Cause Of Graft Research Articles

#3077 Activity and chronicity index as graft lost predictors in kidney transplant with antibody mediated rejection or isolated microvascular inflammation

Abstract Background and Aims Antibody mediated rejection (ABMR) is the major cause of graft lost in kidney transplant (KT) recipients. Banff classification considers active ABMR (aABMR) and chronic active ABMR (caAMBR) but does not consider isolated microvascular inflammation (iMVI). Considering histologic lesions in kidney biopsies (KB), activity (AI) and chronicity index (CI) have been developed. Only CI ≥4 has been associated to worse graft survival in ABMR, yet the prognostic value of AI and CI in iMVI is still unknown. Our aim was to evaluate chronicity and activity index as prognostic tools in ABMR and iMVI. Method Retrospective study of KT recipients (1987-2022) with KB (2013-2022) with ABMR (category 3, Banff’2019) [group 1] and iMVI [group 2]. We evaluated AI ([glomerulitis (g) + peritubular capillaritis (ptc), arteritis (v) + C4dscore] e CI ([interstitial fibrosis (ci), tubular atrophy (ct), chronic vasculopathy (cv), and 2xchronic glomerulopathy (2cg) scores)]). Our aim was to evaluate chronicity and activity index as prognostic tools in ABMR and iMVI. Results One hundred thirty-nine KT with aABMR (n=48) and caABMR (n=46) (group 1) and MVIi (n=45) (group 2). Graft loss along time of follow-up (35 [15-69] months) was higher in group 1 (41.5% vs 22.2%; p=0.02). AI was higher in group 1 (4 [3-4.5] vs. 2 [2-4]; p<0.001) and CI similar in both groups (4 [3-7] vs. 4 [4-6]; p=0.7). In the multivariate analysis CI (per unit increase) with HR 1.24 [1.09-1.42; p=0.001] and IA ≥4 in ABMR with HR 2.23 [1.08-4.58; p=0.029]. Death-censored graft survival was worse in IA. IA≥ 4 e IC ≥4 La supervivencia del injerto muerte-censurada fue peor en el grupo RH con IA≥ 4 e IC ≥4 (Fig. 1). Conclusion Our findings suggest that the activity index in ABMR and the chronicity index both in ABMR and iMVI are valuable prognostic tools.

#6011 VIRAL INFECTION AND DE NOVO PRODUCTION OF DONOR SPECIFIC ANTIBODIES IN KIDNEY TRANSPLANTATION: DCD VS DBD

Abstract Background and Aims Viruses are among the most common causes of opportunistic infection after transplantation and an accurate screening and follow-up is needed in order to prevent related complication as systemic damages and worsening of kidney function. On the other hand, in the first years after transplantation, antibody-mediated rejection (ABMR) is one of the first cause of graft lost and de novo production of donor specific antibody (dnDSAs) is the main source. In this monocentric study we analysed data of 255 patient transplanted from January 2016 to February 2022. We studied the incidence of viral infection and dnDSAs in the first one year after transplantation in different sub-groups of patients. Method Data was obtained from our monocentric registry, from January 2016 to February 2022. Starting from 299 kidney transplantation we obtained 255 patients with a complete annual follow-up for viral infection and DSA monitoring. We compared the incidence of viral infection and dnDSAs in different sub-group: transplanted from donation after brain-death treated with Basiliximab as induction therapy (DBDb), transplanted from donation after brain-death treated with rabbit anti-human thymocyte immunoglobulin (rATG) as induction therapy (DBDt), transplanted from donation after circulatory death treated with rATG as induction therapy (DCD) and transplanted treated with rATG as induction (DBDt+DCD). Results Global incidence of viral infection was 73% and dnDSAs formation was present in 12,5% of all patients. DBDs showed an incidence of 69% of viral infection and 10% of dnDSAs while in DBDt these values were 77,4% and 25%, respectively. In DCD data of viral infection was higher (96,7%) whereas dnDSAs was 14%. rATG (DBDt+DCD) displayed 87,1% of viral infection and 19% of dnDSAs. Conclusion Viral infection and dsDNAs are two paramount aspects in kidney transplantation and demonstrate different incidences depending on donation profile and immunosuppressive induction therapy. Specifically rATG seems to be associated to an higher rate of viral infection and DCD is the more relevant sub-group. Furthermore, rATG was associated with higher dsDNAs rate, especially in DBD treated with rATG. On the best of our knowledge, this data was never observed before. These data, due to the low number of cases, need to be confirmed from larger cohorts. Moreover our study underlines how significant is to develop a personalized approach in order to reduce complications associated to immunosuppressive therapies.

