Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab

Delbue, Serena; Ferraresso, Mariano; Elia, Francesca; Belingheri, Mirco; Carloni, Camilla; Signorini, Lucia; Carluccio, Silvia; Dallari, Simone; Ghio, Luciana; Ferrante, Pasquale

doi:10.1002/jmv.23339

Cited by 19 publications

(22 citation statements)

References 54 publications

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“…However, in our study neither the use of ATG or rituximab given within the first year after transplantation was associated with BK viremia. In line with this observation polyoma virus replication was not associated with rituximab therapy in pediatric patients with nephrotic syndrome [24]. …”

Section: Discussionmentioning

confidence: 67%

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

et al. 2013

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BackgroundPolyomavirus BK nephropathy (PyVAN) remains an important cause of early graft dysfunction and graft loss in kidney transplantation.MethodsIn this retrospective, single centre cohort study we studied the incidence and outcome of BK viral infection in 352 patients transplanted in 2008–2011.ResultsDuring follow-up viral replication was detected in 48 patients (13.6%); 22 patients (6.2%) had biopsy proven PyVAN.In multivariate logistic regression analyses risk factors for BK-viremia were lack of enrolment into randomized controlled trials (RCTs), biopsy proven acute rejections, cytomegaly virus (CMV) serostatus of both donor and recipient and previous transplantation.In patients without PyVAN reduction or switch of immunosuppression was associated with rapid viral clearance and stable graft function. In contrast, in most patients with PyVAN graft function deteriorated and 5 patients prematurely lost their allograft. Switch of immunosuppression to a low dose cyclosporine plus mTOR inhibitor based regimen in patients with PyVAN was safe, well tolerated and tended to be associated with a better short-term outcome in terms of graft function compared to reduction of existing immunosuppression alone.ConclusionsWith the lack of licensed anti-polyoma viral drugs reduction or conversion of immunosuppression remains the mainstay of therapy in patients with PyVAN. The combination of low dose cyclosporine plus mTOR inhibition appears to be safe and warrants further investigation.

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Section: Discussionmentioning

confidence: 67%

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

et al. 2013

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“…Actually, finding that JCV and BK virus (BKV) replication in blood, serum, and urine samples was not affected by rituximab therapy in children with recurrent idiopathic NS [39] provides additional evidence that the facilitating effect of rituximab on complications related to viral reactivations (if any) should not exceed that of other unspecific immunosuppressants. …”

Section: Rituximabmentioning

confidence: 99%

Rituximab in Primary Membranous Nephropathy: First-Line Therapy, Why Not?

2014

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The ideal treatment of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) is still a matter of debate. This is a major issue since these patients may progress to end-stage kidney disease (ESKD) in 5-10 years. Steroids, alkylating agents, and calcineurin inhibitors have been suggested to achieve NS remission and prevent ESKD in this population. Treatment benefits, however, are uncertain and are often offset by serious adverse events (SAEs). Evidence that B cells play a crucial role in the pathogenesis of the disease, both as precursors of autoantibody-producing cells and as antigen-presenting cells, provided the background for explorative studies testing the role of B cell-depletion therapy with the monoclonal antibody rituximab. This approach aimed at selectively inhibiting disease mechanisms without the devastating consequences of unspecific immunosuppression. Finding that rituximab safely ameliorated NS in 8 patients with primary MN fueled a series of observational studies that uniformly confirmed the safety/efficacy profile of rituximab in this context. Although head-to-head comparisons in randomized clinical trials are missing, comparative analyses between series of homogeneous patient cohorts clearly show at least similar efficacy of rituximab as compared to steroid plus alkylating agents. Moreover, data confirm the dramatically superior safety profile of rituximab that actually appears to be associated with a rate of SAEs even lower than that observed with conservative therapy. Rituximab is also effective in patients resistant to other treatments and its cost-effectiveness is further increased when treatment is titrated to circulating B cells. Recently identified pathogenic antibodies against the M type phospholipase A₂ receptor will likely provide a novel tool to monitor disease activity and drive rituximab therapy, at least in a subset of patients. Newly developed anti-CD20 antibodies could represent a valuable option for those who fail rituximab therapy. Steroids, alkylating agents, and calcineurin inhibitors should likely be abandoned.

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“…The therapeutic effects can be attributed to the elimination of preconditioned B cells from circulation and reconstitution of the naïve B-cell subpopulation since pediatric ABMR patients who did not relapse after rituximab demonstrated a higher percentage of naïve B cells after repopulation [68], suggesting that the B-cell repertoire has been reprogrammed and has less propensity to form a pre-programmed immune response towards the alloantigen and thus re-achieve desensitization. Some use of rituximab is associated with increased incidences BK nephropathy [74] and other infections [72]; however, larger studies [71,75] have suggested that there is no significant difference in infectious complications when compared with other treatments. However, in cancer studies, an increased incidence of interstitial pneumonitis has been observed when rituximab is added to the regimen [76].…”

Section: Cell Depletionmentioning

confidence: 99%

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Singh

Sarwal

2015

Drugs

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Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

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Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab

Cited by 19 publications

References 54 publications

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

Rituximab in Primary Membranous Nephropathy: First-Line Therapy, Why Not?

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

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