Long-term Renal Graft Survival Research Articles

Interferon-γ and its response are determinants of antibody-mediated rejection and clinical outcomes in patients after renal transplantation.

Interferon-γ (IFN-γ) is an important cytokine in tissue homeostasis and immune response, while studies about it in antibody-mediated rejection (ABMR) are very limited. This study aims to comprehensively elucidate the role of IFN-γ in ABMR after renal transplantation. In six renal transplantation cohorts, the IFN-γ responses (IFNGR) biological process was consistently top up-regulated in ABMR compared to stable renal function or even T cell-mediated rejection in both allografts and peripheral blood. According to single-cell analysis, IFNGR levels were found to be broadly elevated in most cell types in allografts and peripheral blood with ABMR. In allografts with ABMR, M1 macrophages had the highest IFNGR levels and were heavily infiltrated, while kidney resident M2 macrophages were nearly absent. In peripheral blood, CD14+ monocytes had the top IFNGR level and were significantly increased in ABMR. Immunofluorescence assay showed that levels of IFN-γ and M1 macrophages were sharply elevated in allografts with ABMR than non-rejection. Importantly, the IFNGR level in allografts was identified as a strong risk factor for long-term renal graft survival. Together, this study systematically analyzed multi-omics from thirteen independent cohorts and identified IFN-γ and IFNGR as determinants of ABMR and clinical outcomes in patients after renal transplantation.

Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

Purpose The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.

Clinical Outcomes of Everolimus With Reduced-Dose Tacrolimus vs Mycophenolate Mofetil With Standard-Dose Tacrolimus in De Novo ABO-Incompatible Kidney Transplant Recipients: 1-Year Follow-up

One of the major barriers for long-term renal graft survival is considered to be calcineurin inhibitor nephrotoxicity, contributing to chronic graft dysfunction. Thus, recent immunosuppressive strategies are focused on regimens that can reduce or avoid exposure to calcineurin inhibitors. Herein, we carried out a small-scale pilot study to assess whether everolimus (EVR) with reduced-dose tacrolimus (Tac) is an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant compared with mycophenolate mofetil (MMF) with standard-dose Tac. This retrospective single-center cohort study included patients who underwent ABO-incompatible kidney transplant at our institution between January 2016 and December 2019. Those whose immunosuppressive regimen was changed by reasons other than rejection during the 1-year follow-up period were excluded. A total of 24 patients were enrolled in this study: 10 patients who received an EVR with reduced-dose Tac regimen and 14 patients who received an MMF with standard-dose Tac regimen. Tac trough levels in the EVR group were significantly lower than those in the MMF group (P < .001). No patients died or lost their grafts during the follow-up period. There were no significant differences in renal function, proteinuria, and prevalence of hyperlipidemia between the 2 groups at 1 year after transplant. There were no significant differences in the incidence of rejection (acute cellular rejection, steroid-resistant acute cellular rejection, acute antibody-mediated rejection) and infection (cytomegalovirus viremia, cytomegalovirus disease, BK viremia, BK virus nephropathy) between the 2 groups. Comparable with MMF with standard-dose Tac, EVR with reduced-dose Tac might be an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant.

Effects of bisphosphonates on long-term kidney transplantation outcomes.

Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. Bisphosphonates may improve long-term graft survival in kidney transplant recipients.

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver-Kidney Transplants.

Recipients of simultaneous liver-kidney transplantations (SLKTs) have a lower risk of rejection compared with recipients of kidney transplants alone. However, there is disagreement about the impact of pretransplant anti-human leukocyte antigen sensitization on patient and kidney graft survival in the long term. The aim of the study was to evaluate the impact of the recipient immunological risk and comorbidities in renal graft outcomes on SLKT. We reviewed the SLKTs performed in our center from May 1993 until September 2017. Patient and graft survival were analyzed according to the immunological risk, comorbidities, liver and kidney rejection episodes, immunosuppression, and infections. A total of 20 recipients of SLKT were considered in the high immunological risk (HIR) group, and 68 recipients were included in the low immunological risk (LIR) control group. The prevalence of hepatitis C virus infection, second renal transplant, and time on dialysis prior to transplantation were significantly higher in the HIR group. The incidence of acute kidney rejection was higher in the HIR group (P<0.01). However, death-censored kidney graft survival as well as the estimated glomerular filtration rate at follow-up were not different between the 2 groups. Comorbidities, but not the immunological risk, impact negatively on patient survival. Despite the higher incidence of rejection in the HIR SLKT group, longterm renal function and graft survival were similar to the LIR group.

Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program.

This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1st year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.

Good long-term renal graft survival and low incidence of cardiac pathology in adults after short dialysis period and renal transplantation in early childhood - a cohort study.

Over the past 30years, there has been an improvement in both patient and graft survival after pediatric renal transplantation (RTX). Despite this success, these patients still carry an elevated risk for untimely death, partly through premature aging of the vasculature. The aim of this study was thus to investigate the long-term outcome of individuals with RTX in childhood, as well as to explore the cardiovascular health of these adults more than a decade later. We studied 131 individuals who had undergone a RTX between the years 1979 and 2005. Furthermore, left ventricular hypertrophy (LVH), coronary artery calcifications (CAC), and related metabolic factors were investigated in a cross-sectional study including 52 individuals as part of the initial cohort. The mortality rate (n=131) was 12.2%. The median estimated graft survival was 17.5years (95% CI 13.6-21.3), being significantly better in children transplanted below the age of 5years (18.6 vs. 14.3years, P<0.01) compared with older ones. CAC were found in 9.8% and LVH in 13% of the patients. Those with cardiac calcifications had longer dialysis vintage and higher values of parathyroid hormone (PTH) during dialysis. Left ventricular mass correlated positively with systolic blood pressure, PTH, and phosphate measured at the time of the study.

Association of immunosuppressive agents and cytomegalovirus infection with de novo donor-specific antibody development within 1 year after renal transplantation

The association between immunosuppressive therapy or cytomegalovirus (CMV) infection and detection of de novo donor-specific antibody (dnDSA) at 1 year after transplantation was evaluated. The impact of dnDSA positivity at 1 year after transplantation on long-term death-censored renal graft survival was also evaluated. One hundred and sixty adults receiving living renal allografts were studied. Inclusion criteria were renal graft survival for at least 1 year and a standard regimen of immunosuppressive therapy with tacrolimus, mycophenolate mofetil (MMF), steroids, and basiliximab. DSA were measured retrospectively by the Luminex assay. The coefficient of variation (CV) was calculated and receiver operating characteristic (ROC) analysis was employed to clarify the association of tacrolimus with development of dnDSA. Seven of the 160 patients (4.4%) were positive for dnDSA. The intra-patient minimum trough level of tacrolimus (cutoff value: 3.2 ng/mL) was associated with development of dnDSA. Discontinuation of MMF and treatment of CMV infection were more frequent in patients with dnDSA than in those without dnDSA. In multivariate analysis, a low trough level of tacrolimus, discontinuation of MMF, and treatment of CMV infection within 1 year after transplantation were independently associated with detection of dnDSA at 1 year. In patients with or without dnDSA at 1 year, the 10-year allograft survival rate was 51.4 versus 87.9%, respectively (P = 0.002). A lower tacrolimus trough level, discontinuation of MMF, and treatment of CMV infection were associated with dnDSA positivity. Further investigation is needed to determine whether a new immunosuppressive regimen that avoids these factors can reduce dnDSA positivity.