Venous outflow obstruction in pediatric left lateral segment split liver transplantation.

Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end-to-side triangular venous anastomosis. We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end-to-side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p=.04), re-transplantation (p=.008), and presence of two hepatic veins (p<.0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p=.87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22-8.46; p=.01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. VOO after LLS split LT with end-to-side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re-transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases.

Assessment of the Effectiveness of Patient Education and Interviews in Improving Medication Adherence of Renal Transplant Recipients.

Background Non-compliance with immunosuppressive drugs has been reported as the most significant cause of graft loss.Since non-compliance with immunosuppressive drugs is preventable, certain approaches based on the risk factors and causes of non-compliance can help eliminate this problem. Aims The purpose of this study is to assess the effectiveness of patient education and interviews in improving medication adherence of renal-transplant recipients. Materials and methods This study was designed as a randomized controlled trial. Using the G*Power program, the sample size was calculated as 60 subjects, with 30 in both the intervention groupand control group.Data collection tools included a patient information form,a pretest-posttest, a drug monitoring form for kidney transplant patients,the Immunosuppressive Therapy Adherence Scale, measurement of tacrolimus blood levels,and a training booklet. Results The mean knowledge score in the intervention group was 12.17±3.39 at baseline, and it increased to 20.73±1.57 after the intervention. The mean scores on the Immunosuppressant Therapy Adherence Scale were 11.67±0.55 and 10.70±0.99 in the intervention group and control group, respectively. There was a statistically significant difference between the pre-test and post-test means on the Immunosuppressant Therapy Adherence Scale in the intervention group. The mean Immunosuppressant Therapy Adherence Scalescore was higher in the intervention group. In the measurement of tacrolimus blood levels, medication adherence was found the be higher in the intervention group. The difference between the groups was statistically significant. There was a positive correlation between the tacrolimus blood levels and the Immunosuppressant Therapy Adherence Scalescores in both groups. Conclusions To conclude, our results have demonstrated that patient education and interviews improve immunosuppressant medication adherence in renal transplant recipients. Using direct or indirect methodsproved similar outcomes, suggesting that both evaluation methods are safe.

Usage of Thromboelastography With Platelet Mapping Assay to Predict Graft Thrombosis in Lower Extremity Revascularization

Hypercoagulability is one of the most commonly implicated causes of graft and stent thrombosis, and the current strategies for prevention after revascularization have relied on antiplatelet and anticoagulation medication. Existing coagulation tests might not reflect in vivo coagulation and do not measure parameters such as platelet function. The use of thromboelastography with platelet mapping (TEG-PM) aims to assay the clot strength with consideration of inherent platelet resistance to medications and might provide an integral key to the next stage of patient-centered, personalized thromboprophylaxis.

