長田 太助

We evaluated the skeletal muscle loss in hemodialysis (HD) patients by bioelectrical impedance analysis (BIA) and handgrip strength test. Thirty-four HD patients and 16 healthy subjects (control group) were measured for skeletal muscle mass normalized as the skeletal muscle mass index (SMI), calculated as skeletal muscle mass (kg)/height (m)(2) using a tetrapolar bioelectrical impedance plethysmograph. Handgrip strength test was also performed using a hand dynamometer in both groups. In HD patients, the associations of SMI and handgrip strength with age, sex, HD conditions, and HD parameters such as body mass index (BMI), single-pool Kt/V (spKt/V), normalized protein catabolic rate (nPCR), creatinine generation rate (CGR) and serum albumin level (Alb) were investigated. SMI of HD patients (4.58 +/- 0.95kg/m(2)) was significantly lower than that of the control group (5.55 +/- 0.80kg/m(2), P<0.01). The handgrip strength of HD patients (19.9 +/- 7.74kg) was also significantly lower than that of the control group (33.0 +/- 8.94kg, P<0.01). In HD patients, HD duration was associated with both SMI and handgrip strength. Among HD parameters, spKt/V was negatively associated with both SMI and handgrip strength, BMI and Alb were positively associated with SMI, while nPCR and CGR were associated with neither SMI nor handgrip strength. HD duration independently contributed to skeletal muscle loss and the value of spKt/V may be affected by skeletal muscle loss in HD patients.

Inflammation plays a crucial role in the pathophysiologicat characteristics of chronic kidney disease; however, the inflammatory mechanisms underlying the chronic kidney disease process remain unclear. Recent evidence indicates that sterile inflammation triggered by tissue injury is mediated through a muttiprotein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in the development of chronic kidney disease using a murine unilateral ureteral obstruction (UUO) model. Inflammasome-related molecules were up-regulated in the kidney after UUO. Apoptosis-associated speck-like protein containing a caspase recruitment domain deficiency significantly reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, and improved subsequent renal injury and fibrosis. Furthermore, apoptosis-associated speck-like protein containing a caspase recruitment domain was specifically up-regulated in collecting duct (CD) epithelial cells of the UUO-treated kidney. In vitro experiments showed that extracellular adenosine triphosphate (ATP) induced inflammasome activation in CD epithelial cells through P2X(7)-potassium efflux and reactive oxygen species dependent pathways. These results demonstrate the molecular basis for the inflammatory response in the process of chronic kidney disease and suggest the CD inflammasome as a potential therapeutic target for preventing chronic kidney disease progression.

Because endothelial nitric oxide synthase (eNOS) has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177) in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172) and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

To determine whether vigorous and moderate physical activity volumes are associated with skeletal muscle loss and chronic kidney disease-mineral and bone disorder (CKD-MBD) in hemodialysis (HD) patients. Skeletal muscle index (SMI) was measured using a bioelectrical impedance plethysmograph, and grip strength using a hand dynamometer, in 32 HD patients and 16 healthy controls. In HD patients, bone density was measured using digital image processing, and serum bone metabolism markers were measured as surrogate markers for CKD-MBD. Vigorous and moderate physical activity volumes of HD patients were measured using an activity monitor for 1 week, and associations between vigorous and moderate physical activity volumes and SMI, grip strength, and surrogate markers for CKD-MBD were investigated. SMI of HD patients (4.60 +/- A 0.98 kg/m(2)) was significantly lower than that of controls (5.55 +/- A 0.80 kg/m(2), p < 0.01). Grip strength of HD patients (19.9 +/- A 7.74 kg) was also significantly lower than that of controls (33.0 +/- A 8.94 kg, p < 0.01). In HD patients, vigorous and moderate physical activity volumes were significantly positively associated with SMI (beta = 0.309, p = 0.023) but not grip strength (beta = 0.231, p = 0131) after adjustment for age, sex, and HD duration. They were not associated with bone density (beta = 0.106, p = 0.470) or any markers of bone metabolism. Vigorous and moderate physical activity volumes were positively associated with skeletal muscle mass but not skeletal muscle strength or surrogate markers for CKD-MBD.

Background: The appropriate exercise counseling for chronic kidney disease (CKD) patients is crucial to improve their prognosis. There have been few studies about exercise counseling by primary care physicians for CKD patients. We investigated primary care physicians' exercise counseling practices for CKD patients and the association of these physicians' own exercise habits with exercise counseling. Methods: The population of this cross-sectional study was 3310 medical doctors who graduated from Jichi Medical University from 1978 to 2012. The study instrument was a self-administered questionnaire that was mailed in August 2012 to investigate their age class specialtynm workplace exercise habits and practices of exercise counseling for CKD. Results: 581 (64.8%) medical doctors practiced the management of CKD among a total of 933 responses. These 581 medical doctors were defined as CKD primary care physicians and their answers were analyzed. CKD primary care physicians' own exercise habits (frequencies and intensities) were as follows: frequencies: daily 71 (12.1%) >= 2-3 times/week 154 (26.5%) >= 1 time/week 146 (25.1%) and <= 1 time/month 176 (30.2%) intensities: high (>= 6 Mets) 175 (30.1%) moderate (4-6 Mets) 132 (22.7%) mild (3-4 Mets) 188 (32.3%) very mild (< 3 Mets) 47 (8.1%) and none 37 (6.4%). The CKD primary care physicians' exercise recommendation levels for CKD patients were as follows: high 31 (5.3%) moderate 176 (29.7%) low 256 (44.0%) and none 92 (15.8%). The CKD primary care physicians' exercise recommendations for CKD patients were significantly related to their own exercise frequency (p < 0.001) but they were not related to their age specialty workplace or exercise intensity. Conclusions: CKD primary care physicians' exercise recommendation level for CKD patients was limited. In addition CKD primary care physicians' own exercise habits influenced the exercise counseling for CKD patients. The establishment of guidelines for exercise by CKD patients and their dissemination among primary care physicians are needed. (University Hospital Medical Information Network Clinical Trial Registry. number UMIN000011803. Registration date Sep/19/2013)