The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review.

BACKGROUND: The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. DATA SOURCES: We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: "Atypical Hemolytic Uremic Syndrome," "aHUS," "eculizumab," "Pediatrics," "Pediatric," "Child," "Children," "Adolescent." STUDY ELIGIBILITY CRITERIA: The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. PARTICIPANTS AND INTERVENTIONS: The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. STUDY APPRAISAL: For quality assessment, we used the Newcastle-Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. RESULTS: The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. LIMITATIONS: The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. CONCLUSIONS: Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42021266255.

Evaluation of insertion/deletion (I/D) polymorphisms of ACE gene and circulating levels of angiotensin II in congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II (Ang II) and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene and the circulating levels of Ang II are associated with any CAKUT phenotype or CAKUT in general. METHODS AND RESULTS: Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association was detected between ACE I/D polymorphism and CAKUT and UPJO, VUR, and MCDK phenotypes. In a subset of 80 CAKUT patients and 80 controls, plasma levels of Ang II were measured. No significant differences were found between CAKUT patients and controls, even in regard to comparisons of UPJO, VUR and MCDK with control group. CONCLUSION: Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms nor with differences in plasma levels of Ang II in this Brazilian pediatric population.