferative disorder (PTLD) following renal transplantation at our institution. Medical records of 631 patients who underwent renal transplantation at Osaka University Hospital between March 1965 and December 2008 were reviewed. PTLD following renal transplantation was detected in 10 patients (five men, five women; mean age at transplantation, 38.5 years). Mean duration from renal transplantation to the onset of PTLD was 7.1 years (range, 5 months to 18 years, 9 months). Mean duration of observation was 3.9 years from the onset of PTLD. Immunosuppressant therapy comprised multidrug combination therapy, including cyclosporine in six patients and tacrolimus in four patients. In addition to a reduction in the immunosuppressant dose, which was performed in all patients, PTLD was treated with surgery in seven patients, radiotherapy in two patients, rituximab in five patients, and cytotoxic chemotherapy in four patients. A complete remission in eight patients and progressive disease in two were observed. At last follow up, seven patients were alive and five patients had functioning grafts. The incidence of PTLD following renal transplantation at our institution is 1.6% with onset occurring more than 5 years after transplantation in five patients. Consequently, with long-term renal graft survival now feasible, attention must be paid to detecting late-onset PTLD.