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The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse outcome. TMA is described as the association of microangiopathic hemolytic anemia, thrombocytopenia, and an organ injury, frequently the kidney. This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55 days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had rapid improvement in hematological parameters, and dialysis was discontinued 25 days after the first dose. Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS). Twenty patients who received eculizumab with SLE and/or APS have been published to date: 11 were female and mean age at presentation was 31 years. Seven out of the 20 patients presented only SLE, 5 patients only APS and 8 patients both SLE and APS. Eighteen patients underwent plasma exchange, with a mean of 20 (4-120) sessions per patient. Thirteen patients received rituximab. Hematological response was evident in 100% and kidney recovery in 85% of patients. The terminal complement blockade with eculizumab is an optional treatment for patients with SLE and/or APS presenting TMA and refractory to current immunosuppression therapies. Genetic testing may help recognize patients with aHUS and SLE/APS and therefore help to determine length of treatment with eculizumab.

The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

IntroductionThe treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS.MethodsDescription of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation).ResultsSeven cases were outlined: five of therapeutic use and two, prophylactic. From the five cases of therapeutic use, there was improvement of the thrombotic microangiopathy in the 48 hours following the start of the drug and no patient experienced relapse during an average follow-up of 21 months in the continuous use of eculizumab (minimum of 6 and maximum of 42 months). One patient died at 6 months, due to Aspergillus infection. From the two cases of prophylactic use, one patient experienced relapsed thrombotic microangiopathy after 4 months and another patient remained asymptomatic after 16 months of follow-up, both on chronic treatment.DiscussionThe therapeutic use of eculizumab showed to be effective, with improvement of the microangiopathy parameters and persisting up to the end of the follow-up, without relapses. The additional risk of immunosuppression, leading to opportunistic infections, was well tolerated. The prophylactic use showed to be effective and safe; however, the doses and intervals should be individualized in order to avoid relapsed microangiopathy, especially in patients with factor H mutation.

The Brazilian collaborative registry for pediatric renal transplantation began in 2004 as a multicenter initiative aimed at analyzing, reporting, and disseminating the results of pediatric renal transplantation in Brazil. Data from all pediatric renal transplants performed from January 2004 to May 2018 at the 13 participating centers were analyzed. A total of 2744 pediatric renal transplants were performed in the thirteen participating centers. The median age at transplantation was 12.2 years, with the majority being male recipients (56%). The main underlying diseases were CAKUT (40.5%) and glomerulopathy (28%). 1981 (72%) of the grafts were from deceased donors (DD). Graft survival at one year (censored by death) was 94% in the live donor group (LD) and 91% in the DD group (log‐rank test P < 0.01). The patient’s survival at one and 5 years was 97% and 95% for the LD group and 96% and 93% for the DD group (log‐rank test P = 0.02). The graft loss rate was 19% (n = 517), more frequently caused by vascular thrombosis (n = 102) and chronic graft nephropathy (n = 90). DD recipients had 1.6 (1.0‐2.2) times greater chance of death and 1.5 (1.2‐1.8) times greater chance of graft loss compared to LD recipients. The mortality rate was 5.4% (n = 148), mainly due to infection (n = 69) and cardiovascular disease (n = 28). The results of this collaborative pediatric renal transplant record are comparable to other international registries, although we still have a high infection rate as a cause of death.