The Glomerular Disease Study and Trial Consortium: A Grassroots Initiative to Foster Collaboration and Innovation

Glomerular kidney disorders account for a significant proportion of chronic kidney disease and end-stage renal disease worldwide. Nevertheless, major obstacles make breakthrough progress in diagnosis and cure an ongoing challenge. Here we report the creation of a “grassroots” initiative that aims to provide new opportunities for nephrologists, pathologists, basic and clinical scientists, patients, and industry partners to collaborate in the field of glomerular kidney disease. Members of the medical community, including trainees, nephrologists, and nephropathologists, can participate in the open-access, Web-based, multidisciplinary clinical video case conferences, which provide “peer-to-peer” exchange of clinical and pathological expertise combined with a formal didactic curriculum. Participants can also join other aspects of the broader initiative. These include the participation in a multisite research study to facilitate enrollment of patients into a longitudinal clinical data and biorepository for glomerular kidney disorders. Items included in this prospective registry include the following: an ontology-based patient medical history, which is regularly updated; interval collection and storage of blood and urine samples; DNA collection; and a contact registry for patients who wish to participate in clinical trials. Participating sites and external scientists can leverage access to the database to pursue genetic, biomarker, epidemiological, and observational clinical effectiveness studies. Patients can independently sign up for a supplementary contact registry to participate in clinical trials if eligible. The broad spectrum of activities within this initiative will foster closer collaboration among trainees, practicing nephrologists, pathologists, and researchers, and may help to overcome some of the barriers to progress in the field of glomerular kidney disease. Keywords: disease registry, glomerular kidney disease, nephrology education, observational clinical studie

The CSL112-2001 trial: Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction

International audienceBACKGROUND:CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown.METHODS:CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 μmol/L in baseline serum creatinine for more than 24 hours, during the treatment period.RESULTS:A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial.CONCLUSIONS:These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy