Association of Serum Phosphate with Low Handgrip Strength in Patients with Advanced Chronic Kidney Disease

Muscle wasting and hyperphosphatemia are becoming increasingly prevalent in patients who exhibit a progressive decline in kidney function. However, the association between serum phosphate (Pi) level and sarcopenia in advanced chronic kidney disease (CKD) patients remains unclear. We compared the serum Pi levels between advanced CKD patients with (n = 51) and those without sarcopenia indicators (n = 83). Low appendicular skeletal muscle mass index (ASMI), low handgrip strength, and low gait speed were defined per the standards of the Asian Working Group for Sarcopenia. Mean serum Pi level was significantly higher in advanced CKD patients with sarcopenia indicators than those without sarcopenia indicators (3.88 ± 0.86 vs. 3.54 ± 0.73 mg/dL; p = 0.016). Univariate analysis indicated that serum Pi was negatively correlated with ASMI, handgrip strength, and gait speed. Multivariable analysis revealed that serum Pi was significantly associated with handgrip strength (standardized β = −0.168; p = 0.022) and this association persisted even after adjustments for potential confounders. The optimal serum Pi cutoff for predicting low handgrip strength was 3.65 mg/dL, with a sensitivity of 82.1% and specificity of 56.6%. In summary, low handgrip strength is common in advanced CKD patients and serum Pi level is negatively associated with handgrip strength.     

Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia

Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.     

Sarcopenia and Mortality in Older Hemodialysis Patients

(1) Sarcopenia is a progressive loss of skeletal muscle mass and strength. The aim of this study was to determine the association of sarcopenia, defined according to the Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria, with mortality at 24 months in very elderly hemodialysis patients. (2) A prospective study was conducted in 60 patients on chronic hemodialysis who were older than 75 years. Sarcopenia was diagnosed according to EWGSOP2 criteria. Additionally, clinical, anthropometric and analytical variables and body composition by bioimpedance were assessed. The date and cause of death were recorded during 2 years of follow-up. (3) Among study participants, 41 (68%) were men, the mean age 81.85 ± 5.58 years and the dialysis vintage was 49.88 ± 40.29 months. The prevalence of probable sarcopenia was 75% to 97%, depending on the criteria employed: confirmed sarcopenia ranged from 37 to 40%, and severe sarcopenia ranged from 18 to 37%. A total of 30 (50%) patients died over 24 months. Sarcopenia probability variables were not related to mortality. In contrast, sarcopenia confirmation (appendicular skeletal muscle mass, ASM) and severity (gait speed, GS) variables were associated with mortality. In multivariate analysis, the hazard ratio (95% confidence interval) for all-cause death was 3.03 (1.14–8.08, p = 0.028) for patients fulfilling ASM sarcopenia criteria and 3.29 (1.04–10.39, p = 0.042) for patients fulfilling GS sarcopenia criteria. (4) The diagnosis of sarcopenia by EWGSOP2 criteria is associated with an increased risk of all-cause death in elderly dialysis patients. Specifically, ASM and GS criteria could be used as mortality risk markers in elderly hemodialysis patients. Future studies should address whether the early diagnosis and treatment of sarcopenia improve outcomes.     

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.     

Preserved Skeletal Muscle Mitochondrial Function,Redox State,Inflammation and Mass in Obese Mice with Chronic Heart Failure

