Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A Sterol Panel for Multiple Rare Lipid Disorders: Validation and Application for Sitosterolemia, Cerebrotendinous Xanthomatosis and Smith-Lemli-Opitz Syndome

BACKGROUND. Disease-specific sterols accumulate in the blood of patients with several rare lipid disorders. Biochemical measurement of these sterols is important for correct diagnosis and sometimes monitoration of treatment. Existing methods to measure sterols in blood, particularly plant sterols, are often laborious and time consuming. Partly as a result, clinical access to sterol measurements are limited in many parts of the world. METHODS. A simple and rapid method to extract free sterols from human serum and quantitate their concentration using isotope-dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) without derivatization was developed. The method was designed to be “compatible” with routine workflows (eg. 96-well format) in a clinical lab and was extensively validated. Serum from 73 controls were analyzed and used to estimate the upper reference limits for sitosterol, campesterol, stigmasterol, desmosterol, 7-dehydrocholesterol (7DHC), lathosterol and cholestanol. Serum from patients with the rare lipid disorders sitosterolemia (n=7), Smith-Lemli-Optiz syndrome (SLOS; n=1) and cerebrotendinous xanthomatosis (CTX; n=1) were analyzed. RESULTS. All seven sitosterolemia patients were measured to have greatly elevated levels of free plant sterols (sitosterol, campesterol and stigmasterol) compared to the controls. The SLOS serum contained massively increased concentrations of 7DHC and an unidentified compound (likely 8-dehydrocholesterol). CTX serum contained greatly increased concentrations of cholestanol, as well as 7DHC and lathosterol. Spiking experiments indicated that the method is likely also useful in the diagnosis of desmosterolosis and lathosterolosis. CONCLUSION. The reported method is a relatively simple and fast method capable of quantitating diagnostically important sterols and differentiating patients with several rare lipid disorders from controls