BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Background Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials. Methods SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD. Discussion Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD. Trial registration Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653.

Background and Aims Cognitive impairment is very common in dialysis patients, with negative effects on quality of life and mortality. In neurodegenerative conditions (Alzheimer, Parkinson) a gut-brain axis has been identified; however, there is no information about the relationship of gut microbiota alterations and presence of cognitive impairment in chronic kidney disease. The aim was to associate the gut microbiota profile with the cognitive function in patients on automated peritoneal dialysis (APD). Method Cross-sectional study in 39 APD patients; those with visual or mental disabilities, psychiatric or neurodegenerative diseases, inflammatory causes of ESRD, with active infections (including peritonitis), on anti-inflammatory drugs or antibiotics, were excluded. All patients had a clinical, biochemical, nutritional and dialysis adequacy evaluation, and were classified according to the presence of cognitive impairment using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected and immediately stored at -80 ºC. DNA extraction was performed with Quick-DNA Fecal/Soil Microbe Miniprep Kit (Zymo Research). Subsequently, V3 and V4 regions of 16S rRNA were sequenced using illumina platform. Statistical analysis: Student t test and χ2 were used to compare quantitative and qualitative variables, respectively. Quantitative Insights Into Microbial Ecology (QIIME) pipeline and Linear Discriminant Analysis Effect Size (LEfSe) were employed for bioinformatic analysis. Results Eighty-two percent of subjects were male, mean age 47 ± 24 years, and dialysis vintage 11 (7-48) months. Sixty-four percent of patients had cognitive impairment. Patients with cognitive impairment were significantly older (53 ± 16 vs 38 ± 14, p=0.006), had higher frequency of diabetes mellitus (56% vs 21%, p=0.04), and had lower creatinine concentrations (11.3 ± 3.7 vs 14.9 ± 5.4, p=0.02) compared to patients with normal cognitive function. No differences were found in other biochemical, nutritional or dialysis adequacy variables. A total of 38,083 sequences per patient were obtained after the microbiome analysis. LEfSe analysis showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter, and Anaerotruncus in patients with cognitive impairment. In contrast, patients without cognitive impairment were characterized by Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) &gt; 2.5; p &lt; 0.05). Conclusion Cognitive impairment was present in two-thirds of these APD patients. Odoribacter and Anaerotruncus were significantly more abundant in patients with cognitive impairment than in those with normal function. Such gut bacteria might enhance cognitive impairment as have been described to increase the uremic toxin production and activation of inflammatory pathways in the central nervous system. This is the first study providing evidence than brain and behavior might be influenced by the gut-brain axis in dialysis patients.

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Objectives: This study was conducted with the purpose of search evidence in terms of the efficacy and safety that to demonstrated advantages of any of the renal replacement therapy in terms of peritoneal dialysis (PD), hemodialysis (HD) and kidney transplant (KT) , used in patients with chronic kidney failure. Methods: The systematic review was performed BY Cochrane Methodology in PubMed/Medline, Cochrane Library, and LILAC's. Only observational studies were included in adult patients with chronical kidney failure and that were under one of the renal replacements treatments were included. STROBE tool was used to evaluate the quality of these studies. Results: Of the 4,472 studies, only 8 observational studies fulfil the inclusion criteria. From these only 6 studies compared peritoneal dialysis vs haemodialysis, from which , it was proven that patients with PD show better comorbidities in comparison with those who are under treatment with haemodialysis (diabetes, cardiovascular and cardiac diseases One additionally study evaluates the quality of life in all substitution therapies , where it was reported that patients who received KT showed a bigger satisfaction with the therapy (4.85) in comparison with PD (3.59) and HD (4.59). On the other hand, the las study evaluates the survival during 18 months between those three treatments, being better in KT (96.960.031) vs DP (9460.024) vs HD (8360.093). Population consist of: 66,190 patients that were distributed in PD 21,163, HD 44,904 and KT 123. Evaluated in average of 61 months for HD and 50 months for PD. Conclusions: While evaluating only observational studies, these demonstrate that KT could be the election therapy in patients with chronic kidney disease, However, more evidence is necessary and with higher quality level in order to sustain the research.