Background: Skeletal muscle (SM) mitochondrial dysfunction, oxidative stress, inflammation and muscle mass loss may worsen prognosis in chronic heart failure (CHF). Diet-induced obesity may also cause SM mitochondrial dysfunction as well as oxidative stress and inflammation, but obesity per se may be paradoxically associated with high SM mass and mitochondrial adenosine triphosphate (ATP) production, as well as with enhanced survival in CHF. Methods: We investigated interactions between myocardial infarction(MI)-induced CHF and diet-induced obesity (12-wk 60% vs. standard 10% fat) in modulating gastrocnemius muscle (GM) mitochondrial ATP and tissue superoxide generation, oxidized glutathione (GSSG), cytokines and insulin signalling activation in 10-wk-old mice in the following groups: lean sham-operated, lean CHF (LCHF), obese CHF (ObCHF; all n = 8). The metabolic impact of obesity per se was investigated by pair-feeding ObCHF to standard diet with stabilized excess body weight until sacrifice at wk 8 post-MI. Results: Compared to sham, LCHF had low GM mass, paralleled by low mitochondrial ATP production and high mitochondrial reative oxygen species (ROS) production, pro-oxidative redox state, pro-inflammatory cytokine changes and low insulin signaling (p < 0.05). In contrast, excess body weight in pair-fed ObCHF was associated with high GM mass, preserved mitochondrial ATP and mitochondrial ROS production, unaltered redox state, tissue cytokines and insulin signaling (p = non significant vs. Sham, p < 0.05 vs. LCHF) despite higher superoxide generation from non-mitochondrial sources. Conclusions: CHF disrupts skeletal muscle mitochondrial function in lean rodents with low ATP and high mitochondrial ROS production, associated with tissue pro-inflammatory cytokine profile, low insulin signaling and muscle mass loss. Following CHF onset, obesity per se is associated with high skeletal muscle mass and preserved tissue ATP production, mitochondrial ROS production, redox state, cytokines and insulin signaling. These paradoxical and potentially favorable obesity-associated metabolic patterns could contribute to reported obesity-induced survival advantage in CHF.     

Low Serum 25-Hydroxyvitamin D Levels Are Related to Frailty and Sarcopenia in Patients with Chronic Liver Disease

Low vitamin D status is related to frailty and/or sarcopenia in elderly individuals. However, these relationships are unclear in patients with chronic liver disease (CLD). This study aimed at exploring the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and frailty or sarcopenia in 231 patients with CLD. Frailty was determined based on five factors (weight loss, low physical activity, weakness, slowness, and exhaustion). Sarcopenia was diagnosed by applying the Japan Society of Hepatology criteria. The patients were classified into three groups according to baseline 25(OH)D levels: low (L), intermediate (I), and high (H) vitamin D (VD) groups. Of the 231 patients, 70 (30.3%) and 66 (28.6%) had frailty and sarcopenia, respectively. The prevalence rate of frailty and sarcopenia significantly increased stepwise with a decline in the vitamin D status. The L-VD group showed the highest prevalence rates of frailty and sarcopenia (49.1% (28/57), p < 0.001 for both), whereas the H-VD group showed the lowest prevalence rates of frailty (15.3% (9/59)) and sarcopenia (18.6% (11/59)) (p < 0.001 for both). Multivariate analysis identified serum 25(OH)D levels as a significant independent factor related to frailty and sarcopenia. Serum 25(OH)D levels significantly correlated with handgrip strength, skeletal muscle mass index, and gait speed. In conclusion, low serum vitamin D level, especially severe vitamin D deficient status, is closely related to frailty and sarcopenia in patients with CLD.     

Importance of Considering Malnutrition and Sarcopenia in Order to Improve the QOL of Elderly Hemodialysis Patients in Japan in the Era of 100-Year Life

In the current aging society of Japan, malnutrition and resultant sarcopenia have been widely identified as important symptomatic indicators of ill health and can cause impairments of longevity and quality of life in older individuals. Elderly individuals are recommended to have sufficient calorie and protein intake so as to enjoy a satisfactory quality of life, including maintaining activities of daily living in order to avoid emaciation and sarcopenia. The prevalence of emaciation and sarcopenia in elderly hemodialysis (HD) patients in Japan is higher than in non-HD elderly subjects due to the presence of malnutrition and sarcopenia associated with chronic kidney disease (CKD). Furthermore, comorbidities, such as diabetes and osteoporosis, induce malnutrition and sarcopenia in HD patients. This review presents findings regarding the mechanisms of the development of these early symptomatic conditions and their significance for impaired QOL and increased mortality in elderly HD patients.     

