Eculizumab in secondary atypical haemolytic uraemic syndrome.

Background: Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods: We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results: Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion: Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.

Ischaemic stroke in incident dialysis patients.

BACKGROUND: Despite the high frequency of cardiovascular disease among the population on dialysis, there are few studies on ischaemic stroke and associated factors. The objective of the present study is to assess the prevalence of ischaemic stroke at the start of dialysis, its incidence in the course of follow-up and possible factors associated in its presentation. METHODS: All patients in our dialysis programme between 1 January 1999 and 31 December 2005 were included in the study and followed up until death, transplant, transfer out of our catchment area, or conclusion of the study on 31 December 2008. Factors analysed were age, gender, smoking habit, diabetes, hypertension, previous ischaemic stroke, ischaemic coronary disease, peripheral vascular disease and atrial fibrillation. Other factors measured in the first month of dialysis were haematocrit, urea, creatinine, lipids, calcium, phosphorus, parathyroid hormone and albumin. RESULTS: Of 449 patients included in the study (age 64.4 ± 16 years), 30 commenced dialysis having had previous stroke (prevalence 6.7%). In a follow-up of 38.77 ± 29 months, 34 patients presented with one or more strokes; an incidence of 2.41/100 patient-years. Greater age [odds ratio (OR): 1.05; 95% confidence interval (CI): 1.01-1.09; P = 0.007], diabetes (OR: 2.29; 95% CI: 1.15-4.55; P = 0.018) and presence of atrial fibrillation (OR: 3.11; 95% CI: 1.53-6.32; P = 0.002) were independent predictors of stroke occurrence. Conclusions. The prevalence of ischaemic stroke is high at the commencement of dialysis, and its incidence is elevated in the course of follow-up. As with the general population, atrial fibrillation is an important factor predictive of ischaemic stroke, and as such, the clinical implication is that prophylactic anti-coagulation therapy needs to be considered for these individuals.