Posttransplant renal allograft dysfunction – A retrospective observational study

Background: In India, a large number of end-stage renal disease patients are undergoing renal replacement therapy. A successful renal transplantation relives the burden of dialysis with improved quality of life and a productive life thereafter. This also reduces the cost of health care to the government and the society. Graft dysfunction is an important cause of graft loss.The objective of this retrospective study is to evaluate the graft dysfunction and its impact on patient and graft survival. Methods: We did a retrospective record-based analysis of 83 cases (including both deceased and live-related renal transplants) from 2014 to 2019 who were on triple immunosuppression (tacrolimus, mycophenolate mofetil, and steroids) as maintenance therapy. Patients who had graft dysfunction, underwent graft biopsy and were analyzed subsequently. Results: The most common causes for graft dysfunction on biopsy were acute rejection, acute tubular injury, and calcineurin inhibitor toxicity. About 39% of the patients had infections, predominantly bacterial and viral infections. The rejections were associated with poor patient survival (statistically significant). The overall patient survival at our center after 1 year and 3 years was 88% and 84%, respectively, while the death-censored graft survival was 86% and 81%, respectively. Conclusion: In our center, following renal transplantation, patients had a fairly successful outcome. However, early detection and prompt management of the graft dysfunction can improve the graft and the patient survival.

Evaluation of the Graft Kidney in the Early Postoperative Period: Performance of Contrast-Enhanced Ultrasound and Additional Ultrasound Parameters.

To evaluate the various quantitative parameters of Doppler ultrasound, contrast-enhanced ultrasound (CEUS), and shear wave elastography (SWE) of graft kidneys in the early postoperative period and to explore their utility in the diagnosis of parenchymal causes of graft dysfunction. In this ethically approved study, consecutive patients who underwent renal transplantation from March 2017 to August 2018 were recruited, and those with urologic or vascular complications and those who denied consent were excluded. All patients underwent ultrasound with Doppler, SWE, CEUS (using sulfur hexafluoride), and renal scintigraphic examinations 3 to 10 days after transplantation. A composite reference standard was used, including the clinical course, renal function test results, urine output, and histopathologic results for graft dysfunction. Cortical SWE values, quantitative CEUS parameters (generated from a time-intensity curve), and their ratios were analyzed to identify graft dysfunction and differentiate acute tubular necrosis (ATN) from acute rejection (AR). Of the 105 patients included, 19 developed graft dysfunction (18.1%; 12 ATN, 5 AR, and 2 drug toxicity) in the early postoperative period. The peak systolic velocity in the interpolar artery showed a significant difference between control and graft dysfunction groups (P < .001) as well as between ATN and AR (P=.019). Resistive indices and SWE did not show significant differences. Ratios of the time to peak showed a significant difference between control and graft dysfunction groups (P < .05). The rise time and fall time of the large subcapsular region of interest and the rise time ratio were significantly different between ATN and AR (P=.03). Contrast-enhanced ultrasound can be used to diagnose parenchymal causes of early graft dysfunction with reasonable diagnostic accuracy.

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients

Rationale & ObjectiveThe Kidney Failure Risk Equation (KFRE) is a simple widely validated prediction model using age, sex, estimated glomerular filtration rate, and urinary albumin-creatinine ratio to predict the risk for end-stage kidney disease. Data are limited for its applicability to kidney transplant recipients.Study DesignValidation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.Setting & ParticipantsAdult kidney transplant recipients with functioning kidney allografts at least 6 months posttransplantation from 30 centers in the United States, Canada, and Brazil. Participants with estimated glomerular filtration rates < 60 mL/min/1.73 m2 at study entry were included.Predictor2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry.OutcomeGraft loss, defined by initiation of dialysis.Analytical ApproachDiscrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss.Results2,889 participants were included. Within 2 years, 98 participants developed graft loss, 107 participants died with a functioning graft, and 129 participants were lost to follow-up, and by 5 years, 252 had developed graft loss, 265 died with a functioning graft, and 1,543 were lost to follow-up. The KFRE demonstrated accurate calibration and discrimination (C statistic, 0.85 [95% CI, 0.81-0.88] at 2 years and 0.81 [95% CI, 0.78-0.84] at 5 years); performance was similar regardless of donor type (living vs deceased) and graft vintage, with the noted exception of poorer calibration for graft vintage less than 2 years.LimitationsUnavailable cause of graft loss.ConclusionsThe KFRE accurately predicted the risk for graft loss among adult kidney transplant recipients with graft vintage longer than 2 years and may be a useful prognostic tool for nephrologists caring for kidney transplant recipients.

Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction.

Regulatory T (Treg) cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pretransplant, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR). We found that the frequencies of total and activated Tregs at D7 were significantly lower in recipients with SAR and BPAR. Treg was more reduced in BPARs by in vitro tacrolimus treatment in the presence of basiliximab. Moreover, an early reduction of Treg frequency in rejectors was associated with a greater increase in Treg apoptosis and further attenuated IL-2 signaling. D7 Treg frequency was an independent risk factor for SAR, which was also validated for BPAR. In conclusion, first-week peripheral blood Treg frequency correlates with AR after LT under tacrolimus-based immunosuppression, which needs to be proven in larger, geographically and clinically diverse populations.

Uterus transplant graft's arterial atherosclerotic remodeling veracity.

Background:Uterus transplantation is a complex, multi-step experimental procedure used for the treatment of uterus absence or uterus anomaly that prevents embryo implantation or pregnancy completion.Method:To date, only 51 uterus transplants worldwide had been performed. When simplified, it is vascularized composite allograft transplantation. While it is still an experimental procedure with encouraging results for the future, there are still many issues that have to be clarified. The most serious complications of uterus transplantation are graft rejection or grafts vascular failure.Results:So far, no reference to the atherosclerotic arterial infiltration of the uterus arteries was suggested and studied as one of the main causes of graft's failure.Conclusion:In this review we summarized current knowledge and possible role of uterus arterial damage, including atherosclerotic changes on the graft's survival.

Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience

BackgroundSteroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss.MethodsWe identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival.Results101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft.ConclusionsAbsence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.

Involvement of metabolic, physiological and hormonal responses in the graft-compatible process of cucumber/pumpkin combinations was revealed through the integrative analysis of mRNA and miRNA expression

Grafting is a widely used technique, and graft compatibility between the rootstock and scion is a prerequisite for grafting. To date, the underlying causes of graft compatibility/incompatibility remain largely unknown. Here, using cucumber (Cucumis sativus L.) grafted onto pumpkin (Cucurbita L.) rootstocks with different degrees of graft compatibility, and both self-grafting and non-grafting as controls, an integrative analysis of mRNA and miRNA expression and regulatory networks was conducted by using RNA-Seq and sRNA-Seq at 25 days after grafting (DAG). A total of 223 differentially expressed genes (DEGs) and 30 differentially expressed miRNAs (DEMs) related to graft compatibility were identified based on their fold change. Using a combination of GO annotations and KEGG pathway data, the functional annotations and pathways of DEGs and DEM targets showed that a number of metabolic, physiological and hormonal responses are involved in graft compatibility in cucumber leaves including metabolic processes (e.g., “carbohydrate metabolic processes”), nutrient transport (e.g., “sugar transport”), signal transduction (e.g., “MAPK cascade”), plant hormone signal transduction (e.g., “abscisic acid-activated signaling pathway”), transcription factors (e.g., MYB, NAC and bHLH), oxidation-reduction processes, and defense responses. The results of our comprehensive analysis suggested that compatible rootstocks might possess a greater ability for cell proliferation and a more efficient carbohydrate metabolism that promotes plant growth. In contrast, incompatible grafts induced multiple defense response-related genes and various transcription factors, likely in response to stress. Additionally, they consumed large amounts of energy, which ultimately restrained the plants normal development. This study advances our understanding of the molecular mechanisms underlying plant graft compatible/incompatible responses and provides numerous mRNA and miRNA candidates for more in-depth studies into the graft compatibility process.

Retrospective review of a tertiary adult burn centre's experience with modified Meek grafting.

