The conventional forelimb grip strength test is a widely used method to assess skeletal muscle function in rodents; in this study, we modified this method to improve its variability and consistency. The modified test had lower variability among trials and days than the conventional test in young C57BL6 mice, especially by improving the variabilities in male. The modified test was more sensitive than the conventional test to detect a difference in motor function between female and male mice, or between young and old male mice. When the modified test was performed on male mice during the aging process, reduction of grip strength manifested between 18 and 24 months of age at the group level and at the individual level. The modified test was similar to the conventional test in detecting skeletal muscle dysfunction in young male dystrophic mice. Thus, the modified forelimb grip strength test, with its improved validity and reliability may be an ideal substitute for the conventional method.

D-Amino acids, the enantiomers of L-amino acids, are increasingly recognized as novel biomarkers. Although the amounts of D-amino acids are usually very trace in human, some of them have sporadically been detected in blood from patients with kidney diseases. This study examined whether multiple chiral amino acids would be associated with kidney functions, comorbidities, and prognosis of chronic kidney disease (CKD) by enantioselective analyses of all chiral amino acids with a micro-two-dimensional high-performance liquid chromatograph (2D-HPLC)-based analytical platform. 16 out of 21 D-amino acids were detected in plasma from 108 CKD patients in a longitudinal cohort. The levels of D-Ser, D-Pro, and D-Asn were strongly associated with kidney function (estimated glomerular filtration ratio), the levels of D-Ala and D-Pro were associated with age, and the level of D-Asp and D-Pro were associated with the presence of diabetes mellitus. D-Ser and D-Asn were significantly associated with the progression of CKD in mutually-adjusted Cox regression analyses; the risk of composite end point (developing to ESKD or death before ESKD) was elevated from 2.7- to 3.8-fold in those with higher levels of plasma D-Ser and D-Asn. These findings identified chiral amino acids as potential biomarkers in kidney diseases.

Significance Statement: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD remains a clinical challenge. Previous experimental studies showed that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. In a 2-year, open-label, randomized, controlled trial with a two-by-two factorial design, the authors investigated whether oral magnesium oxide or the oral carbon adsorbent AST-120 affected CAC progression in patients with stage 3−4 CKD with risk factors for CAC. In an interim analysis with 125 enrolled patients (96 of whom completed the trial), patients taking magnesium oxide experienced a significantly smaller percentage change in CAC score compared with controls (11.3% versus 39.5%). AST-120 was not associated with a similar significant slowing of CAC. Larger-scale trials are warranted to confirm these findings. Background: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. Methods: To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3−4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score. Results: We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group’s dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups. Conclusions: MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.

Background and objectives: Shorter or longer sleep duration and poor sleep quality are risk factors for numerous cardio-metabolic diseases, cardiovascular disease, and mortality in subjects with normal kidney function. The association of sleep duration and sleep quality with health outcomes in patients with CKD remains uncertain. Design, setting, participants, & measurements: A 4-year prospective cohort study in 17 nephrology centers in Japan, the CKD Japan Cohort (CKD-JAC) Study, assessed an association of self-reported sleep duration and sleep quality, on the basis of the Pittsburgh Sleep Quality Index (PSQI) questionnaire, with incidence of ESKD in 1601 patients with eGFR 10–59 ml/min per 1.73 m² using multivariable-adjusted Cox proportional hazards models. Results: Baseline sleep duration and PSQI global score for the 1601 patients were mean±SD 7.0±1.3 hours and median 4 (interquartile range, 3–7), respectively. Poor sleep quality (PSQI global score ≥6) was common (n=588 [37%]). During a median of 4.0 (2.6–4.3) years of the follow-up period, 282 (18%) patients progressed to ESKD. After adjusting for age, sex, eGFR, urinary albumin excretion, smoking status, body mass index, history of diabetes and cardiovascular disease, systolic BP, blockade of the renin-angiotensin system, use of hypnotics, and Beck depression inventory score, both shorter (≤5 hour) and longer (>8 hour) sleep duration were associated with ESKD (adjusted hazard ratios [95% confidence intervals] for ≤5.0, 5.1–6.0, 6.1–7.0, 7.1–8.0, and ≥8.0 hours were 2.05 [1.31 to3.21], 0.98 [0.67 to 1.44], 1.00 [reference], 1.22 [0.89 to 1.66], and 1.48 [1.01 to 2.16]), suggesting a U-shaped relationship between sleep duration and ESKD. PSQI global score ≥6 was also associated with incidence of ESKD (adjusted hazard ratios [95% confidence intervals] for PSQI global score ≤5 and ≥6 were 1.00 [reference] and 1.33 [1.03 to 1.71]). Conclusions: Shorter (≤5 hour) and longer (>8 hour) sleep duration and poor sleep quality (PSQI global score ≥6) were associated with ESKD in patients with CKD.