Evaluation of quadriceps muscle cross-sectional area using an ultrasonic diagnostic equipment with a wide field of view.

Skeletal muscle index measurement via dual-energy X-ray absorptiometry or bioelectrical impedance analysis is used to evaluate muscle mass when diagnosing sarcopenia. However, inherent challenges exist with these methods. We previously focused on muscle mass evaluation in the quadriceps femoris by using computed tomography (CT). In this observational study, we utilized a new ultrasound device with a wide field of view that can obtain CT-like images and investigated its usefulness. Reproducibility was investigated by calculating the intra- and inter-examiner intraclass correlation coefficient (ICC) by using three examiners and performing five measurements in 12 participants. In 123 participants (48 men, 75 women, mean age 78.2 ± 8.1 years), we investigated the correlation between the quadriceps cross-sectional area measured with supine ultrasound and CT images as well as between supine and sitting ultrasound images. Unadjusted, age-adjusted, and age-sex-adjusted correlations were calculated. Reproducibility was excellent (intra-examiner ICC[1,1]: 0.978, 0.987, and 0.994; inter-examiner ICC[2,1]: 0.993). The unadjusted, age-adjusted, and age-sex-adjusted correlations between the quadriceps cross-sectional area measured using supine ultrasound and CT were 0.949, 0.940, and 0.894, respectively. For sitting ultrasound, the corresponding values were 0.958, 0.953, and 0.912, respectively. Correlations between the supine and sitting ultrasound measurements were also good, with corresponding values of 0.952, 0.945, and 0.904, respectively. The tested ultrasound device showed excellent measurement reproducibility and had good correlations with CT images. Further studies with an increased numbers of clinical cases and additional evaluations should allow the device to become a screening tool for diagnosing sarcopenia.

Serum High-Density Lipoprotein Cholesterol Levels and the Risk of Kidney Function Decline: The Japan Specific Health Checkups (J­SHC) Study.

AIMS: Both low and high serum levels of high-density lipoprotein cholesterol (HDL-C) were reported to be associated with adverse kidney outcomes. However, this association has not been well investigated in the general Japanese population. METHODS: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008-2014. The association between serum HDL-C levels and 40% decline in estimated glomerular filtration rate (eGFR) was analyzed using Cox regression analysis. Trajectories of eGFR were compared using mixed-effects model. RESULTS: Among 768,495 participants, 6,249 developed 40% decline in eGFR during the median follow-up period of 34.6 (interquartile range: 14.8-48.4) months. Using serum HDL-C levels of 40-59 mg/dL as a reference, the adjusted hazard ratios (95% confidence intervals) for the kidney outcome of serum HDL-C levels of ＜40, 60-79 and ≥ 80 mg/dL were 1.26 (1.14-1.39), 0.91 (0.86-0.96), and 0.86 (0.78-0.93), respectively. Restricted cubic spline analysis showed that HDL-C levels of less than approximately 60 mg/dL were associated with an increased risk of kidney outcomes. Subgroup analysis showed that baseline eGFR and proteinuria modified the effects of serum HDL-C levels on kidney outcomes. The mixed-effects model showed that the lower category of HDL-C level was associated with a higher eGFR decline rate (p for interaction ＜0.001). CONCLUSIONS: Low HDL-C levels were associated with kidney function decline; however, high HDL-C levels were not associated with adverse kidney outcomes in the general Japanese population.

Unveiling the Patterns of Water Diuresis in Profound Hyponatremia Management in Intensive Care Unit Settings.