SAT-095 CLINICAL OUTCOME OF KIDNEY TRANSPLANTATION FROM DECEASED DONORS WITH ACUTE KIDNEY INJURY

There are reports that kidney transplantation (KT) from donors with acute kidney injury (AKI) have similar long-term renal function and graft survival compared with KT from donors without AKI, but there is no established recommendation. Clinicians may hesitate to use the kidney with acute kidney injury due to fear of a poor outcome. This study aimed to investigate the clinical outcome in patients who received kidneys from deceased donors with AKI. From 1998 to 2016, we retrospectively reviewed patients undergone kidney transplantation from deceased donors. We divided donors into two groups of AKI (acute kidney injury) group and non-AKI group. We analyzed delayed graft function, serum creatinine at 1-month after KT, serum creatinine at 1-year after KT, cold ischemic time, donor’s initial and last serum creatinine level, The Kidney Donor Profile Index (KDPI) etc. Of 181 recipients, kidneys from 21 donors with AKI were transplanted into 30 recipients (AKI group). Another 151 recipients received kidneys from donors without AKI (Non-AKI group). Delayed graft function developed more frequently in the AKI group than in the non-AKI group (40% vs 7.28%; P <0.001). Allograft functions at 1-month and 1-year after KT did not differ between the AKI and non-AKI groups(1-month sCr : 1.25 vs 1.30, p=0.469, 1-year sCr: 1.38 vs 1.13, p=0.691). KT from deceased donors with AKI showed comparable outcomes at 1,6 and 12 months despite high rates of delayed graft function. Our clinical outcome suggests that kidneys from donors with AKI are a potential source to expand the donor pool.

A Tale of Two Kidneys: Differences in Graft Survival for Kidneys Allocated to Simultaneous Liver Kidney Transplant Compared with Contralateral Kidney from the Same Donor

Renal graft lifespan in simultaneous liver kidney transplant (SLK) is generally thought to be shorter than in kidney transplant (KT) alone, raising questions about the utility of SLK. This study aims to estimate what the outcomes would be for a kidney allocated to SLK if it were allocated to KT instead. Using United Network for Organ Sharing data, recipients of SLK from 2003 to 2012 were paired with the recipient who received the partner kidney from the same donor in a kidney or kidney pancreas transplant for analysis. The primary outcomes were long-term patient and renal graft survival. This was investigated using modified multivariable Cox regression, which allowed for changes in the hazard ratio (HR) associated with SLK over time (non-proportional hazards), accounted for the paired nature of the study, and adjusted for differences in recipient characteristics. There were 3,721 recipients in each group. Ninety-day mortality was 8.0% for SLK vs 1.9% for KT recipients (p < 0.001). Median unadjusted renal graft survival was 11 years for the SLK group vs 10.5 years for KT (p < 0.001). The baseline adjusted HRs for death and renal graft loss associated with SLK were 3.03 and 2.05. These HRs became equal to 1 at 6.5 years for death and 5 years for renal graft loss. The HRs for death and renal graft loss associated with SLK at 10 years were 0.55 and 0.50. Although kidneys allocated to SLK vs KT demonstrate worse short-term survival, this risk appears to be reversed when follow-up is extended long-term.

Variability of the Mammalian Target of Rapamycin Inhibitors Is Correlated With Long-Term Renal Graft Survival

BackgroundMany studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival. MethodsWe analyzed 279 adult renal transplant patients converted to an mTOR-i. CV was calculated using at least 3 blood trough levels between 3 and 18 months postconversion. ResultsThe mean and median CV of the entire group was 25.54% and 23.7%, respectively. SRL and EVL mean CV was 23.8% and 27.1% (P = .03), respectively. The group of patients into the last tertile with CV> 28.52% presented a lower death-censored graft survival (75.26% vs. 93.01%, P < .0001) with a mean follow-up of 66.5 months. ConclusionThe CV of mTOR-i is correlated with long-term renal graft survival, so it should be considered a prognostic factor. SRL has a lower CV than EVL in renal transplant patients converted to mTOR-i in the stable posttransplant phase.

Metabolic risk profile in kidney transplant candidates and recipients.

Metabolic risk factors of cardiovascular disease such as abnormal glucose regulation, obesity and metabolic syndrome, dyslipidaemia, metabolic bone disease, hyperuricaemia and other less traditional abnormalities are common in both kidney transplant candidates and recipients. In kidney transplant candidates, the presence of these risk factors may impede patient access to transplantation by increasing the risk of developing comorbidities while on the waiting list, prolonging the time to wait-listing and, in some patients, eventually jeopardizing their suitability for kidney transplantation or increasing the risk of severe perioperative complications. In transplant recipients, metabolic risk factors may be associated with increased mortality with a functioning graft and with reduced long-term renal graft survival. Although most transplant recipients have no contraindication to the use of drugs that undergo renal excretion, they may be at risk of drug-to-drug pharmacokinetic interactions with anti-rejection medicines. In this review, we have highlighted the main objectives of evaluating the metabolic abnormalities in transplant candidates and recipients, how this evaluation should be carried out in practice and what currently the most valuable treatment strategies are for modifying the associated risks. We conclude that, for every potential transplant candidate, every effort should be made to control metabolic abnormalities causing arterial calcification, which may impede access to transplantation and impair transplant outcome. In transplant recipients, metabolic abnormalities that result from adverse effects of anti-rejection therapy may be effectively controlled by lifestyle changes and judicious use of drugs for the treatment of abnormal glucose metabolism and dyslipidaemia.

Significance of De novo Donor-Specific Anti-HLA Antibodies in Renal Transplantation: A Single Center Experience

T cell-mediated rejection (TCMR) became controllable, and the long-term renal graft survival came to be obtained by the recent progress and innovation of the immuno-suppressants. Whereas the prophylaxis and control of antibody-mediated rejection (ABMR) caused by donor-specific anti-HLA antibody (DSA) are still insufficient and affect the long-term renal graft survival. DSA was classified roughly as follows: preexisting DSA existed in the patients before renal transplantation (RTx), and de novo DSA produced in the patients after RTx. There are many reports about the effect that preexisting DSA gives to a renal graft, and the treatment for ABMR with preexisting DSA is established to some degree. In contrast to preexisting DSA, it cannot be said that de novo DSA are considered enough at present. In this study, we examined the impact that de novo DSA gave to a renal graft in 40 RTx patients under treatment in our hospital. Although there was no significant difference as to the renal graft function in DSA positive and negative group, the renal graft survival showed the tendency that was better in a DSA negative group than a positive group (85% vs. 55%, P=0.0553). We perform monitoring of the de novo DSA positively and should contribute to the prognosis improvement of the renal graft in future.

Variability of the Estimated Glomerular Filtration Rate in the First Year after Kidney Transplantation Is an Independent Risk Factor for Poor Renal Allograft Outcomes: A Retrospective Cohort Study.

Renal function in the first year after kidney transplantation (KT) can predict long-term renal graft survival. This study investigated whether estimated glomerular filtration rate (eGFR) variability during the first year after KT is a risk factor for poor renal allograft outcomes. This retrospective cohort study included 3077 patients who underwent repeated eGFR measurements for 1 year after KT at Severance Hospital Transplantation Center between 1979 and 2012. The eGFR variability during the first year after KT was the predictor. The patients were divided into four quartile groups of eGFR variability according to the coefficient of variation for eGFR (eGFR-CV). We selected a cutoff of eGFR-CV for graft failure and performed the sensitivity analyses. The graft outcome was worse in the highest quartile group of eGFR variability than in the other groups among all patients (Q4: HR 1.631, 95% CI 1.278–2.081; p < 0.0001) and among patients without AR (Q4: HR 1.425, 95% CI 1.024–1.982; p = 0.0358) after adjusting for eGFR at 1 year after KT and other covariates. Additionally, all-cause mortality was higher in this highest quartile group than in the other groups among all patients but not among patients without AR. Higher eGFR-CVs than the cutoff were significantly associated with a high risk of graft failure among all patients (HR 1.670, 95% CI 1.395–2.000; p < 0.0001) and among patients without AR (HR 1.899, 95% CI 1.457–2.477; p < 0.0001) after fully adjusting for covariates. For all-cause mortality, a higher eGFR-CV was an independent risk factor among all patients but not among patients without AR after adjusting for covariates. eGFR variability in the first year after KT is an independent risk factor for poor renal allograft outcomes.

A case report of recurrent C3 glomerulonephritis 18 months after renal transplantation

The recurrence of glomerulonephritis (GN) is critical to the prognosis of long-term renal transplant graft survival. C3 GN is a rare GN with a poor prognosis, and there are only a few reports of recurrent cases after renal transplantation. We recently experienced a case highly suspected of C3 GN recurrence. The patient was a 67-year-old male who had suffered from end-stage renal disease (ESRD) and started dialysis at the age of 60. His primary renal disease was unknown. At the age of 63, renal transplantation was successfully performed. His serum creatinine (Cr) level was maintained at 1.2 to 1.5 mg/dl, with no urinary protein or occult blood until 18 months after the transplant when urinary occult blood and protein became constant, along with an elevated Cr level at 1.5 to 1.6 mg/dl. The tentative diagnosis following a protocol biopsy at 36 months was dense-deposit disease. However, the pathological findings of an episode biopsy performed 1 year later, when his Cr level elevated to 2.0 mg/dl after varicella zoster virus reactivation, revealed no acute rejection but were compatible with C3 GN. These findings are consistent with a previous report on recurrent C3 GN that revealed relatively rapid loss of graft function, contrasting well with slow progression occurring in the native kidney. This case is possibly the first report in Japan of recurrent C3 GN after renal transplantation.

Adult-sized Renal Transplantation in Small Pediatric Recipients Achieves Long-term Outcomes Comparable to Size-matched Transplantation

Background: The use of adult-sized kidneys seems applicable to low-weight children where size-matched donors are scarce. The aim of this study is to assess the impact of donor-recipient size mismatch on long-term renal graft and patient survival in small recipients, in order to optimize graft allocation. Methods: Between 1999-2010, 46 renal transplants were performed in recipients glomerular filtration rate (GFR), proteinuria, rejection episodes, graft and patient survival were analyzed and compared between groups at the time of transplantation (T0), at one (T1), two (T2), five years (T5), and at the end of the study (TF). Results: The mean renal size (longitudinal length in cm) was significantly different at T0, T1 and T2 between both groups (pT0<0.01; pT1<0.01; pT2<0.01), showing a significant increase in group B during the follow up, being similar to group A at T5 and TF (pT5=0.16; pTF=0.92). The mean GFR (ml/min/1.73 m2) was significantly higher at T0 in group A, compared to B (GFRA=148 ± 47; GFRB=111 ± 33; pT0=0.01); at T1 it decreased in A and increased in B (GFRA=127 ± 38; GFRB=121 ± 31; pT1=0.66), with similar values in both groups at T2, T5 y TF (pT2=0.83; pT5=0.15; pTF=0.90). During follow-up (8.6 ± 4.1 yrs) 9 grafts were lost, 2 in A and 7 in B. Two patients died in group B. No significant differences were observed in graft and patient survival at 5 and 10 years (p=0.66; p=0.19) neither proteinuria nor rejection. Conclusion: Adult-sized grafts in small recipients showed a reduction of the function, but remained a stable size. These grafts can be safely transplanted with comparable outcomes to size-matched kidneys.

Shorter waitlist times and improved graft survivals are observed in patients who accept hepatitis C virus+ renal allografts.

There is a paucity of data regarding long-term renal graft survival in hepatitis C virus positive (HCV+) patients. We analyzed our institution's experience with HCV+ renal transplantation and factors contributing to subsequent renal graft failure. We analyzed 1,679 adult, deceased donor, single-organ renal transplants occurring between 2000 and 2012. Recipient and donor demographics, HCV serostatus, and graft outcome and function were evaluated. Of 1,679 patients, 195 HCV+ recipients (R+) received renal transplants from HCV+ donors (D+), in contrast to 1,418 HCV negative (HCV-) recipients (R-) who received grafts from HCV- donors (D-), and 66 R+ patients who received D- kidneys. Death-censored graft survival in the R+/D+ population was better than graft survival for R+/D- patients, despite R+/D+ patients having higher rates of hypertension and African Americans. Waitlist times for patients accepting HCV+ grafts was 318 days (for R+/D+ patients) versus 613 days (R-/D-) or 570 days (R+/D-). On multivariate analysis, waitlist times were independently predictive of graft failure. R+/D+ patients spent less time on the transplant waitlist, which contributed to improved death censored graft survival when compared with R+/D- patients.

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.

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.