How Does GSK-3 inhibitor Function?

73 m2 compared with patients with a higher eGFR (10.3 versus 6.4%); importantly a decrease of eGFR was seen in 17% of patients in the spironolactone and 7% in the placebo group. Such a decrease of eGFR increased the adjusted risk of death by a factor of 1.9 in the placebo group, but an increase of risk was not seen in the spironolactone group. Remarkably, the absolute benefit from spironolactone was greatest in patients with reduced eGFR! Although worsening renal function was associated with a negative prognosis, the mortality benefit of spironolactone was still demonstrable. The Chronic Renal Impairment study in Birmingham studied 115 non-diabetic CKD patients with an eGFR of 30�C89 mL/min/1.73 m2 on spironolactone plus RAS blockade; they were followed for 40 weeks; despite rigorous ankyrin follow-up, Quisinostat supplier S-K+ values >5.5 mmol/L were seen in ?10% [51]. In a post hoc analysis of the EPHESUS trial [49], the following items were independent predictors of serum K+ > 6 mmol/L: eGFR 4.3 mmol/L and prior use of anti-arrhythmics. In a post hoc analysis, the decrease in eGFR was higher in the eplerenone group compared with placebo (P 68 years, smoking, LVEF find more provided still a mortality benefit despite the association of a reduced GFR with a negative prognosis. Novel strategies to interfere with mineralocorticoid receptor-mediated effects On the horizon are novel compounds: on the one hand, substances inhibiting mineralocorticoid receptors [52], e.g. PF-03882845 with high affinity and selectivity for the mineralocorticoid receptor. In animal experiments, it was more potent than eplerenone or BR-4628 [53, 54]. Recently, another non-steroidal mineralocorticoid receptor antagonist has been developed, BAY 94-8862, with greater selectivity compared with spironolactone and stronger mineralocorticoid receptor binding affinity compared with eplerenone. It is currently evaluated in a randomized double-blind study of patients with chronic heart failure and mild-to-moderate CKD [55].