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Therapeutic apheresis in kidney transplantation: An updated review

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World Journal of Transplantation 2019年第6期9卷 103-122页

Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased-or living-donor transplantation. Postoperatively,additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.

关键词： Kidney transplantation Therapeutic plasma exchange Double-filtrationplasmapheresis Immunoadsorption Extracorporeal photopheresis Desensitization Antibody-mediated rejection Focal segmental glomerulosclerosis

Microbiota,renal disease and renal transplantation

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World Journal of Transplantation 2021年第3期11卷 16-36页

Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal *** microbiota has a relevant role in conditioning the healthy status and the *** particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune *** indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts *** abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic ***,after renal transplantation the microbiota changes with the appearance of pathobionts,principally in the first period because of the assumption of immunosuppressive drugs and *** changes may deeply interfere with the graft outcome causing acute rejection,renal infections,diarrhea,and renal interstitial *** addition,change in the microbiota may modify the metabolism of immunosuppressive drugs causing in some patients the need of modifying the immunosuppressant *** restoration of the indigenous microbiota after transplantation is important,either to avoiding the complications that impair the normal renal graft,and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the *** use of prebiotics,probiotics,smart bacteria and diet modification may restore the indigenous microbiota,but these studies are just at their beginning and more data are needed to draw definitive conclusions.

关键词： Gut commensals Microbioma Microbiota Renal disease Renal transplantation Transplant outcomes

Innovative immunosuppression in kidney transplantation:A challenge for unmet needs

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World Journal of Transplantation 2022年第3期12卷 27-41页

作者： Maurizio Salvadori aris tsalouchos Department of Renal Transplantation Careggi University HospitalFlorence 50139Italy Division of Nephrology Santa Maria Annunziata HospitalFlorence 50012Italy

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries,new innovative drugs in kidney transplantation are difficult to be *** best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the *** unmet needs are the prevention of delayed graft function(DGF),the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated *** needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible *** first are particularly exposed to DGF,the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often *** caution is needed in treating these ***,they are described in very recent studies and the follow-up of their effect is of course rather ***,some of these drugs are still in an early phase of study,even if in well-conducted randomized controlled *** caution and a careful check need to be used in trials launched 2 or 3 years ***,is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.

关键词： New drugs Unmet needs in kidney transplantation Delayed graft function Long-term outcomes Kidney inflammation Anti-human leukocyte antigen antibodies

Hepatitis C and renal transplantation in era of new antiviral agents

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World Journal of Transplantation 2018年第4期8卷 84-96页

作者： Maurizio Salvadori aris tsalouchos Department of Transplantation Renal Unit Careggi University Hospital Nephrology and Dialysis Unit Saints Cosmas and Damian Hospital

Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.

关键词： Hepatitis C virus Renal transplantation Hepatitis C virus and renal diseases Interferon based therapies Direct antiviral agents Hepatitis C viruspositive donors

Immunoglobulin G4-related kidney diseases: An updated review

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World Journal of Nephrology 2018年第1期7卷 29-40页

作者： Maurizio Salvadori aris tsalouchos Renal Unit Department of Transplantation Careggi University Hospital Division of Nephrology Nephrology and Dialysis Unit Saints Cosmas and Damian Hospital

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases( IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4+ cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the secondline treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment.

关键词： Immunoglobulin G4-related disease Storiform fibrosis Lymphoplasmacytic infiltration Tubulointerstitial nephritis Steroid treatment B cell depleting agents

Pharmacogenetics of immunosuppressant drugs:A new aspect for individualized therapy

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World Journal of Transplantation 2020年第5期10卷 90-103页

作者： Maurizio Salvadori aris tsalouchos Department of Renal Transplantation Careggi University HospitalFlorence 50139Italy Nephrology and Dialysis Unit Saints Cosmas and Damian HospitalPescia 51017Italy

In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate ***,pharmacogenetics may exert its action on immunosuppressant drugs at three *** identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug *** is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several *** concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic *** course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been *** genes on the basis of relevant studies have been proposed as good candidates for future ***,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is *** conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.

关键词： Immunosuppressant pharmacokinetics Immunosuppressant pharmacodynamics Immunosuppressant pharmacogenetics Immunosuppressant pharmacogenomics Transplantation Immunosuppressant drugs

Antineutrophil cytoplasmic antibody associated vasculitides with renal involvement: Open challenges in the remission induction therapy

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World Journal of Nephrology 2018年第3期7卷 71-83页

作者： Maurizio Salvadori aris tsalouchos Department of Nephrology and Renal Transplantation Careggi University Hospital Department of Nephrology and Dialysis Saints Cosmas and Damian Hospital

Renal involvement with rapidly progressive glomeru-lonephritis is a common manifestation of antineutrophil cytoplasmic antibody(ANCA) associated vasculitides, which is characterized by end-stage renal disease and high mortality rates in untreated and/or late referral patients. The long-term renal survival has improved dramatically since the addition of cyclophosphamide(CYC) and recently of rituximab(RTX) in association with corticosteroids in the remission induction thera-peutic regimens. However, renal prognosis remains unfavorable for many patients and the mortality rate is still significantly high. In this review, we analyze the open challenges to be addressed to optimize the induction remission therapy, principally in patients with advanced kidney failure. This concern the first-line therapy(CYC or RTX) based on different parameters(estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, safety), the role of plasma exchange and the role of new therapies. Indeed, we discuss future perspectives in induction remission therapy by reporting recent advances in new targeted therapies with particular reference to avacopan, an orally administered selective C5a receptor inhibitor.

关键词： Rapidly progressive glomerulonephritis Remission induction therapy Antineutrophil cytoplasmic antibody associated vasculitides Cyclophosphamide Rituximab Corticosteroids Plasma exchange Avacopan

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

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World Journal of Transplantation 2019年第4期9卷 62-80页

作者： Maurizio Salvadori aris tsalouchos Department of Transplantation Renal Unit Careggi University Hospitalviale Pieraccini 18Florence 50139Italy Nephrology and Dialysis Unit Saints Cosmas and Damian HospitalVia Cesare BattistiPescia (PT) 2-51017Italy

Organ shortage represents one of the major limitations to the development of kidney *** increase the donor pool and to answer the ever increasing kidney request,physicians are recurring to marginal kidneys as kidneys from older donors,from hypertensive or diabetic donors and from nonheart beating *** kidneys are known to have frequently a worse outcome in the *** date major problem is to evaluate such kidneys in order to use or to discard them before *** use of such kidneys create other relevant question as whether to use them as single or dual transplant and to allocate them fairly according transplant *** pre-transplant histological evaluation,the clinical evaluation of the donor or both the criteria joined has been used and according the time each criterion prevailed over the *** of this review has been to examine the advantages and the drawbacks of any criterion and how they have changed with *** date any criterion has several limitations and several authors have argued for the development of new guidelines in the field of the kidney evaluation for *** authors argue that the use of omic technologies should improve the organ evaluation and studies are ongoing to evaluate these technologies either in the donor urine or in the biopsies taken before transplantation.

关键词： Kidney evaluation Pre-transplant biopsies Kidney donor evaluation Kidney risk profile index Omic technologies Deceased donor score Donor risk score

Biomarkers in renal transplantation:An updated review

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World Journal of Transplantation 2017年第3期7卷 161-178页

作者： Maurizio Salvadori aris tsalouchos Renal Unit Department of TransplantationCareggi University Hospital Division of Nephrology Careggi University Hospital

Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.

关键词： Renal transplantation Biomarkers Genomic Proteomics Transplant outcome Molecular signatures