The munber of chronic kidney disease (CKD) patients is increasing globally because kidney function is affected by aging and lifestyle habits. Malnutrition, muscle weakness, and a decline in ...activities of daily living (ADL) are often observed in elderly CKD patients and dialysis patients, and are related to their CKD prognosis and life prognoses. Chronic inflammation and atherosclerotic disease are associated with malnutrition. Because malnutrition and its related factors affect patients’ prognoses, it is necessary to identify and treat patients with malnutrition at an early stage. The state in which the stored protein and energy sources are reduced in CKD is called protein energy wasting (PEW). PEW is diagnosed on the basis of biochemical test findings such as hypoalbuminemia, unhealthy physique, and decreased muscle mass and dietary intake. For evaluating PEW, a complex nutritional index taking into account the pathophysiology specific to CKD patients is useful. Not only nutritional therapy but also exercise therapy is necessary to stop the vicious cycle associated with PEW and the decline in ADL.
Protein energy wasting (PEW) is a risk factor for death. However, the cutoff vales for PEW are not optimized for early identification of hemodialysis patients with malnutrition. We evaluated the ...prognosis of Japanese maintenance hemodialysis patients using nutritional indices optimized for them.
We analyzed data from a nation-wide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry to develop and validate a nutritional risk index (n = 48349, 48349, respectively). The association of nutritional factors with one-year death was tested using Cox proportional hazards models. Their cutoff levels were determined from the hazard ratios or receiver operating characteristic curves. Then, risk index was developed using scoring models.
Male was 61.4%; average age, 65.7±12.2 years; and diabetes mellitus, 32.8%. Four clinical factors were retained in the final model: low BMI (<20kg/m2), yes = 3, no = 0; low serum albumin level (young <3.7g/dL; old <3.5g/dL), yes = 4, no = 0; abnormal serum total cholesterol level, low (<130mg/dL) = 1, high (220≥mg/dL) = 2, no = 0; low serum creatinine level (young female, <9.7mg/dL; old female, <8.0mg/dL; young male, <11.6mg/dL; old male, <9.7mg/dL), yes = 4, no = 0. In the validation dataset, medium- and high-risk groups (total score 8 to 10; 11 or more) showed a higher risk of all-cause death than the low-risk group (0 to 7): medium-risk group (10.5%), hazard ratio adjusted for baseline characteristics 1.96 (95% confidence interval 1.77, 2.16); high-risk group (8.2%), 3.91 (3.57, 4.29). The medium- and high-risk groups also showed a higher risk of cardiovascular disease- and infection-caused deaths than the low-risk group.
We developed a new nutritional risk index for hemodialysis patients, which may detect patients with malnutrition with a high-risk of death.
Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, including heart ...failure. However, the mechanisms that regulate renal function responses to sodium glucose cotransporter 2 inhibition are not yet fully understood. We explored the renal protective effects of sodium glucose cotransporter 2 inhibition with empagliflozin, with a focus on glomerular hemodynamic effects and tubuloglomerular feedback using in vivo multiphoton microscopy imaging techniques.
C57BL/6 mice and spontaneously diabetic Ins2
mice were studied. The mice were treated with empagliflozin (20 mg·kg
·d
) and insulin for 4 weeks, and the single-nephron glomerular filtration rate was measured using multiphoton microscope. A neuronal nitric oxide synthase inhibitor (7-nitroindazole, 20 mg·kg
·d
) or a cyclooxygenase-2 inhibitor (SC58236, 6 mg/L), or an A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1 mg·kg
·d
) was administered to elucidate the mechanisms of tubuloglomerular feedback signaling and single-nephron glomerular filtration rate regulation.