高通量血液透析用于慢性肾病患者治疗中的效果分析

目的:探究高通量血液透析用于慢性肾病患者治疗中的临床疗效.方法:选择2017年10月~2018年12月在本院进行常规维持性血液透析治疗3个月的60例慢性肾病患者作为此次研究对象,对本组患者给予高通量血液透析,连续治疗6个月,观察本组患者治疗前后P、PTH、Alb、Hb、TC以及血压指标,对比临床治疗效果.结果:患者治疗后P、PTH、Alb、Hb、TC以及血压指标显著优于治疗前,且差异具有统计学意义(P<0.05).结论:针对慢性肾病患者,临床给予高通量血液透析治疗效果显著,可在一定程度上改善患者临床症状,减少出现并发症的危险.     

Nutritional Predictors of Mortality after 10 Years of Follow-Up in Patients with Chronic Kidney Disease at a Multidisciplinary Unit of Advanced Chronic Kidney Disease

Nutritional monitoring in advanced chronic kidney disease (ACKD) units provides personalized care and improves clinical outcomes. This study aimed to identify mortality risk factors in chronic kidney disease (CKD) patients on nutritional follow-up in the multidisciplinary ACKD unit. A retrospective cross-sectional observational study was conducted in 307 CKD patients’ stage 3b, 4–5 followed-up for 10 years. Clinical and nutritional monitoring was performed by malnutrition-inflammation score (MIS), biochemical parameters (s-albumin, s-prealbumin, and serum C-reactive protein (s-CRP), body composition measured by bioelectrical impedance analysis (BIA), anthropometry, and handgrip strength measurements. The sample was classified into non-survivors, survivors, and censored groups. Of the 307 CKD patients, the prevalence of protein-energy wasting (PEW) was 27.0% using MIS > 5 points, s-CRP > 1 mg/dL was 19.20%, and 27.18% died. Survivors had higher significant body cell mass (BCM%) and phase angle (PA). Survival analyses significantly showed that age > 72 years, MIS > 5 points, s-prealbumin ≤ 30 mg/dL, PA ≤ 4°, and gender-adjusted handgrip strength (HGS) were associated with an increased risk of mortality. By univariate and multivariate Cox regression, time on follow-up (HR:0.97), s-prealbumin (HR:0.94), and right handgrip strength (HR:0.96) were independent predictors of mortality risk at 10 years of follow-up in the ACKD unit. Nutritional monitoring in patients with stage 3b, 4–5 CKD helps to identify and treat nutritional risk early and improve adverse mortality prognosis.     

Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca²⁺) homeostasis and cause alterations of multiple Ca²⁺-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca²⁺-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca²⁺ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.     

Optimal Protein Intake in Pre-Dialysis Chronic Kidney Disease Patients with Sarcopenia: An Overview

Multi-factors, such as anorexia, activation of renin-angiotensin system, inflammation, and metabolic acidosis, contribute to malnutrition in chronic kidney disease (CKD) patients. Most of these factors, contributing to the progression of malnutrition, worsen as CKD progresses. Protein restriction, used as a treatment for CKD, can reduce the risk of CKD progression, but may worsen the sarcopenia, a syndrome characterized by a progressive and systemic loss of muscle mass and strength. The concomitant rate of sarcopenia is higher in CKD patients than in the general population. Sarcopenia is also associated with mortality risk in CKD patients. Thus, it is important to determine whether protein restriction should be continued or loosened in CKD patients with sarcopenia. We may prioritize protein restriction in CKD patients with a high risk of end-stage kidney disease (ESKD), classified to stage G4 to G5, but may loosen protein restriction in ESKD-low risk CKD stage G3 patients with proteinuria <0.5 g/day, and rate of eGFR decline <3.0 mL/min/1.73 m²/year. However, the effect of increasing protein intake alone without exercise therapy may be limited in CKD patients with sarcopenia. The combination of exercise therapy and increased protein intake is effective in improving muscle mass and strength in CKD patients with sarcopenia. In the case of loosening protein restriction, it is safe to avoid protein intake of more than 1.5 g/kgBW/day. In CKD patients with high risk in ESKD, 0.8 g/kgBW/day may be a critical point of protein intake.     

