Cause Of Graft Failure Research Articles

In Vivo Imaging of Pancreatic Islet Grafts in Diabetes Treatment.

Transplantation of pancreatic islets has potential to offer life-long blood glucose management in type I diabetes and severe type II diabetes without the need of exogenous insulin administration. However, islet cell therapy suffers from autoimmune and allogeneic rejection as well as non-immune related factors. Non-invasive techniques to monitor and evaluate the fate of cell implants in vivo are essential to understand the underlying causes of graft failure, and hence to improve the precision and efficacy of islet therapy. This review describes how imaging technology has been employed to interrogate the distribution, number or volume, viability, and function of islet implants in vivo. To date, fluorescence imaging, PET, SPECT, BLI, MRI, MPI, and ultrasonography are the many imaging modalities being developed to fulfill this endeavor. We outline here the advantages, limitations, and clinical utility of each particular imaging approach.

Use of Post-transplant Cyclophosphamide Treatment to Build a Tolerance Platform to Prevent Liquid and Solid Organ Allograft Rejection.

Corneal transplantation (CT) is the most frequent type of solid organ transplant (SOT) performed worldwide. Unfortunately, immunological rejection is the primary cause of graft failure for CT and therefore advances in immune regulation to induce tolerance remains an unmet medical need. Recently, our work and others in pre-clinical studies found that cyclophosphamide (Cy) administered after (“post-transplant,” PTCy) hematopoietic stem cell transplantation (HSCT), i.e., liquid transplants is effective for graft vs. host disease prophylaxis and enhances overall survival. Importantly, within the past 10 years, PTCy has been widely adopted for clinical HSCT and the results at many centers have been extremely encouraging. The present studies found that Cy can be effectively employed to prolong the survival of SOT, specifically mouse corneal allografts. The results demonstrated that the timing of PTCy administration is critical for these CT and distinct from the kinetics employed following allogeneic HSCT. PTCy was observed to interfere with neovascularization, a process critically associated with immune rejection of corneal tissue that ensues following the loss of ocular “immune privilege.” PTCy has the potential to delete or directly suppress allo-reactive T cells and treatment here was shown to diminish T cell rejection responses. These PTCy doses were observed to spare significant levels of CD4+ FoxP3+ (Tregs) which were found to be functional and could readily receive stimulating signals leading to their in vivo expansion via TNFRSF25 and CD25 agonists. In total, we posit future studies can take advantage of Cy based platforms to generate combinatorial strategies for long-term tolerance induction.

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany

Penetrating keratoplasty (PK) gets more and more reserved to cases of increasing complexity. In such cases, ocular comorbidities may limit graft survival following PK. A major cause for graft failure is endothelial graft rejection. Suture removal is a known risk factor for graft rejection. Nevertheless, there is no evidence-based regimen for rejection prophylaxis following suture removal. Therefore, a survey of rejection prophylaxis was conducted at 7 German keratoplasty centres. The aim of the study was documentation of the variability of medicinal aftercare following suture removal in Germany. Seven German keratoplasty centres with the highest numbers for PK were selected. The centres were sent a survey consisting of half-open questions. The centres performed a mean of 140 PK in 2018. The return rate was 100%. The findings were tabulated. All centres perform a double-running cross-stitch suture for standard PK, as well as a treatment for rejection prophylaxis with topical steroids after suture removal. There are differences in intensity (1 - 5 times daily) and tapering (2 - 20 weeks) of the topical steroids following suture removal. Two centres additionally use systemic steroids for a few days. Rejection prophylaxis following PK is currently poorly standardised and not evidence-based. All included centres perform medical aftercare following suture removal. It is assumed that different treatment strategies show different cost-benefit ratios. In the face of the diversity, a systematic analysis is required to develop an optimised regimen for all patients.

Predictors of graft outcome in renal transplant recipients with antibody-mediated rejection

Abstract. Active and chronic antibody-mediated rejection (ABMR) is a common cause of graft failure. Prognostic markers of this complication are not well defined. We aimed to find out the demographic, histopathological and clinical characteristics of transplant recipients who developed ABMR and evaluate the impact of these features, and anti-rejection treatment modalities on graft survival. 
 Methods. Thirty-two patients who developed ABMR (22 male; mean age 40.59±12.52 years) were included in this study. Data were evaluated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff's 2013 classification.
 Results. Among the 32 cases, 26 were transplanted from living donors. Mean serum creatinine at the time of biopsy was 1.99 ±0.09 mg/dL. Proteinuria was 1566.06±353.92 mg/day at the time of biopsy. The need for hemodialysis was significantly related with initial creatinine (p = 0.003); creatinine after three months (p < 0.001) and final creatinine (p < 0.001) as well as initial proteinuria (p = 0.005); proteinuria after three months (p < 0.001) and final proteinuria (p < 0.001). 6 cases showed diffuse C4d positivity, 26 cases showed focal c4d positivity. Five of 6 patients with diffuse C4d staining in renal biopsy were hemodialyzed at first and third months despite anti-rejection therapy (p=0.029 and 0.041, respectively).
 Mean survival time was 1654.67±220.40 (95% CI 1222.68-2086.66) days for focal staining C4d cases and 366.16±36.44 (95% CI 294.73-437.60) days for diffuse staining C4d cases. The difference was statistically significant (p=0.012). Two of the patients died, 15 experienced graft loss and 17 survived with functioning grafts. Mean survival time between anti-rejection treatment modalities showed no statistical significance (p=0.15)
 Conclusions. Serum creatinine, proteinuria at the time of biopsy, diffuse peritubular C4d staining were significantly associated with graft survival. Early diagnosis is important to improve success in the treatment of ABMR and graft survival

Clinical Characteristics and Outcomes of Short-term Repeat Corneal Transplantation

ABSTRACT Purpose To explore the primary indications, direct causes and graft survival of short-term repeat keratoplasty. Methods An analytical cross-sectional study. Results The primary indications for keratoplasty were infectious keratitis (67.9%) and immune keratopathy (12.8%). The direct causes of graft failure were infectious ulcer (43.6%) and recurrence (30.8%). Pre-operative hypopyon (P = 0.017, HR = 1.757) and use of decellularized porcine corneas as grafts (P = 0.005, HR = 2.690) were independent risk factors for graft failure. The Kaplan–Meier analysis revealed that the 1-year survival rate of 88 repeat grafts was 85.2%, and the 5-year survival rate was 79.2%. The survival rates of the repeat grafts were significantly higher than those of the first grafts (P < 0.001). Conclusion Infectious keratitis is the most common indication of short-term graft failure and is often failed by infectious ulcer and keratitis recurrence. While the decellularized porcine cornea is a promising application in developing countries, certain difficulties, such as graft melting, remain unresolved.

Detection of cardiac allograft vasculopathy by multi-layer left ventricular longitudinal strain in heart transplant recipients.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse type of coronaropathy that develops in the transplanted human heart, representing a major cause of graft failure and mortality. Nowadays the gold standard for the diagnosis of CAV is coronary angiography (CA). Non-invasive CAV detection, especially in the early stages of the disease, is still challenging. Our study aimed to investigate the role of speckle tracking echocardiography (STE), in particular three-layer STE, in predicting CAV at early stages, and if other traditional echocardiographic, clinical or biochemical parameters could relate to CAV. The study population was composed of a total of 33 heart transplanted patients, divided accordingly to the presence or absence of CAV (12 CAV+ , 22 CAV-). All subjects underwent a complete transthoracic echocardiographic examination on the same day of the CA, and all conventional parameters of myocardial function were obtained, including strain values assessed by STE. Strain values were significantly reduced in presence of CAV, at each myocardial layer but in particular the endocardial-epicardial gradient (-4.15 ± 1.6 vs -1.7 ± 0.4% < .0001) that was also highly predictive of CAV (AUC at ROC curve 0.97). Among diastolic parameters, the E wave deceleration time (DT) and the mean E/e' ratio were strongly positively associated with CAV. In our population, left ventricular global longitudinal strain (GLS), layer-specific GLS and the endocardial-epicardial LS gradient, E wave DT and E/e' ratio were the best independent non-invasive predictors of CAV.

Causes of corneal transplant failure: a multicentric study.