The urinary excretion of adenosine, nitric oxide metabolites, and the prostanoid prostaglandin E2 was also quantified. The single-nephron glomerular filtration rate in the Ins2
group was higher than in controls (C57BL/6; 4.9±1.3 nL/min versus Ins2
; 15.8±6.8 nL/min) and lower in Ins2
/empagliflozin to 8.0±3.3 nL/min (P<0.01). In vivo imaging also revealed concomitant afferent arteriolar dilation (P<0.01) and increased glomerular permeability of albumin in the Ins2
group. Empagliflozin ameliorated these changes (P<0.01). Urinary adenosine excretion in the Ins2
/empagliflozin group was higher than in Ins2
(Ins2
; 3.4±1.4 nmol/d, Ins2
/empagliflozin; 11.2±3.0 nmol/d, P<0.05), whereas nitric oxide metabolites and prostaglandin E2 did not differ. A1 adenosine receptor antagonism, but not neuronal nitric oxide synthase or cyclooxygenase-2 inhibition, blocked the effect of empagliflozin on renal function. Empagliflozin increased urinary adenosine excretion and reduced hyperfiltration via afferent arteriolar constriction, effects that were abolished by A1 adenosine receptor blockade.
Adenosine/A1 adenosine receptor pathways play a pivotal role in the regulation of the single-nephron glomerular filtration rate via tubuloglomerular feedback mechanisms in response to sodium glucose cotransporter 2 inhibition, which may contribute to renal and cardiovascular protective effects reported in clinical trials.
Aim: Cardiovascular disease (CVD) is the second largest cause of death in Japanese women. Pregnancy and childbirth are events that put a strain on the cardiovascular system. When postpartum weight ...retention is insufficient, weight gain due to fat deposition during pregnancy might lead to obesity. Thus, we examined the effects of body mass index (BMI) in middle and older ages and the number of children on CVD and metabolic disorders.Methods: From the Tohoku Medical Megabank database, we used data from 32,000 women aged ≥ 50 years. This database contains obstetrical history, medical history, and laboratory data obtained once from 2013 to 2015.Results: The mean age of participants was 64.2 years, and 47.7% of women had two children. Compared with nulliparous women, those who had a higher number of children had higher BMI and systolic blood pressure. The prevalence of CVD was highest in obese class I (30 kg/m2 ≤ BMI) women with three or more children and the prevalence of hypertension was high in pre-obese (25 kg/m2 ≤ BMI ＜30 kg/m2) and obese class I women with children. Conversely, the prevalence of diabetes and proportion of women whose HbA1c values were ＞6.5% was highest in obese class I women with no children.Conclusion: In this study, we found that not only BMI but also the number of children influenced the health status of middle- and older-aged women, suggesting the importance of childbirth history in the health management of women.
Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, ...there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM.
DEFENCE is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial. Between October 2015 and August 2016, 80 T2DM patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0 and <8.0%, n = 80) were enrolled and randomized to receive either 1500 mg/day metformin (the metformin group, n = 40), or 750 mg/day metformin supplemented with 5 mg/day dapagliflozin (the dapagliflozin group, n = 40), for 16 weeks. The primary endpoint was a change in flow-mediated dilation (FMD) from baseline to the end of the 16-week treatment period. The secondary outcomes include changes in indexes of glycemic control, lipid metabolism, and oxidative stress, body composition, and safety evaluation.
Although FMD tended to improve only in the dapagliflozin group, ΔFMD was comparable between the two groups. Analysis of patients with HbA1c >7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P < 0.05). HbA1c, fasting plasma glucose, plasma glucagon, and body weight significantly decreased in both groups. Interestingly, urine 8-hydroxy-2'-deoxyguanosin, a biomarker of oxidative stress, was significantly lower in the dapagliflozin group than metformin group at 16 weeks (P < 0.001).
Dapagliflozin add-on therapy to metformin for 16 weeks improved endothelial function, as assessed by FMD, in patients with inadequately controlled early-stage T2DM. Improvement in oxidative stress may contribute to the improvement in FMD. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000018754).
