Introduction Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown.Methods 15 patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months.Results Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the followup, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3 and CASK) involved in podocyte, mesangial and tubular restoration.Conclusion TCZ adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.

Severe acute respiratory syndrome coronavirus 2 (named SARS CoV-2/COVID-19) is a novel pandemic infectious disease, which emerged in Wuhan, China, in late December 2019 and spread rapidly worldwide. 1,2 At the time we are writing (05/10/2020), in Italy there are about 219 000 patients infected, 28 600 only in Piedmont, our region. 3 Clinically, the disease is characterized with fever, cough, dyspnea, diarrhea, and eventually respiratory failure. 4,5 According to their intrinsic frailty and comorbidities, transplanted patients were considered a high-risk population. 6,7 Tocilizumab (TCZ), a humanized monoclonal antibody against interleukin-6 (IL-6) receptor widely adopted in adult rheumatoid arthritis and also used as rescue therapy for chronic antibody-mediated rejection in kidney transplantation, 8 has been recently registered for the treatment of severe or life-threatening chimeric antigen receptor T-cell induced cytokine release syndrome (CRS) in adult and pediatric patients. 9 In this context, because the development of acute respiratory distress syndrome (ARDS) in COVID-19 pneumonia has been associated with activation of the immune system and consequent cytokine storm with high levels of IL-6, some initial reports suggested a beneficial role of this drug, 10,11 also in solid organ transplanted patients. 12 Herein, we reported our experience in 6 kidney transplanted patients treated with TCZ after occurrence of COVID-19 infection.

Focal segmental glomerulosclerosis (FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts (30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.

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