Management and prevention of post-transplant malignancies in kidney transplant recipients

The central issue in organ transplantation remains suppression of allograft rejection. Thus, the development of immunosuppressive drugs has been the key to successful allograft function. The increased immunosuppressive efficiency obtained in the last two decades in kidney transplantation dramatically reduced the incidence of acute rejection. However, the inevitable trade-off was an increased rate of post-transplant infections and malignancies. Since the incidence of cancer in immunosuppressed transplant recipients becomes greater over time, and the introduction of new immunosuppressive strategies are expected to extend significantly allograft survival, the problem might grow exponentially in the near future. Thus, cancer is becoming a major cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. There are at least four distinct areas requiring consideration, which have a potentially serious impact on recipient outcome after transplantation: (i) the risk of transmitting a malignancy to the recipient within the donor organ; (ii) the problems of previously diagnosed and treated malignancy in the recipient; (iii) the prevention of de novo post-transplant malignant diseases and (iv) the management of these complex and often life-threatening clinical problems. In this scenario, the direct and indirect oncogenic potential of immunosuppressive therapy should be always carefully considered

Editorial: Kidney Transplantation and Innate Immunity

No abstract availabl

The role of tubular cells in the progression of renal damage: guilty or innocent?

The progressive development of sclerosis in remnant glomeruli after the initial renal damage is caused by hyperfiltration. Thus, there is a progressive decrease in the number of glomeruli connected..

The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

Natural killer cells (NK) represent a population of lymphocytes involved in innate immune response. In addition to their role in anti-viral and anti-tumor defense, they also regulate several aspects of the allo-immune response in kidney transplant recipients. Growing evidence suggests a key role of NK cells in the pathogenesis of immune-mediated graft damage in kidney transplantation. Specific NK cell subsets are associated with operational tolerance in kidney transplant patients. On the other side, allo-reactive NK cells are associated with chronic antibody-mediated rejection and graft loss. Moreover, NK cells can prime the adaptive immune system and promote the migration of other immune cells, such as dendritic cells, into the graft leading to an increased allo-immune response and, eventually, to chronic graft rejection. Finally, activated NK cells can infiltrate the transplanted kidney and cause a direct graft damage. Interestingly, immunosuppression can influence NK cell numbers and function, thus causing an increased risk of post-transplant neoplasia or infection. In this review, we will describe how these cells can influence the innate and the adaptive immune response in kidney transplantation and how immunosuppression can modulate NK behavior

Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis.

Protease-activated receptor (PAR)-1 is a cellular receptor for thrombin that is activated after proteolytic cleavage. The contribution of PAR-1 to inflammatory cell-mediated renal injury was assessed in murine crescentic glomerulonephritis (GN). A pivotal role for thrombin in this model was demonstrated by the capacity of hirudin, a selective thrombin antagonist, to attenuate renal injury. Compared with control treatment, hirudin significantly reduced glomerular crescent formation, T cell and macrophage infiltration, fibrin deposition, and elevated serum creatinine, which are prominent features of GN. PAR-1-deficient (PAR-1(-/-)) mice, which have normal coagulation, also showed significant protection from crescentic GN compared with wild-type mice. The reductions in crescent formation, inflammatory cell infiltration, and serum creatinine were similar in PAR-1(-/-) and hirudin-treated mice, but hirudin afforded significantly greater protection from fibrin deposition. Treatment of wild-type mice with a selective PAR-1-activating peptide (TRAP) augmented histological and functional indices of GN, but TRAP treatment did not alter the severity of GN in PAR(-/-) mice. These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1-dependent effects that augment inflammatory renal injury

Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review on incidence, risk factors, pathophysiology and management of immunosuppressive therapy

Abstract Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications