Risk Factors for Graft Failure and Death following Geriatric Renal Transplantation.
ABSTRACT: BACKGROUND:Population aging is a major health concern in Asian countries and it has affected the age distribution of patients with end-stage renal disease (ESRD). As a consequence, the need for kidney transplantation in the geriatric population has increased, but the shortage of donors is an obstacle for geriatric renal transplantation. The aim of this study was to evaluate risk factors for graft failure and death in geriatric renal transplantation. METHODS:Kidney transplantations performed in a tertiary hospital in South Korea from May 1995 to December 2014 were retrospectively reviewed. Recipients younger than 60 years of age or who underwent other organ transplantations were excluded. The Kaplan-Meier method was used to assess patient and graft survival. A Cox regression analysis was used to evaluate risk factors for graft failure and patient death. RESULTS:A total of 229 kidney transplantation patients were included. Graft survival at 1, 5, and 10 years were 93.2%, 82.9%, and 61.2% respectively. Patient survival at 1, 5, and 10 years were 94.6%, 86.9%, and 68.8%, respectively. According to the Cox multivariate analysis, ABO incompatibility (hazard ratio [HR] 3.91, p < 0.002), DGF (HR 3.544, p < 0.004), CMV infection (HR 2.244, p < 0.011), and HBV infection (HR 6.349, p < 0.015) were independent risk factors for graft survival. Recipient age (HR 1.128, p < 0.024), ABO incompatibility (HR 3.014, p < 0.025), CMV infection (HR 2.532, p < 0.010), and the number of HLA mismatches (HR 1.425, p < 0.007) were independent risk factors for patient death. CONCLUSION:Kidney transplantation in the geriatric population showed good clinical outcomes. ABO incompatibility, DGF, CMV infection, and HBV infection were risk factors for graft failure and the recipient age, ABO incompatibility, CMV infection, and the number of HLA mismatches were risk factors for patient death in geriatric renal transplantation.
Project description:The association of delayed graft function (DGF) and biopsy proven acute rejection (BPAR) of renal allografts is controversial. Borderline rejections comprise a major portion of biopsy results but the significance of such histologic changes is debated. The present study explores the impact of DGF on BPAR with a special emphasis on discriminating the effects of borderline rejection.Single center analysis of 417 deceased donor kidney recipients (age>18; transplantation date 1/2008-2/2015). Patients with primary non-function were excluded. DGF was defined as the need for dialysis within the first week after transplantation. Acute rejection was defined according to Banff criteria. Cox proportional hazards models were used to examine the relationship of DGF with BPAR within the first year.No graft loss was observed during the first year after transplantation. DGF significantly associated with BPAR in the first year, irrespective of whether borderline rejections were included (HR 1.71, 95%CI 1.16,2.53) or excluded (HR 1.79, 95%CI 1.13,2.84).DGF is significantly associated with rejection-with or without borderline changes-within the first year.
Project description:A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II-IV acute graft-versus-host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22-4.66; P=0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft-versus-host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft-versus-host disease rates (HR 2.03; 95% CI: 1.00-4.10; P=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 - 3.18; P=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation.
