Remission of aHUS neurological damage with eculizumab

Abstract

Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by haemolytic microangiopathic anaemia, thrombocytopaenia and acute onset of renal failure, in the absence of Escherichia coli infection. Renal damage usually progresses to end-stage renal disease (ESRD), sometimes being accompanied by signs of extrarenal thrombotic microangiopathy (TMA). We report a case of full neurological and haematological recovery after eculizumab treatment in a patient with ESRD secondary to chronic aHUS refractory to plasmatherapy while she was under dialysis. It highlights the use of eculizumab for controlling extrarenal manifestations of aHUS in this population.

Timing of eculizumab therapy for C3 glomerulonephritis

“…Thus, the question nephrologists may be asked is when is it too late to initiate therapy for a patient already on dialysis and in the absence of extrarenal symptoms, or how long should therapy be maintained in dialysis-dependent patients? Case reports and series are providing some insights that support a wide variability, with recovery of renal function observed when eculizumab was initiated after up to 4 months on dialysis and recovery of renal function up to 5 months after initiating eculizumab for a patient on dialysis, as illustrated by Inman et al (Table 1 and Figure 1 ) [ 1 , 7 – 18 ].…”

“…Unsurprisingly, prescription of eculizumab is frequently delayed in the course of complement-mediated diseases, sometimes for decades, even when kidney biopsies are available. In a recent case report, diagnosis of aHUS was made 25 years after the first episode of anaemia, thrombocytopenia and acute kidney injury [ 7 ]. In this particular case, a first renal biopsy for proteinuric kidney disease at age 15 years showed focal proliferative glomerulonephritis.…”

“…After the second eculizumab dose, renal function recovered and dialysis was discontinued, for a total of 2.5–3.5 months on dialysis [ 9 , 10 ]. These and other case reports as well as clinical trials have now established that eculizumab may be life-saving in dialysis-dependent patients with aHUS, in whom it may restore renal function even after prolonged periods of dialysis (Table 1 ) [ 1 , 7 – 18 , 19 ], it may improve life-threatening extrarenal manifestations of aHUS [ 7 ] and is required to prevent recurrence in the kidney graft for most forms of aHUS [ 20 ]. As might be expected, in a series of 12 off-trial patients, the extent of renal function recovery within 6 months correlated inversely with the time interval between the onset of the episode of aHUS and the initiation of eculizumab: all patients starting eculizumab within 28 days of the current aHUS episode recovered some renal function, while only four out of seven patients starting eculizumab after 28 days displayed improved renal function and two could not be weaned from dialysis [ 21 ].…”

Compromiso cerebrovascular agudo en síndrome hemolítico urémico: descripción de dos casos pediátricos

“…En los últimos años ha aumentado el interés en el potencial beneficio del uso de antagonistas de proteí-nas del complemento, como el eculizumab (anticuerpo monoclonal que bloquearía de manera específica e irreversible al componente C5) que permitiría frenar la cascada que lleva al desarrollo de microangiopatía trombótica y que ha demostrado eficacia y seguridad en el manejo del SHU atípico con alteraciones sistémi-cas severas 21 . Los resultados de este tratamiento en niños con compromiso neurológico severo por SHU+D aún son inciertos, por lo que es necesario evaluar crí-ticamente los resultados de los estudios que se llevan a cabo en la actualidad antes de recomendar su uso [7][8][9][10]22 .…”

“…Igualmente, aunque no hay lesiones simétri-cas en la protuberancia que semejen una mielinolisis central pontina, las lesiones bilaterales periventriculares pudieran sugerir una mielinolisis central extrapontina, por corrección rápida de la natremia. En ambos casos no tenemos este antecedente que es necesario tener presente al momento de tratar un niño con SHU 21 .…”