BackgroundAutologous split skin grafting is the gold standard in treating patients with massive burns. However, the limited availability of donor sites remains a problem. The aim of this study is to present our experience with the modified Meek technique of grafting, outcomes achieved and recommendations for optimized outcomes.MethodsWe retrospectively reviewed patient records from our tertiary referral burn centre and the Bi-National Burns Registry to identify all patients who had modified Meek grafting between 2010 and 2013. Patient records were reviewed individually and information regarding patient demographics, mechanism of injury and surgical management was recorded. Outcome measures including graft take rate, requirement for further surgery and complications were also recorded.ResultsEleven patients had modified Meek grafting procedures. The average age of patients was 46 years old (range 23 – 64). The average total body surface area (TBSA) burnt was 56.75 % (range 20–80 %). On average, 87 % of the grafted areas healed well and did not require regrafting. In the regrafted areas, infection was the leading cause of graft failure.ConclusionsModified Meek grafting is a useful method of skin expansion. Similar to any other grafting technique, infection needs to be sought and treated promptly. It is recommended for larger burns where donor sites are not adequate or where it is desirable to limit their extent.

Systematic Computer Tomographic Scans 7 Days After Liver Transplantation Surgery Can Lower Rates of Repeat-transplantation Due to Arterial Complications

Arterial complications are a major cause of graft lost after liver transplantation (LT). The aim of our study was to assess the clinical impact of systematic early postoperative injected computed tomographic (CT) scans after LT rather than its performance on demand in the event of abnormalities. Two series of consecutive transplantation patients in different periods (1997–1999, 231 patients versus 2008–2010, 250 patients) were analyzed. During the first period, an injected CT scan was only performed in the event of clinical, biological, or ultrasound abnormalities revealed by tests performed daily during the first week after surgery. During the second period, in addition to standard follow-up examination, an injected CT scan was performed systematically at approximately postoperative day 7. During the first (versus the more recent) period, both recipients (whose ages were 46 ± 13 years versus 50 ± 12 years; P = .004) and donors (whose ages were 42 ± 17 versus 52 ± 17 years; P = .0001) were younger and end-stage liver disease was more common (34% versus 12%; P = .0001), but hepatocellular carcinoma (7% vs 26%; P = .0001) and retransplantation (2% versus 7%; P = .01) were less frequent. Postoperative mortality was higher during the first period (14% versus 4%; P = .0003). The incidence of early arterial thrombosis (<1 month) was similar (1.3% versus 1.6%; P = .78), but that of arterial stenosis was higher with a systematic CT scan (1.7 versus 4.4; P = .07). As a consequence of the early detection and treatment of arterial abnormalities, the repeat LT rate due to late arterial thrombosis was nil in the second period and 2.1% (5/231) in the first period. In conclusion, a systematic CT angiogram at the end of the first postoperative week reduced retransplantation rates due to late hepatic artery thrombosis by detecting patients at risk who required specific treatment.

Etiology of GVHD: Alloreactivity or Impaired Cellular Adaptation?

According to the self-nonself model of immunity, allogeneic T cells are considered as major cause of graft versus host disease (GVHD) following allogeneic stem cell transplantation (SCT). On the other hand, the danger model of immunity suggests that transplant-associated recipient tissue injury rather than donor-derived alloreactive T cells is the main cause of GVHD. What has been less appreciated are the early, both conditioning-dependent and conditioning-independent, events that impair homeostatic cellular adaptations and host-protective immune responses leading to the development of tissue-specific GVHD. The notion of gut injury precipitating in GVHD has been acknowledged by clinicians, with the shift to reduced intensity-conditioning regimens that prevent acute tissue injury and are less disruptive of tissue adaptation to T cell attack. Also, the role of host-protective immune response against pathogens in preventing GVHD has been shown by the lack of severe GVHD in germ free mice as well as an impaired anti-viral immune response during chronic GVHD. This article provides a brief review of the literature on GVHD and suggests that transplant-induced dysregulation of the protective immune response in the recipient of SCT is more important than allogeneic T cells in causing GVHD.

The Back Table Graft Arterial Anastomosis Between Splenic Artery and Superior Mesenteric Artery: A 13-Year Single-Center Experience of Pancreas Transplantation in Barcelona.