Project description:OBJECTIVES:Duration of delayed graft function (DGF) and length of hospital stay (LOS) are outcomes of interest in an era that warrants increased efficacy of transplant care whereas renal allografts originate increasingly from marginal donors. While earlier studies investigate the predictive capability of a single renal scintigraphy, this study focuses on the value for both DGF duration and LOS of consecutively performed scintigraphies. METHODS:From 2011 to 2014, renal transplant recipients referred for a Tc-99m MAG3 renal scintigraphy were included in a single-center retrospective study. Primary endpoints were DGF duration and LOS. Both the first (??3 days) and second scintigraphies (3-7 days after transplantation) were analyzed using a 4-grade qualitative scale and quantitative indices (TFS, cTER, MUC10, average upslope). RESULTS:We evaluated 200 first and 108 (54%) consecutively performed scintigraphies. The Kaplan-Meier curves for DGF duration and qualitative grading of the first and second scintigraphy showed significant differences between the grades (p?<?0.01). The Kaplan-Meier curve for the delta grades between these procedures (lower, equal, or higher grade) did not show significant differences (p?=?0.18). Multivariate analysis showed a significant association between the qualitative grades, from the first and second scintigraphy, and DGF duration, HR 1.8 (1.4-2.2, p?<?0.01) and 2.8 (1.8-4.3, p?<?0.01), respectively. CONCLUSIONS:Qualitative grades of single renal scintigraphies, performed within 7 days after transplantation, can be used to make a reliable image-guided decision on the need for dialysis and to predict LOS. A consecutive renal scintigraphy, however, did not show an additional value in the assessment of DGF. KEY POINTS:• Post-transplant renal scintigraphy procedures provide information to predict delayed graft function duration and length of hospital stay. • Performing two consecutive renal scintigraphy procedures within 1 week after transplantation does not strengthen the prediction of delayed graft function duration and length of hospital stay. • Single renal scintigraphy procedures can be used to provide clinicians and patients with a reliable indication of the need for dialysis after transplantation and the expected duration of hospitalization.
Project description:NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury. However, the role of NLRP3 in human renal disease is completely unknown. From a retrospective cohort study, we determined in 1271 matching donor and recipient samples if several NLRP3 single nucelotide polymorphisms (SNPs) were associated with primary non-function (PNF), delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and death-censored graft and patient survival. NLRP3 gain-of-function SNP (rs35829419) in donors was associated with an increased risk of BPAR while NLRP3 loss-of-function SNP (rs6672995) in the recipient was associated with a decreased risk of BPAR in the first year following renal transplantation (HR 1.91, 95% CI 1.38-2.64, P?<?0.001 and HR 0.73, 95% CI 0.55-0.97, P?=?0.03 resp.). NLRP3 SNPs in both donor and recipient were not associated with PNF, DGF, graft survival or patient survival. We conclude that genetic variants in the NLRP3 gene affect the risk of acute rejection following kidney transplantation.
Project description:To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection.Multi-center prospective, double-masked, clinical trial.ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects.ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases.In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.
Project description:BACKGROUND:Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. METHODS:The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg-1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n =?648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). DISCUSSION:Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.
Project description:Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P?<?0.001) and cases of deceased donor transplantation (P?<?0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P?=?0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.
Project description:ABO-incompatible (ABOi) and positive crossmatch (XM) kidney transplantation (KT) have been considered immunologically challenging. The present study analyzed the clinical outcomes in XM positive KT based on ABO incompatibility. We used data from the Korea Organ Transplantation Registry, a nationwide database, and a single-center registry. A total of 263 patients with positive XM were divided into an ABO compatible (ABOc) & XM positive (ABOc/XM+, n?=?176) group and an ABOi & XM positive (ABOi/XM+, n?=?87) group. The overall rejection rate one year after KT was significantly higher in the ABOi/XM+ group than in the ABOc/XM+ group (P?<?0.01). A total of four mortalities occurred, all in the ABOi/XM+ patients (P?<?0.01). There were no differences in surgical complications or the occurrence of infection-related complications, including BK virus nephropathy. Multivariate analysis indicated that female vs. male (odds ratio (OR), 2.27; P?=?0.03), DSA class I (MFI/1000) (OR, 1.10; P?=?0.03), DSA class II (MFI/1000) (OR, 1.10; P?<?0.01), and ABOi & XM+ status (OR, 2.38; P?<?0.01) were significant risk factors for acute rejection during the year after transplantation. Overall graft survival was inferior in ABOi/XM+ patients than in ABOc/XM+ patients (P?=?0.02). ABO incompatibility in XM-positive KT patients was found to be a significant risk factor for the development of rejection within one year after transplantation as well as for long-term graft survival. The anti-blood group A, B and anti-HLA antibodies may show synergistic activity.
Project description:The role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear.Linking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively.Patients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected.Higher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.
Project description:BACKGROUND:Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. METHODS:Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. RESULTS:Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient's biopsy sample. CONCLUSIONS:Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020 . Registered on June 29 2015.