Bortezomib-containing multimodality treatment for antibody-mediated rejection with anti-HLA and anti-AT1R antibodies after kidney transplantation

For decades, the human leukocyte antigen (HLA) complex has been considered the primary target of antibody-mediated rejection (AMR), and treatment strategies have mainly focused on anti-HLA antibodies. Recently, other antibodies potentially causing organ damage and loss have been discovered. Conclusive evidence on treatment options for these subtypes of AMR is still lacking. After an experience previously reported in this journal,1 we describe a case of late-onset AMR, with mixed anti-HLA and anti-angiotensin II type 1 receptor (AT1R) antibodies, that was successfully treated with a multimodal approach, including the use of the proteasome inhibitor bortezomib

Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS

The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition

Infezioni urinarie nel trapiantato renale

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Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

Background The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. Methods We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard), and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1–16). Implantation biopsy score (IBS), a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF), creatinine clearance (1st, 3rd and 5th posttransplant year) and graft and patient survival at 1 and 5 years were evaluated. Results Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Conclusions Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant) but not patient survival was predicted by IBS

La patologia da Citomegalovirus nel paziente portatore di trapianto renale: impatto, prevenzione e trattamento:

Cytomegalovirus infection during renal transplantationRenal transplantation (RT) is considered the best therapy for patients with chronic renal failure. Renal transplant patients have an elevated r..

A Keynesian perspective on the health economics of kidney transplantation would strengthen the value of the whole organ donation and transplantation service

BackgroundIn this study, the Keynesian principle “savings may be used as investments in resources” is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity.MethodsWe analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs.ResultsThe ODT activity reached a peak in 2017, declining through 2018–2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million.ConclusionThe financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT

Clinical and Surgical Challenges in Kidney Transplantation: Toward a Personalized Approach?

The continuously evolving practice of solid organ transplantation (SOT) in general and kidney transplantation (KT) in particular embodies the complexity of a composite, multi-step healthcare service [...

New-Onset Diabetes after Kidney Transplantation

New-onset diabetes mellitus after transplantation (NODAT) is a frequent complication in kidney allograft recipients. It may be caused by modifiable and non-modifiable factors. The non-modifiable factors are the same that may lead to the development of type 2 diabetes in the general population, whilst the modifiable factors include peri-operative stress, hepatitis C or cytomegalovirus infection, vitamin D deficiency, hypomagnesemia, and immunosuppressive medications such as glucocorticoids, calcineurin inhibitors (tacrolimus more than cyclosporine), and mTOR inhibitors. The most worrying complication of NODAT are major adverse cardiovascular events which represent a leading cause of morbidity and mortality in transplanted patients. However, NODAT may also result in progressive diabetic kidney disease and is frequently associated with microvascular complications, eventually determining blindness or amputation. Preventive measures for NODAT include a careful assessment of glucose tolerance before transplantation, loss of over-weight, lifestyle modification, reduced caloric intake, and physical exercise. Concomitant measures include aggressive control of systemic blood pressure and lipids levels to reduce the risk of cardiovascular events. Hypomagnesemia and low levels of vitamin D should be corrected. Immunosuppressive strategies limiting the use of diabetogenic drugs are encouraged. Many hypoglycemic drugs are available and may be used in combination with metformin in difficult cases. In patients requiring insulin treatment, the dose and type of insulin should be decided on an individual basis as insulin requirements depend on the patient’s diet, amount of exercise, and renal function

Adipose-Derived Stem/Stromal Cells in Kidney Transplantation: Status Quo and Future Perspectives

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia-reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted