Avances en la inmunosupresión para el trasplante renal. Nuevas estrategias para preservar la función renal y reducir el riesgo cardiovascular

The development of new immunosuppressants for renal transplantation is aimed not only at improving short-term outcomes, but also at achieving better safety, cardiovascular, and metabolic profiles and at decreasing nephrotoxicity. Belatacept is a fusion protein that inhibits T cell activation by binding to CD80 and CD86 antigens. Clinical trials, particularly the BENEFIT and BENEFIT-EXT studies, have shown that belatacept preserves function and structure in renal grafts. The effects of belatacept provide long-term, sustained results, and the safety and efficacy of this drug have been demonstrated in cases of renal transplantation from expanded criteria donors. Compared to calcineurin inhibitors, belatacept is associated with a lower incidence of chronic allograft nephropathy and a more favourable cardiovascular and metabolic profile

Tissue engineering by decellularization and 3D bioprinting

Discarded human donor organs have been shown to provide decellularized extracellular matrix (dECM) scaffolds suitable for organ engineering. The quest for appropriate cell sources to satisfy the need of multiple cells types in order to fully repopulate human organ-derived dECM scaffolds has opened new venues for the use of human pluripotent stem cells (hPSCs) for recellularization. In addition, three-dimensional (3D) bioprinting techniques are advancing towards the fabrication of biomimetic cell-laden biomaterial constructs. Here, we review recent progress in decellularization/recellularization and 3D bioprinting technologies, aiming to fabricate autologous tissue grafts and organs with an impact in regenerative medicine

Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso

Trobareu una actualització (2015) d'aquest document a: http://hdl.handle.net/2445/99427Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Atypical HUS (aHUS) is a sub-type of HUS in which the TMA phenomena are the consequence of decreased regulation of the alternative complement pathway on cell surfaces due to a genetic cause. aHUS is an extremely rare disease that, despite the administration of standard treatment with plasma therapy, often progresses to terminal chronic renal failure with a high associated rate of mortality. In recent years, research has established the key role that the complement system plays in the induction of endothelial damage in patients with aHUS, through the characterisation of multiple mutations and polymorphisms in the genes that code for certain complement factors. Eculizumab is a monoclonal antibody that inhibits the terminal fraction of the complement protein, blocking the formation of a cell membrane attack complex. In prospective studies in patients with aHUS, administering eculizumab produces a rapid and sustained interruption in the TMA process, with significant improvements in long-term renal function and an important decrease in the need for dialysis or plasma therapy. In this document, we review and bring up to date the important aspects of this disease, with special emphasis on how recent advancements in diagnostic and therapeutic processes can modify the treatment of patients with aHUS

Uso terapéutico de las vesículas extracelulares en insuficiencia renal aguda y crónica

En la década de los 90 se descubrió un nuevo sistema de comunicación célula-célula, que consiste en la liberación de vesículas cargadas con partículas bioactivas (proteínas, mRNA, miRNA, metabolitos, etc.) en el espacio extracelular. Este tipo de comunicación se ha conservado durante la evolución, hecho que justificaría que la mayoría de los tipos celulares puedan generarlas. Estas vesículas extracelulares (VE) pueden regular diversos procesos fisiológicos, así como el desarrollo y progresión de enfermedades. En los últimos anos se ha extendido el estudio de las VE generadas principalmente por células madre adultas o embrionarias, células sanguíneas, células del sistema inmune y nervioso, así como células tumorales. El análisis de VE en fluidos corporales ha sido utilizado como herramienta de diagnóstico en cáncer y recientemente para distintas enfermedades renales. Sin embargo, en esta revisión pretendemos analizar la importancia, función y posible aplicación clínica de las VE generadas por células madre en enfermedades renales y en trasplantes

Outcomes of patients with atypical haemolytic uraemic syndrome with native and transplanted kidneys treated with eculizumab: a pooled post hoc analysis

Atypical hemolytic uremic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant, and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, hematologic and renal parameters, and adverse events. Of 100 patients, 74 had native kidneys and 26 in the transplant subgroup had a collective history of 38 grafts. No patients lost grafts and only one with preexisting ESRD received a transplant on treatment. Efficacy endpoints were achieved similarly in both subgroups. After 26 weeks, mean absolute estimated glomerular filtration rate increased from baseline to 61 and 37 mL/min/1.73 m2 in native (n=71; P<0.0001) and transplanted kidney (n=25; P=0.0092) subgroups. Two patients (one/subgroup) developed meningococcal infections; both recovered, one continued therapy. Eculizumab was well tolerated. Eculizumab improved hematologic and renal outcomes in both subgroups. In patients with histories of multiple graft losses, eculizumab protected kidney function. (ClinicalTrials. gov numbers : NCT00844545, NCT00844844, NCT00838513, NCT00844428, NCT01193348, and NCT01194973) This article is protected by copyright. All rights reserved

First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy

Purpose of reviewEarly and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe.Recent findingsThe low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes.SummaryThis review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.</p

Thrombotic microangiopathies assessment: mind the complement.

When faced withmicroangiopathic haemolytic anaemia, thrombocytopenia and organ dysfunction, clinicians should suspect thrombotic microangiopathy (TMA). The endothelial damage that leads to this histological lesion can be triggered by several conditions or diseases, hindering an early diagnosis and aetiological treatment. However, due to systemic involvement in TMA and its lowincidence, an accurate early diagnosis is often troublesome. In the last few decades,major improvements have been made in the pathophysiological knowledge of TMAs such as thrombotic thrombocytopenic purpura [TTP, caused by ADAMTS-13 (a disintegrin andmetalloproteinase with a thrombospondin Type 1motif,member 13) deficiency] and atypical haemolytic uraemic syndrome (aHUS, associated with dysregulation of the alternative complement pathway), together with enhancements in patientmanagement due to newdiagnostic tools and treatments. However, diagnosis of aHUS requires the exclusion of all the other entities that can cause TMA, delaying the introduction of terminal complement blockers, which have shown high efficacy in haemolysis control and especially in avoiding organ damage if used early. Importantly, there is increasing evidence that other forms of TMA could present overactivation of the complement system, worsening their clinical progression. This review addresses the diagnostic and therapeutic approach when there is clinical suspicion of TMA, emphasizing complement evaluation as a potential tool for the inclusive diagnosis of aHUS, as well as for the improvement of current knowledge of its pathophysiological involvement in other TMAs. The development of both new complement activation biomarkers and inhibitory treatments will probably improve themanagement of TMA patients in the near future, reducing response times and improving patient outcomes

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection

BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications