Posterior Reversible Encephalopathy Syndrome (PRES) induced by Rituximab in two patients with vasculitis, and treated by hemodialysis

Abstract

Small and medium vessel vasculitides, either ANCA-associated or caused by anti-GBM antibodies, are multisystemic diseases with predominantly renal involvement that often require dialysis support; clinical remission can be induced with immunosuppressive therapies including apheretic treatments, high doses of steroids, and immune suppressants. In addition to the complications resulting from the primary pathological process, those associated with the immunosuppressive therapies are not negligible.

Reversible Posterior Encephalopathy Syndrome (PRES) is a clinical condition with a hyperacute onset, which can complicate the evolution of vasculitides while treated by immunosuppressive therapy. Relevant pathogenic factors are represented by alterations of the cerebral blood-brain barrier or vasogenic and/or brain edema phenomena, also related to uncontrolled hypertension.

We describe two cases of patients with systemic vasculitides, rapidly progressive renal failure (RPGN) requiring dialysis, and poor response to the initial immunosuppressive therapy who were treated subsequently with rituximab. PRES developed immediately after administration of the drug, which, however resulted effective on the course of the vasculitis in one case and not effective in the other.

In both cases, the subsequent radiological controls showed a total resolution of the encephalic alterations observed during the acute phase.

Keywords: PRES, Rituximab, ANCA-associated vasculitis, Anti-GBM Glomerulonephritis, Iatrogenic complications.

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Introduzione

Le vasculiti, gruppo eterogeneo di patologie accomunate da una flogosi di tipo autoimmune dei vasi di piccolo e medio calibro, sono malattie rare e comprendono la Granulomatosi con Poliangioite (GPA), incidenza annua, in Europa, di 2.5 casi per 100.000 di abitanti (1) e la Glomerulonefrite da Anticorpi anti Membrana Basale Glomerulare (GN anti-GBM), 1 caso per milione di abitanti l’anno nella popolazione caucasica (2).

 

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Steroid-resistant focal segmental glomerulosclerosis treated with cascade plasmafiltration and rituximab

Abstract

A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m²) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS. Clinical trials should be carried out for protocol approval.

Keywords: focal segmental glomerular sclerosis, steroid-resistant focal segmental glomerular sclerosis, cascade plasmafiltration, rituximab

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Introduzione

La glomerulosclerosi focale e segmentaria (FSGS) è una podocitopatia ad etiologia polimorfa, la cui risposta alla terapia è molto variabile (1). Ancora oggi l’uso dello steroide rappresenta l’approccio di prima linea e traccia l’outcome clinico indirizzando nelle forme cortico-dipendenti o cortico-resistenti, a protocolli terapeutici differenti (24). Possibili opzioni alternative prevedono l’uso degli inibitori della calcineurina (CNI), la ciclofosfamide, il micofenolato mofetile (MMF), il rituximab (RTX), l’ACTH ed l’abatacept (5, 6). Ulteriori approcci includono le tecniche aferetiche, ossia il plasma exchange (PE), la LDL aferesi (LDL-a), la plasmafiltrazione a cascata (PFC) e l’immunoassorbimento (IA) (7). Di seguito riportiamo un caso di FSGS primitiva cortico-resistente trattata con PFC e RTX. 

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Membranous glomerulonephritis (MGN), ongoing studies

Abstract

The membranous nephropathy (MN) is the major cause of nephrotic syndrome in in the adult, account for 20% of cases with annual incidence is 1 in 100.000.
In the past 10 years, the role of podocytes has been identified; environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes (receptor of phospholipase A2, thrombospondin type 1) that become targets of specific autoantibodies with subsequent complement activation. The discovery of this mechanisms has opened new horizons in the therapy of MN and novel drugs are available with more specific mechanism of action.
Rituximab, a monoclonal antibody directed against CD20 expressed by lymphocytes B, has been used in several trials and appears able to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial) with similar risk profile. Nowadays it remains to define the most effective therapeutic pattern.
In MN, the concept of targeting disease control, has permit novel therapies with specific blocking mechanisms (belimumab) and non-specific (ACTH) and new therapeutic options, such as ofatumumab, bortezomib and eculizumab, that have allowed to recognize pathological processes involved in the glomerular diseases.

Key Words: Membranous Glomerulonephritis, membranous nephropathy, Rituximab, ECULIZUMAB

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Background

La glomerulonefrite membranosa (GMN) è diagnosticata nel 20% dei casi di sindrome nefrosica dell’adulto, la sua incidenza annuale è di 1 caso ogni 100.000 per anno, vengono diagnosticati quindi 10.000 nuovi casi all’anno in Europa (1).

Negli ultimi 10 anni ne sono stati definiti i precisi meccanismi patogenetici che hanno aperto nuovi scenari di trattamento.

Cosa c’è quindi di nuovo e sostanziale nella nefropatia membranosa?

In sintesi la novità degli ultimi anni è che tale glomerulonefrite è una malattia del podocita che, probabilmente in risposta a stimoli ambientali non ancora chiaramente identificati e su una potenziale predisposizione genetica, espone epitopi di antigeni che diventano bersaglio di anticorpi che determinano attivazione del complemento.

Queste acquisizioni hanno avviato dal punto vista della ricerca una serie di vie per la comprensione dei meccanismi caratterizzanti lo sviluppo della malattia. Sono diventati quindi oggetto di studio i marcatori podocitari in grado di attivare il sistema immunitario, le cellule che producono anticorpi diretti contro gli antigeni esposti e la via di attivazione del complemento (23).
 

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