Background
It is known that sarcopenia is related to malnutrition-inflammation-atherosclerosis (MIA) syndrome and is an important problem in dialysis patients. The notion of frailty includes various ...physical, psychological, and social aspects. Although it has been reported that sarcopenia is associated with poor prognosis in patients with hemodialysis, reports on peritoneal dialysis (PD) patients are rare. In this study, we examined the morbidity and mortality of sarcopenia and frailty in PD patients. We also investigated the MIA-related factors.
Methods
We evaluated 119 patients cross-sectionally and longitudinally. The Asian Working Group for Sarcopenia criteria and the Clinical Frailty Scale (CFS) were used to diagnose sarcopenia and frailty. The primary outcome is all-cause mortality with sarcopenia and frailty. The secondary outcome is the relationship between various MIA-related factors.
Results
Morbidity of sarcopenia and frailty in PD patients was 8.4% and 10.9%, respectively. Old age, high values of Barthel Index, Charlson Comorbidity Index, CFS, and low values of body mass index (BMI), muscle strength, muscle mass, and slow walking were associated with sarcopenia. Interleukin-6, albumin, and prealbumin were significantly correlated with muscle mass. During follow-up, the presence of sarcopenia or frailty was associated with the risk of mortality. In multivariate analysis, CFS was related to the mortality rate of PD patients.
Conclusions
The presence of sarcopenia or frailty was associated with a worse prognosis.
Appropriate maxillofacial growth and development evaluation is important for effective orthodontic treatment. Growth evaluation is based on physiological age determined by individual development, but ...not chronological age. One strategy for determining physiological age is using the cervical vertebral bone age.
This study aimed to clarify the standard size of the upper and lower jawbones in Japanese patients using the cervical vertebral maturation stages (CVMS) as an index and clarify the growth pattern. And to use the cervical spine age as a diagnostic aid in orthodontic treatment.
Random sampling was performed from the outpatients who visited the Orthodontics department, Tokyo Medical and Dental University Dental Hospital, and 400 patients were enrolled before treatment. Lateral cephalometric radiographs were obtained to measure the height and length of the mandible and the maxilla length with cephalometric analysis. Standard values were calculated for each cervical-spine-age group to analyze changes during mandibular and maxillary growth. Furthermore, we compared the differences between males and females. The Kruskal-Wallis test was used to compare cervical-spine-age groups, and the Steel-Dwass test was used for multiple comparisons. The reliability of CVMS was confirmed by calculating the weighted kappa coefficient (κ).
κ for the degree of intra-evaluator agreement and the degree of the inter-evaluator agreement were calculated, and both indicated almost perfect agreement. We found that the distance between the anterior nasal spine (ANS) and posterior nasal spine (PNS) (i.e., ANS-PNS) increased significantly between CVMS II and CVMS III in males. The distance between Articulare (Ar) and Gonion (Go) (i.e., Ar-Go) and the distance between Go and Pogonion (Pog) (i.e., Go-Pog) increased significantly between CVMS III and CVMS IV in males.
The findings suggested that CVMS is a reliable indicator of the growth stage of the maxilla and mandible.
Identifying progressive early chronic kidney disease (CKD) patients at a health checkup is a good opportunity to improve their prognosis. However, it is difficult to identify them using common health ...tests. This worksite-based cohort study for 7 years in Japan (n = 7465) was conducted to evaluate the progression of CKD. The outcome was aggravation of the KDIGO prognostic category of CKD 7 years later. The subjects were male, 59.1%; age, 50.1 ± 6.3 years; and eGFR, 79 ± 14.4 mL/min/1.73 m
. The number of subjects showing CKD progression started to increase from 3 years later. Vector analysis showed that CKD stage G1 A1 was more progressive than CKD stage G2 A1. Bayesian networks showed that the time-series changes in the prognostic category of CKD were related to the outcome. Support vector machines including time-series data of the prognostic category of CKD from 3 years later detected the high possibility of the outcome not only in subjects at very high risks but also in those at low risks at baseline. In conclusion, after the evaluation of kidney function at a health checkup, it is necessary to follow up not only patients at high risks but also patients at low risks at baseline for 3 years and longer.
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