Utility of Geriatric Nutritional Risk Index in Patients with Chronic Kidney Disease: A Mini-Review

Chronic kidney disease (CKD) is one of the most significant risk factors for cardiovasculardisese. Malnutrition has been recognized as a significant risk factor for cardiovascular disease in patients with CKD, including those on chronic dialysis. Current studies showed higher all-cause and cardiovascular mortality rates in patients with CKD and malnutrition. Geriatric nutritional risk index (GNRI), a simple and validated nutritional screening measure for both elderly people and patients on dialysis, is based only on three objective parameters: body weight, height, and serum albumin level. Recently, we demonstrated that the cutoff GNRI for predicting all-cause and cardiovascular mortality was 96 in patients on hemodialysis. Moreover, together with left ventricular hypertrophy and low estimated glomerular filtration rate, the utility of GNRI as a significant determinant of cardiovascular events was demonstrated in non-dialysis-dependent patients with CKD. In the present review, we summarize available evidence regarding the relationship of GNRI with all-cause and cardiovascular mortality in patients with CKD including those on dialysis.     

Rehabilitation Nutrition in Patients with Chronic Kidney Disease and Cachexia

Rehabilitation nutrition is a proposed intervention strategy to improve nutritional status and physical function. However, rehabilitation nutrition in patients with cachexia and protein-energy wasting (PEW), which are the main nutrition-related problems in patients with chronic kidney disease (CKD), has not been fully clarified. Therefore, this review aimed to summarize the current evidence and interventions related to rehabilitation nutrition for cachexia and PEW in patients with CKD. CKD is a serious condition worldwide, with a significant impact on patient prognosis. In addition, CKD is easily complicated by nutrition-related problems such as cachexia and PEW owing to disease background- and treatment-related factors, which can further worsen the prognosis. Although nutritional management and exercise therapy are reportedly effective for cachexia and PEW, the effectiveness of combined nutrition and exercise interventions is less clear. In the future, rehabilitation nutrition addressing the nutritional problems associated with CKD will become more widespread as more scientific evidence accumulates. In clinical practice, early intervention in patients with CKD involving both nutrition and exercise after appropriate assessment may be necessary to improve patient outcomes.     

Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.     

Prevalence of Sarcopenia and Its Impact on Postoperative Outcome in Patients With Crohn's Disease Undergoing Bowel Resection

Background: Sarcopenia has been proposed to be a prognostic factor of outcomes for various diseases but has not been applied to Crohn's disease (CD). We aimed to assess the impact of sarcopenia on postoperative outcomes after bowel resection in patients with CD. Materials and Methods: Abdominal computed tomography images within 30 days before bowel resection in 114 patients with CD between May 2011 and March 2014 were assessed for sarcopenia as well as visceral fat areas and subcutaneous fat areas. The impact of sarcopenia on postoperative outcomes was evaluated using univariate and multivariate analyses. Results: Of 114 patients, 70 (61.4%) had sarcopenia. Patients with sarcopenia had a lower body mass index, lower preoperative levels of serum albumin, and more major complications (15.7% vs 2.3%, P = .027) compared with patients without sarcopenia. Moreover, predictors of major postoperative complications were sarcopenia (odds ratio [OR], 9.24; P = .04) and a decreased skeletal muscle index (1.11; P = .023). Preoperative enteral nutrition (OR, 0.13; P = .004) and preoperative serum albumin level >35 g/L (0.19; P = .017) were protective factors in multivariate analyses. Conclusion: The prevalence of sarcopenia is high in patients with CD requiring bowel resection. It significantly increases the risk of major postoperative complications and has clinical implications with respect to nutrition management before surgery for CD.