The long-term effect of a lung-ultrasound intervention on the risk for death, heart failure and myocardial infarction in dialysis patients

Extravascular lung water, a measure of fluid overload, is easily detected by lung ultrasound (US), a fast, easy-to-learn technique validated in dialysis patients [1]. Lung US is used for treatment monitoring in patients with decompensated heart failure [2, 3], and it is a powerful predictor of death and cardiovascular events in the dialysis population [4]. In the ‘LUng water by Ultra-Sound Guided Treatment (LUST) to Prevent Death and Cardiovascular Complications in High-Risk ESRD Patients with Cardiomyopathy’ trial (NCT02310061), a treatment strategy guided by lung US was not more effective than a usual care strategy in improving the primary endpoint of the study (a combination of death, heart failure and myocardial infarction) [5]. Since robust, long-term legacy effects of interventions targeting fluid volume status on major clinical outcomes in haemodialysis patients may emerge after the end of trials, we designed a post-trial, observational analysis extended up to 53 months (4.4 years). Since analyses by sex are important in clinical trials, as in the corresponding source trial, also in this study we performed effect modification analyses by sex and other major risk factors as a secondary endpoint

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study