Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose-response, phase 2/3 study.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. METHODS: This phase 2/3, randomized, double-blind, placebo-controlled, dose-response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1- ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK+ over 48 h. The proportion of patients with normokalemia (sK+ 3.5-5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. RESULTS: Overall, 103 patients (mean age, 73.2 years; range 50-89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK+ change from 0 to 48 h versus placebo was - 0.00261 (SZC 5 g) and - 0.00496 (SZC 10 g; both P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious AEs were reported. Hypokalemia (sK+ < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported. CONCLUSION: SZC is effective and well tolerated in Japanese patients with hyperkalemia.

Glycated albumin predicts the risk of mortality in type 2 diabetic patients on hemodialysis: evaluation of a target level for improving survival.

Glycated albumin (GA) is considered a more reliable marker than glycated hemoglobin (HbA1c) for monitoring glycemic control, particularly in diabetic hemodialysis patients. We investigated the associations of GA, HbA1c, and random serum glucose levels with survival, and evaluated possible targets for improving survival in diabetic hemodialysis patients. In this prospective, longitudinal, observational study, we enrolled 90 diabetic hemodialysis patients across six dialysis centers in Japan. The median duration of follow-up was 36.0 months (mean follow-up, 29.8 months; range, 3-36 months). There were 11 deaths during the observation period. GA was a significant predictor for mortality (hazard ratio, 1.143 per 1% increase in GA; 95% confidence interval, 1.011-1.292; P = 0.033), whereas HbA1c and random glucose levels were not predictors for mortality. Receiver operating characteristics curve analysis showed that the cutoff value of GA for predicting the risk of mortality was 25%. In the Kaplan-Meier analysis, the cumulative survival rate was significantly greater in patients with GA ≤ 25% than in patients with GA >25%. GA predicted the risk of all-cause and cardiovascular mortality in diabetic hemodialysis patients. Our results suggest that GA ≤ 25% is an appropriate target for improving survival in diabetic hemodialysis patients.

Cyclic AMP inhibits stretch-induced overexpression of fibronectin in glomerular mesangial cells.

Glomerular hypertension is proposed to play an important role in the progression of various glomerular diseases. Glomerular mesangial cells are considered to be exposed to the stretch stress due to glomerular hypertension and are found to produce the excess amount of extracellular matrix (ECM) proteins including fibronectin when exposed to the mechanical stretch. Herein, we provide the evidence that cAMP-generating agents inhibit the stretch-induced overexpression of fibronectin through the inhibition of the stretch-induced activation of mitogen-activated protein kinases (MAPKs) in protein kinase-A-dependent manner. We also found that the mechanical stretch enhanced the binding of nuclear extracts to activator protein-1 (AP-1)-like sequences in the promoter region of rat fibronectin gene and this enhancement was also prevented by the cAMP-generating agent. These results indicate that the agents, which activate cAMP/protein kinase-A axis, may work protectively against the injury from glomerular hypertension in mesangial cells.