The impact of preservation fluid culture on graft site arteritis: a systematic review and metanalysis

The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear

Current Perspectives in ABO-Incompatible Kidney Transplant

For a long time, ABO incompatible living donor kidney transplantation has been considered contraindicated, due to the presence of isohemagglutinins, natural antibodies reacting with non-self ABO antigens. However, as the demand for kidney transplantation is constantly growing, methods to expand the donor pool have become increasingly important. Thus, in the last decades, specific desensitization strategies for ABOi transplantation have been developed. Nowadays, these regimens consist of transient removal of preformed anti-A or anti-B antibodies by using plasmapheresis or immunoadsorption and B-cell immunity modulation by CD20+ cells depletion with rituximab, in association with maintenance immunosuppression including corticosteroids, tacrolimus and mycophenolate mofetil. The outcome in ABOi kidney transplantation have markedly improved over the years. In fact, although randomized trials are still lacking, recent meta analysis has revealed that there is no difference in terms of graft and patient???s survival between ABOi and ABO compatible kidney transplant, even in the long term. However, many concerns still exist, because ABOi kidney transplantation is associated with an increased risk of bleeding and infectious complications, partly related to the effects of extracorporeal treatments and the strong immunosuppression. Thus, a continuous improvement in desensitization strategies, with the aim of minimize the immunosuppressive burden, on the basis of immune pathogenesis, antibodies titers and/or ABO blood group, is warranted. In this review, we discuss the main immune mechanisms involved in ABOi kidney transplantation, the pathogenesis of tolerance and the desensitization regimens, including immunoadsorption and plasmapheresis and the immunosuppressive protocol. Finally, we provide an overview on outcome and future perspectives in ABOi kidney transplant

Impact of the Type of Dialysis on Time to Transplantation: Is It Just a Matter of Immunity?

Background: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies

Updated diagnosis and graft involvement for visceral leishmaniasis in kidney transplant recipients: a case report and literature review

Visceral leishmaniasis (VL) has become a rising concern to transplantation teams, being associated with graft dysfunction and reduced survival of renal transplant recipients. Here, we describe a case of VL occurring in a kidney transplant (KT) recipient in Italy, a country in which Leishmania infantum is endemic and we reviewed the literature on the clinical course and diagnosis of VL in KT recipients residing or travelling to southern Europe

Histological findings of diabetic kidneys transplanted in non-diabetic recipients: a case series

Background Diabetic donors are recognized as a reliable source of organs, although the discard rate of kidneys is still high. Few data are available on the histological evolution of these organs especially on kidneys transplanted into non-diabetic patients who remain euglycemic. Methods We describe the histological evolution of ten kidney biopsies performed on non-diabetic recipients of diabetic donors. Results Mean donor age was 69 +/- 7 years, 60% were males. Two donors were treated with insulin, eight with oral antidiabetic drugs. Mean recipient age was 59.9 +/- 7 years, 70% were males. The pre-existing diabetic lesions identified in the pre-implantation biopsies, encompassed all histological classes, and were associated with mild IF/TA and vascular damages. The median follow-up was 59.5 [IQR 32.5-99.0] months; at follow-up, 40% of cases did not change histologic classification, two patients with class IIb downgraded to IIa or I and one with class III downgraded to IIb. Conversely, three cases showed a worsening, from class 0 to I, I to IIb or from IIa to IIb. We also observed a moderate evolution of IF/TA and vascular damages. At follow-up visit, estimated GFR was stable (50.7 mL/min vs. 54.8 at baseline) and proteinuria was mild (51.1 +/- 78.6 mg/day). Conclusions Kidneys from diabetic donors show variable evolution of the histologic features of diabetic nephropathy after transplant. This variability may be associated to recipients characteristics such as euglycemic milieu, in case of improvement, or obesity and hypertension, in case of worsening of histologic lesions

Early Light Chains Removal and Albumin Levels with a Double Filter-Based Extracorporeal Treatment for Acute Myeloma Kidney

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients' outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient's outcome

Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant

Background A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant. Methods We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10-14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Results Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome. Conclusions An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant

Identification of asymptomatic Leishmania infection in patients undergoing kidney transplant using multiple tests

Objectives: In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT). Methods: We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen. Results: One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood. Conclusion: Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies.This work was supported by the Italian Ministry of Health (grant number RF-2016-02361931)S

Kidney transplantation in systemic sclerosis: Advances in graft, disease, and patient outcome

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management