Efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists for renal and cardiovascular outcomes in patients with chronic kidney disease: a meta-analysis of randomized clinical trials.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD). Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software. Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = -2.83, 95% CI (-3.95, -1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = -0.41, 95% CI (-0.49, -0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875]. Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

Calculating osmotic pressure of glucose solutions according to ASOG model and measuring it with air humidity osmometry.

The osmotic pressure of glucose solution at a wide concentration range was calculated using ASOG model and experimentally determined by our newly reported air humidity osmometry. The measurements from air humidity osmometry were compared with the well-established freezing point osmometry and ASOG model calculations at low concentrations and with only ASOG model calculations at high concentrations where no standard experimental method could serve as a reference for comparison. Results indicate that air humidity osmometry measurements are comparable to ASOG model calculations at a wide concentration range, while at low concentrations freezing point osmometry measurements provide better comparability with ASOG model calculations.

Determining osmotic pressure of drug solutions by air humidity in equilibrium method.

OBJECTIVE: To establish a new osmotic pressure measuring method with a wide measuring range. METHOD: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution. The freezing point osmometry is used as a control. RESULTS: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method. CONCLUSION: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.

Calculating osmotic pressure of xylitol solutions from molality according to UNIFAC model and measuring it with air humidity osmometry.

The osmotic pressure of xylitol solution at a wide concentration range was calculated according to the UNIFAC model and experimentally determined by our newly reported air humidity osmometry. The measurements from air humidity osmometry were compared with UNIFAC model calculations from dilute to saturated solution. Results indicate that air humidity osmometry measurements are comparable to UNIFAC model calculations at a wide concentration range by two one-sided test and multiple testing corrections. The air humidity osmometry is applicable to measure the osmotic pressure and the osmotic pressure can be calculated from the concentration.