Introduction:Vascular complications following pancreas transplantation are the leading non-immunologic cause of graft loss.The arterial vascular reconstruction including a Y-graft interposition from the donor iliac artery bifurcation is the most used worldwide. Aim:We sought to assess the incidence of vascular complications after using the back-table graft arterial anastomosis between splenic artery (SA) and distal superior mesenteric artery (SMA). Methods:This was a retrospective analysis including all pancreas transplants performed over 13 years (2001-2013).For the bench reconstruction, the SMA was distally dissected and sewn to the SA in an end-to-end fashion (SMA/SA).The proximal SMA with an aortic patch was anastomosed to the recipient common iliac artery. In a few cases the arteries were reconstructed with an iliac arterial “Y” graft. Vascular complications were included, focusing on arterial events. Results: A total of 273 pancreas transplantations were done:223 simultaneous pancreas kidney, 2 pancreas alone,17 pancreas after kidney and 31 retransplantations. At the bench procedure SMA/SA anastomosis was performed in 92.3% of the patients, arterial iliac “Y” graft in 17 patients,and no arterial reconstruction was need in 4 patients because of anatomical variations of the donor pancreas. Sixty-six patients presented vascular complications;venous complications were the most frequent (53 recipients).There were 16 patients with arterial complications (5.55% SMA/SA, 11.76% Y-graft).Eleven were acute arterial complications (1 enteric anastomosis bleeding with SMA thrombosis and 10 thrombosis).Five patients presented late arterial complications(Chronic arterial thrombosis (1);arterial anastomosis pseudoaneurism(1);enteroarterial fistula (3)).The patient survival with SMA/SA anastomosis at 1st and 5th year was 98.8% and 95.4%.The patient survival for arterial “Y” Graft was 100% at 1st and 93 % the 5th year.The graft survival with SMA/SA anastomosis at 1st and 5th year was 87.2% and 76.7%; and 93% using arterial “Y” Graft. Conclusions:The back table procedure used in our institution (SMA/SA) is an easy, effective and safe surgical technique, that can be used as a good alternative for surgeons to arterial “Y” graft.

Outcomes of De Novo Allograft Diabetic Nephropathy in Renal Allograft Recipients

Despite increased use of diabetogenic immunosuppressive drugs and increased incidence of new-onset diabetes after transplant in renal allograft recipients, there are few case studies on the subject of de novo allograft diabetic nephropathy and interstitial fibrosis/tubular atrophy without specific glomerular changes. We sought to study the outcomes of allograft diabetic nephropathy and interstitial fibrosis/tubular atrophy without specific glomerular changes in patients with new-onset diabetes after transplant. We reviewed the case records of all new-onset diabetes after transplant patients who underwent graft biopsy for graft dysfunction from 1992 to 2010. We analyzed the clinical characteristics and outcomes of new-onset diabetes after transplant patients with de novo allograft diabetic nephropathy and interstitial fibrosis/tubular atrophy without specific glomerular changes. Of the 1989 recipients, 421 patients developed new-onset diabetes after transplant and 26 underwent graft biopsy. Of the 26 patients, 9 had histopathologic evidence of de novo allograft diabetic nephropathy, and 17 had interstitial fibrosis/tubular atrophy without specific glomerular changes. The mean duration from transplant to developing novo allograft diabetic nephropathy was 115.2 months (range, 33-192 mo), and from developing new-onset diabetes after transplant to allograft diabetic nephropathy, was 109.66 months (range, 27-188.4 mo). Of the 9 patients with de novo allograft diabetic nephropathy, 3 died (33.3%), 2 reached end-stage renal disease (22.2%), and 4 remained stable (44.4%). Of the 17 with interstitial fibrosis/tubular atrophy, 2 died (11.7%), 5 developed end-stage renal disease (29.4%), and 10 remained stable on triple immunosuppression and insulin therapy during follow-up (58.8%). De novo allograft diabetic nephropathy is a significant cause of graft and patient loss in renal allograft recipients who develop new-onset diabetes after transplant.

Adverse Impact of Hepatitis C Virus Infection on Renal Replacement Therapy and Renal Transplant Patients in Australia and New Zealand

Understanding the impact of hepatitis C virus (HCV) infection in patients with end-stage renal disease before and after renal transplantation requires more data. We examined the outcomes of HCV antibody positive (HCVAb+) dialysis and renal transplant patients using the Australian and New Zealand Dialysis and Transplant registry. Two cohorts of dialysis (n=23,046) and transplant (n=7572) patients were identified. Survival outcomes, causes of mortality, and causes of graft failure were examined. Dialysis Cohort: 362 (1.6%) were HCVAb+ve. The cause of end-stage renal disease in the HCVAb+ve group was more likely to be glomerulonephritis or diabetes. Survival figures were similar at 5 years (48% vs. 47%) and 10 years (22% and 20%) for HCVAb+ve and HCVAb negative (HCVAb-ve) groups; however, the adjusted hazard ratio (aHR) for mortality was increased, 1.25 (95% confidence interval [CI], 1.07-1.46), for the HCVAb+ve cohort. Liver failure was more likely. Renal Transplantation Cohort: 140 (1.8%) were HCVAb+ve. Patient survival among HCVAb+ve and HCVAb-ve groups was 77% vs. 90% and 50% vs. 79% at 5 and 10 years, respectively. The aHR for patient death was 2.38 (95%CI, 1.69-3.37). Higher rates of death due to cardiovascular disease (aHR=2.74), malignancy (aHR=2.52), and hepatic failure (aHR=22.1) were observed. The aHR for graft loss was 1.71 (95%CI, 1.28-2.29) for HCVAb+ve patients; and glomerulonephritis, chronic allograft neuropathy, and death were more frequent causes of graft failure. On dialysis, HCVAb+ve patients had a slightly worse outcome. After renal transplantation, the HCVAb+ve cohort had a markedly worse patient and graft outcome. The impact of viral eradication on these outcomes is unknown.

Different Etiologies of Graft Loss and Death in Asian Kidney Transplant Recipients: A Report From Thai Transplant Registry

Background Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade. Patients and Methods The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths. Results Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%). Conclusion Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations.

Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single-center 12 year experience

PVT or PVS and HVOO are known causes of graft and patient loss after pediatric liver transplantation. Increased incidences of these complications have been reported in partial livers including DDSLT or LDLT. From 1997 to 2008, 241 consecutive pediatric patients received 271 hepatic grafts at a single center. Median follow-up is 1856 days. Surgical technique, demographics, lab values, and radiologic imaging procedures were obtained utilizing OTTR to evaluate the relationship of portal and hepatic complications with risk factors, patient and graft survival. Grafts were composed of 115/271 (42.4%) partial livers of which 90 (33.2%) were DDSLT and 25 (9.2%) LDLT. Of 271 patients, 156 (57.6%) received whole-sized grafts. There were six PVC in five patients with one patient requiring retransplantation (0.34%) and no patient deaths. Utilizing all three hepatic vein orifices on the recipient hepatic vena cava and the donor hepatic vein cut short enables a wide hepatic outflow tract unlikely to twist. None of the 241 patients developed early or late complications of the hepatic vein. None of the last 128 consecutive patients who received 144 grafts over seven and a half yr have developed either early or late complications of the hepatic or portal vein. Partial-graft actuarial survival was similar to whole-graft survival (87.2% vs. 85.3% at one yr; 76.6% vs. 80.2 at three yr; p = 0.488). Likewise, patient survival was similar between partial grafts and whole grafts (93.8% vs. 93.1% at one yr; 89.8% vs. 87.2% at three yr; p = 0.688) with median follow-up of 1822 (+/-1334) days. Patients receiving partial livers were significantly younger and smaller than patients receiving whole livers (p < 0.001). Portal and hepatic venous complications may have negative effects on patient or graft survival after pediatric liver transplantation. In our series, there was one graft and no patient loss related to portal or hepatic venous complications after pediatric liver transplantation over 12 yr.