To identify the causes of failure of the different surgical corneal graft techniques: penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). This multicentric retrospective study enrolled a consecutive cohort of patients who had undergone any type of keratoplasty between 2001 and 2016. The clinical data were obtained from the patient's medical records, following ethical guidelines, permissions and data protection. The main outcome measured in the study was the cause of graft failure, defined as any irreversible loss of graft transparency capable of compromising vision. The main causes of graft failure were classified as follows: (A) primary graft failure (PGF), (B) immunological rejection, (C) non-rejection (which includes endothelial decompensation without rejection, IOP elevation/glaucoma, diseases of the ocular surface, recurrence of the primary disease, wound dehiscence/hypotonia and trauma, among others) and (D) specific causes of lamellar keratoplasty failure. A descriptive study of the obtained data was carried out. The distribution of the causes of failure was evaluated according to the type of corneal transplant. Our research included a cohort of 571 keratoplasty failures, of which 509 met the inclusion criteria. The analysis of the causes of the PK failure showed that immunological allograft rejection represented the main cause, with 28.2% of the failures, followed by surface diseases (17.8%) and endothelial decompensation without rejection (17.3%). For the PK re-grafts group, the main cause of failure was immunological allograft rejection (34.0%), followed by diseases of the ocular surface (18.5%). For the DALK group, the failures mainly occurred due to surface diseases such as limbal stem cell insufficiency, infectious keratitis, keratolysis or persistent epithelial defect (37.8%). However, the main reason for failure in the DSAEK group was endothelial decompensation without rejection (31.9%) while primary graft failure was the main cause of failure in the DMEK group (64.1%). The main reason for failure in PK was immunological allograft rejection, both in primary and secondary transplants. The leading causes for failure were diseases of the ocular surface in the DALK population, endothelial decompensation without rejection in DSAEK and primary graft failure in DMEK.

Endovascular treatment of arteriovenous graft dysfunction as a result of graft delamination and fracture

BackgroundGraft thrombosis due to fabric delamination is a rare cause of delayed failure of arteriovenous grafts. Graft delamination is primarily an imaging diagnosis and is confirmed with the help of ultrasound which shows the separation of graft fabric layers. Only two such cases have been described in the literature so far.Case presentationWe present a case of upper extremity arteriovenous graft thrombosis in a 79 year old COVID-19 positive patient with end-stage renal disease. The diagnosis was established on ultrasonography which revealed separation of the graft fabric layers with thrombosis within the “false” and “true” lumen of the graft. The patient was managed with angioplasty and embolectomy of the clot material followed by stent-graft placement across the delaminated portion of the graft. Post-procedural angiography confirmed brisk flow across the graft and patient could successfully have subsequent hemodialysis sessions.ConclusionsIdentification of graft delamination as a cause of graft failure is important as its management differs from other conventional causes since it requires stent-grafts to cover the area of delamination to re-establish flow and salvage the AV graft. The recognition of this phenomenon is essential to provide quality care and successful reuse of the AV graft.Level of evidenceLevel 4, Case Report.

Challenges in the complex management of post-keratoplasty glaucoma.

Glaucoma is a serious complication after corneal transplantation and itself a common cause for graft failure and leading cause of vision loss post-keratoplasty due to corneal endothelial decompensation. Endothelial keratoplasty procedures like Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) may be superior to penetrating keratoplasty (PK) regarding the incidence of elevated intraocular pressure (IOP) and development of glaucoma. There are indications that regardless of the method of keratoplasty, some corneal diseases like pseudophakic bullous keratopathy, corneal perforation, and graft rejection have a higher risk for developing post-keratoplasty glaucoma than keratoconus and corneal dystrophies and likewise respond less to IOP lowering therapy. In this review, the pathophysiology of post-keratoplasty glaucoma, the diagnostic tools with focus on different devices, and their limitations with regard to measuring IOP and the treatment modalities are presented.

Dropless penetrating keratoplasty: immunosuppression by a subconjunctival dexamethasone implant, pilot tolerance and safety study

AbstractPurposePenetrating keratoplasty (PK) remains the first technic of corneal transplantation worldwide and rejection a common cause of graft failure. Its prevention has been based for decades on repeated instillation of steroid eye drops (dexamethasone, prednisolone, rimexolone). Nevertheless, the overall survival of corneal transplants, all indications combined, is lower than that of some organ transplants. Both compliance and the discontinuous nature of the eye drops may be involved. The improvement of immunosuppression could avoid numerous graft failures. In a rabbit model of PK, we previously demonstrated that a subconjunctival dexamethasone implant (Ozurdex) was well tolerated and prevented rejection as efficiently as steroid eye drops trice daily during the first 5‐6 weeks. We then designed a clinical trial to first investigate the tolerance and safety of subconjunctival Ozurdex after PK.MethodsSingle centre, phase II non‐randomized tolerance and safety pilot study on 14 patients (NCT02834260). Designed to analyze the risk of increased intraocular pressure (IOP, primary endpoint at month 1), possible discomfort, resorption time, and collect initial efficacy data. The implant was injected at the 12 o'clock position, 5 mm from the limbus, at the end of PK, in order to deliver dexamethasone immediately. A steroid eye drop relay was planned at the time of complete resorption of the implant. Patients were monitored at regular intervals during 12 months: IOP, discomfort and redness scores, implant status, rejection episode, endothelial cell density, and central corneal thickness by OCT. An independent adverse event committee gave its opinion after the first patient, then at regular intervals.ResultsNo increase in IOP, no adverse event related to the implant was observed. The average duration of resorption was 6 weeks. The therapeutic relay with dexamethasone eye drops was uneventful.ConclusionsHis is the first proof of concept that dropless immunosuppression is possible after penetrating keratoplasty. Ozurdex, chosen here because it was the only ophthalmological steroid implant marketed in France, obviously resorbs too quickly, but this work paves the way for the use of other implants that release a steroid or another immunosuppressive agent in the very long term.

Tectonic Keratoplasty in Patients with Non-traumatic, Non-infectious Corneal Perforations

Introduction:The study aims to report clinical results of tectonic keratoplasty for non-traumatic, non-infectious corneal perforations.Materials and Methods:The medical records of 12 patients who underwent tectonic penetrating keratoplasty between October 2014 and August 2018 at Ege University Ophthalmology Department were retrospectively reviewed.Results:The mean age of the patients was 52.92±30.34 (range, 2-82) years. The causes of corneal perforation were dry eye (neurotrophic keratopathy (n=4), limbal stem cell deficiency (n=2), exposure keratopathy (n=2) and graft versus host disease (n=1)) in 9 patients. In the remaining 3 patients, the etiology of perforation was not determined. The mean Visual Acuity (VA) was 2.98±0.39 (range, 1.8-3.1) LogMAR before the surgery. Despite conservative treatment, tectonic penetrating keratoplasty had to be performed in all patients in order to manage the perforation. Mean time in between initial examination and surgery was 10.75±12.04 (1-41) days. In 2 patients, allogenic limbal stem cell transplantation; in one patient, lateral tarsorrhaphy and in one patient symblepharon release with amniotic membrane transplantation were performed additional to tectonic keratoplasty. Mean follow-up time was 57.88±55.47 (4-141) weeks. Grafts were clear in 6 eyes and opaque in 5 eyes. The main causes of graft failure among opaque grafts were ocular surface disease (3), allograft rejection (1) and glaucoma-related endothelial failure (1). Phthisis bulbi was detected in one patient with congenital glaucoma due to vitreous loss at the time of perforation. The mean final VA in patients who had clear grafts was 1.83±1.03 (range, 0.8-3.1) LogMAR.Conclusion:To prevent serious complications in non-traumatic, non-infectious corneal perforations, providing anatomic integrity immediately is a must. If conservative treatment is inadequate or the perforation area is extensive, tectonic penetrating keratoplasty is indicated. Besides, it is important to manage the etiological risk factors in order to obtain successful clinical follow up.

Total nephroureterocystectomy and urethrectomy due to urothelial carcinoma associated with the BK polyomavirus infection after kidney transplantation: a case report with literature review

BackgroundBK polyomavirus (BKPyV) infection after kidney transplantation is an important cause of graft failure among kidney transplant recipient and may cause malignant tumor, although the association between BKPyV infection and malignant tumor has been controversial yet.Case presentationWe report a case of a 39-year-old-male kidney transplantation (KTx) recipient with urine BKPyV replication who developed a graft pelvic tumor with the positive Simian virus 40 large T antigen (SV40 TAg). The patients received a living-related KTx from his 65-year-old mother. A protocol biopsy at 14 months after KTx showed BKPyV-associated nephropathy. Therefore, the dose of immunosuppressants was reduced, resulting in improved BKPyV viremia, but viruria persisted. About 117 months after KTx, urine cytology showed atypical cells suspicious for malignancy. Cystoscopy revealed a tumor on the neck of the bladder. Transurethral resection of the bladder tumor (TUR-BT) was performed; however, the diagnosis of malignancy was not confirmed at that time. Six months after the TUR-BT, urine cytology showed atypical cells definite for malignancy. Computed tomography and retrograde pyelography showed no evidence of urinary tract tumor and metastasis. Subsequently, total nephroureterocystectomy and urethrectomy were performed. Histological examination of the graft ureter revealed a high-grade urothelial carcinoma, with glandular differentiation, pT1. Immunohistochemically, the tumor showed positivities for SV40 TAg and p53, along with increased Ki67 labeling cells were increased. By contrast, nonneoplastic cells were negative for SV40 TAg. At the time of writing the present manuscript, the patient is free from recurrence or residual tumor and being closely monitored without additional therapy, 32 months after the surgery.ConclusionThe relationship between BKPyV infection after KTx and bladder carcinogenesis remains to be elucidated. However, when the KTx recipients who continue to have BKPyV infection for a long time are treated, the possibility of risk factors for renourinary carcinoma should always be carefully considered.

Five Years Pathological Evaluation of Corneal Regrafts: A Study from Southern Iran.

Purpose Corneal regrafts sometimes needed to restore the transparency after graft failure. The aim of the study is five years epidemiologic and histopathological evaluation of corneal regrafts. Methods In this cross-sectional study, all corneal regrafts during 5 years (2012–2016) were assessed in the Khalili Ophthalmology Center at Shiraz city. Demographic data including age, area of residence, primary disease, type of graft, cause of regraft, interval between primary and subsequent grafts (IPSG), associated eye diseases or surgeries, and systemic diseases were recorded. Also, microscopic findings of corneas were reviewed. Results Among a total of 1190 corneal grafts, 76 of them (6.38%) were regrafts. The most common type of grafting was penetrating keratoplasty (PK). The shortest IPSG was observed in fungal keratitis. Main causes of graft failure were endothelial dysfunction, infection, immunologic rejection, technical problems, and recurrence of primary disease, respectively. The most common histopathological finding in failed grafts was severe endothelial cell loss (89.8%). Also, more than half and one-third of cases had Descemet membrane changes and stromal ingrowth, respectively. Conclusion Endothelial cell loss was the major cause of failure in our study. Also, recurrence rate in infective cases, especially fungal keratitis, was very high. Considerable presence of histopathological changes such as doubling of Descemet membrane and retrocorneal fibrous ingrowth need further investigations. Perhaps, modification in techniques of corneal grafting and assessment of donor tissue and recipient bed along with any need for longer medical treatment are the basis for future studies in order to increase graft survival.

Outcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis.

To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986-2017; to determine the factors that influence survival. Retrospective cohort analysis (registry data). Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986-2017, in all four paediatric and six adult liver transplantation centres in the two countries. Graft and patient survival at one, 5, 10 and 15 years. 142 liver retransplantations were undertaken in children (59 during 1986-2000, 83 during 2001-2017). Kaplan-Meier survival analysis indicated that survival was significantly greater during 2001-2017 than 1986-2000 (P<0.001). During 2001-2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03-1.4 years) during 1986-2000, and 1.8 years (IQR, 0.1-6.8 years) during 2001-2017 (P=0.002). The proportion of graft failures that involved split grafts was larger during 2001-2017 (35 of 83, 42%) than 1986-2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

Treatment Strategies for Antibody-mediated Rejection in Kidney Transplantation and Its Prevention

This article reviews the current treatment strategies of antibody-mediated rejection in kidney transplantation, which is increasingly recognized as the leading immunological cause of graft failure. The pathophysiologic complexity of this condition poses significant challenges for its treatment; however, progress toward advancing our understanding of its pathogenesis and diagnosis will allow for identification of new therapeutic targets. Emphasis is also given to prevention, which is mainly based on careful assessment of the transplant candidate and immunological risk stratification.

Monoclonal gammopathy of undetermined significance coexisting in patients undergoing kidney transplantation does not adversely influence post-graft clinical outcome.

BackgroundManagement of patients with oncohaematological disorders such as monoclonal gammopathy of undetermined significance (MGUS) is a frequent problem in pre-transplant work-up. Insights on disease progression and long-term functional outcomes are still lacking in this setting.MethodsThis was a retrospective analysis on all patients with MGUS who underwent kidney transplant (KT) at our centre between 1 January 2000 and 31 December 2017 (cases, n = 65). Patients were matched with a control group (KTs with similar characteristics but without history of haematological disease, controls, n = 1079). Primary endpoints were graft and patient survival; secondary endpoints were causes of graft failure, patient death, occurrence of allograft rejection, post-transplant neoplasia (not correlated to previous disorder) and/or infectious episodes.ResultsThe MGUS and control groups had a similar mean age [60 (29–79) versus 55.2 (19.3–79.5) years, respectively] and percentage of males (69.2% versus 64.6%, respectively). Median follow-up time since KT was 3.5 years (0–14) in cases and 8.3 years (0–14.9) in controls. All MGUS patients underwent KT following extensive multidiscliplinary investigations. No differences were found between cases and controls regarding patient and graft survival or post-transplant complications except for lower incidence of infections (58.7% versus 69.8%, P = 0.019) and increased use of mTOR inhbitors (30.3% versus 14.7%, P = 0.001) in MGUS. MGUS isotype did not influence graft and patient survival. The absence of difference in patients and graft survival was also confirmed in an adjunctive analysis where MGUS were compared with controls (ratio 1:2) matched for recipient age, gender, number of transplantations and transplant period.ConclusionPatients with MGUS may undergo KT without significantly increased risks of complications, provided that appropriate diagnostic procedures are carefully followed. Multidiscipline-based studies are crucial for establishing well designed pre- and post-transplant protocols for the best management of patients with coexisting MGUS and end-stage renal disease.

Ten-Year Survival of Optical Penetrating Keratoplasty and Risk Factors for Graft Failure in Thai Patients

Objective: To determine long-term graft survival and identify risk factors for secondary graft failure of optical penetrating keratoplasty (PK) in Thai patients. Materials and Methods: A Retrospective study of patients that underwent optical PK at Siriraj Hospital between January 2002 and December 2005 was done. Results: Of 131 eyes, primary graft failure was found in two eyes (1.5%) thus, 129 eyes were recruited. The three most common surgical indications were pseudophakic or aphakic bullous keratopathy (33.3%), corneal scars (post-trauma, post-infection) (20.9%), and regrafts (16.3%). Mean follow-up period was 93.2 months (1 to 183 months). One-year, 2-year, 5-year, and 10-year graft survival rates were 84.5%, 73.2%, 50.2%, and 24.7%, respectively. The leading cause of graft failure was irreversible allograft rejection (62.5%). Most (56.0%) of the first graft rejection happened within one year post-operatively. Graft survival was lower in eyes with regrafts, history of glaucoma, deep corneal vascularization, peripheral anterior synechiae, and occurrence of one or more rejection episodes. Multivariate regression analysis demonstrated that peripheral anterior synechiae and occurrence of one or more rejection episodes were the significant independent risk factors for graft failure. Considering patients with the clear grafts at the last follow-up, the final best-corrected visual acuity was 6/36 or better in 66.7% eyes and 6/18 or better in 31.6% eyes. Comparing to pre-operative vision, patients with the clear grafts at the last follow-up had improved visual outcome in most eyes (82.5%). Conclusion: Ten-year survival and visual outcome of optical PK showed successful outcome, however, the survival rate decreased over time. The significant risk factors for graft failure should be cautiously evaluated before surgery. Keywords: Corneal graft survival, Keratoplasty outcome, Optical penetrating keratoplasty

COMPREHENSIVE ANALYSIS OF 40 YEARS’ EXPERIENCE IN PEDIATRIC KIDNEY TRANSPLANTATION

Background: Pediatric kidney transplantation has been the gold standard for children with end-stage renal disease (ESRD). Changes in pediatric kidney transplant has come a long way in Korea since 1979; from changes in immunosuppressants and induction therapies to indications for transplant in children. This study investigates the longterm outcomes of 40 years of pediatric kidney transplantation at a single center in Korea. Method: Pediatric kidney transplantation performed at a single institution in Korea from 1979 to 2018 was retrospectively reviewed. The patient and graft survivals were analyzed by various patient factors using the Kaplan-meier curve, log rank test, univariate and multivariate Cox-proportion hazard models. Different aspects such as causes of graft failure, recurrence of the primary disease and incidence of malignancy that are unique to pediatric kidney transplant were also analyzed. Results and Discussion: Total of 402 pediatric patients underwent 414 kidney transplantations from 1979 to 2018 with a mean follow up duration of 150.4 months. The overall death censored graft survival and patient survival at 10 years was 76.0% and 96.7% respectively. There was a significant increase in 5 year graft survival over the four decades from 57.1% to 93.0% (p<0.001). In the multivariate analysis, tacrolimus over cyclosporine (p=0.008, HR=0.290, 95%CI 0.115-0.727), mycophenolate mofetil over azathioprine (p=0.011, HR=0.394, 95%CI 0.192-0.809) and retransplant (p=0.005, HR=3.378, 1.449-7.875) were the only significant risk factors that effected graft survival. The single most common cause of ESRD in pediatric kidney recipients was focal segmental glomerulosclerosis (FSGS, 22.8%) followed by reflux nephropathy (13.4%) and renal congenital anomalies (7.7%). Although not significant, the 10 year graft survival was higher in patients with nephronophthisis (NPHP) compared to patients with congenital anomalies(renal dysplasia, hypoplasia and reflux nephropathy) and the group of patients with FSGS, IgA nephropathy and HUS (91.6% vs 83.4% and 70.9%, p=0.068). Recurrence of the primary disease was a significant risk factor among the recipients with FSGS, IgA nephropathy and HUS (p=0.019, HR=2.172, 95%CI 1.134-4.162) and the 10 year graft survival with or without recurrence was 59.9% and 74.7% respectively. Recurrence of primary disease (14.0%) and noncompliance (8.5%) were the third and fourth cause out of 129 graft failures (31.2%) followed by chronic and acute rejection (46.5%, 15.5%). Conclusion: Graft survival has improved over the 40 years of pediatric kidney transplantation at our institution due to changes in immunosuppressants from cyclosporine to tacrolimus and from azathioprine to mycophenolate mofetil over time. However, recurrence of FSGS, IgA nephropathy and HUS effects worse graft survival and both recurrence and noncompliance still remain as one of the crucial causes of graft failure in pediatric kidney transplantation.

KIDNEY TRANSPLANTATION IN PEDIATRIC PATIENTS WITH LOWER URINARY TRACT DYSFUNCTION

Introduction: Approximately 30 % of children with end stage renal disease have lower urinary tract dysfunction which can have deleterious influence on kidney transplantation (KTx). The aim of the study is to present single center long-term outcome of kidney transplantation in pediatric recipients with bladder dysfunction. Material and Method: Between 2000 and 2018 there were 752 KTx performed in our center. Within them there were 545 KTx into normal bladder and 207 KTx in patients with bladder dysfunction (130 KTx into native dysfunctional bladder and 77 KTx into urinary diversion). Surgical complications rate, urinary tract infections rate and graft survival in groups of patients transplanted into normal bladder, dysfunctional bladder and urinary diversion were compared. Results: Surgical complications were higher in group of recipients with dysfunctional bladder and urinary diversion in comparison to recipients with normal bladder (33% vs 28% vs 20%). Urinary tract infecions rate was significantly higher in groups of recipients with dysfunctional bladder and urinary diversion in comparison to recipients with normal bladder (57% vs 59% vs 18%). Graft loss was 18.5 % versus 9 % versus 17.9% in groups of recipients with dysfunctional bladder, urinary diversion, and normal bladder, respectively. The major cause of graft failure in each group was chronic rejection. Conclusions: Kidney transplantation in children with lower urinary tract dysfunction and end-stage renal failure offers good long-term results. Urinary tract infections are the most common complications in these patients. The major cause of graft loss is chronic rejecion.

Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem.

Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.