BACKGROUND: Hyponatremia treatment guidelines recommend avoiding excessive increases in serum sodium concentration (s[Na]) to prevent osmotic demyelination syndrome. Although an unexpected rise in s[Na] has been attributed to water diuresis during the treatment of hyponatremia, clinical courses of water diuresis are unclear. We conducted this study to investigate the clinical characteristics of water diuresis during profound hyponatremia management. METHODS: In this retrospective observational study, we examined patients with profound hyponatremia (s[Na] ≤120 mEq/L) admitted to the intensive care unit of a Japanese hospital. The manifestation of water diuresis was defined as a urine volume ≥2 ml/kg/h and a urinary sodium plus potassium concentration (u[Na+K]) ≤50 mEq/L. We analyzed changes in urine volume and u[Na+K] over time for patients experiencing water diuresis. This analysis employed a mixed-effects model with spline terms for time, and the results are graphically presented. RESULTS: Among 47 eligible patients, 30 (64%) met the criteria for water diuresis. The etiologies of hyponatremia were drug-related hyponatremia (n=10; 33%), primary polydipsia (n=8; 27%), hypovolemic hyponatremia (n=7; 23%), syndrome of inappropriate secretion of antidiuresis (n=7; 23%), and acute heart failure (n=1; 3%). Among patients with water diuresis, 27 (90%) experienced the manifestation of water diuresis within 24 hours after the start of correction. The increased urine volume and decreased u[Na+K] levels began several hours before the peak manifestation of water diuresis. Within 6 hours after the manifestation of water diuresis, 29 patients (97%) received electrolyte-free infusions and 14 (47%) received desmopressin. One patient (3%) with water diuresis experienced overcorrection. CONCLUSIONS: Water diuresis is common during the treatment for profound hyponatremia and typically occurs within the first 24 hours, preceded by changes in urinary characteristics. Early detection and prompt response to water diuresis through urine monitoring during the early periods of hyponatremia treatment may be effective for managing water diuresis.

Effective method for life-style modifications focused on dietary sodium intake in chronic kidney disease: sub-analysis of the FROM-J study.

BACKGROUND: Lifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice. METHODS: This study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects. RESULTS: Subjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012-1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019-1.318), CKD stage progression (OR 1.658, 95%CI: 1.177-2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073-3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013). CONCLUSION: An increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective. TRIAL REGISTRATION: The FROM-J study was registered in UMIN000001159 on 16/05/2008.

Comparison of gait analysis before and after unilateral total knee arthroplasty for knee osteoarthritis.

BACKGROUND: Gait ability can be objectively assessed using gait analysis. Three-dimensional gait analysis, the most commonly used analytical method, has limitations, such as a prolonged examination, high system costs, and inconsistently reported gait symmetry in patients with knee osteoarthritis (OA). Therefore, we aimed to evaluate the gait symmetry and changes before and after unilateral total knee arthroplasty (TKA) using the Walkway analyzer, a sheet-type gait analyzer. METHODS: The healthy group included 38 participants from the Locomotor Frailty and Sarcopenia Registry study with lower limb pain or Kellgren-Lawrence classification grade 3 or 4 OA. The OA group included 34 participants from the registry study who underwent unilateral TKA. The walking speed, step length, step width, cadence, stride time, stance time, swing phase time, double-limb support phase time, stride, step length, and step width were analyzed per side using the Walkway gait analyzer. RESULTS: No significant differences between the right and left sides were observed in the healthy group. In the OA group, the time indices and stance phase (p = 0.011) and the double-limb support phase time (p = 0.039) were longer on the contralateral side and the swing phase was longer on the affected side (p = 0.004) pre-operatively. However, these differences disappeared post-operatively. There were no significant differences in the spatial indices. Thus, this study revealed that patients undergoing unilateral TKA had an asymmetric gait pre-operatively, with a time index compensating for the painful side, and an improved symmetric gait post-operatively. CONCLUSIONS: The Walkway analyzer employs a simple test that requires only walking; hence, it is expected to be used for objective evaluation in actual clinical practice.

Liquid-Crystalline Photonic Sandwich: Electroresponsive Colloids of Clay Nanosheets Loading Photofunctional Dyes.

Colloidal clay nanosheets obtained by the delamination of layered crystals of smectite-type clay minerals in water form liquid crystals because of their shape anisotropy. Loading of organic dyes onto the liquid crystalline clay nanosheets will enable novel photonic materials, where photofunctions of the loaded dye are controlled by the liquid crystallinity of the clay nanosheets. However, adsorption of organic dyes onto the nanosheets renders the nanosheet surfaces hydrophobic, and consequently, colloidal stability of the nanosheets is lost. In this study, this drawback is overcome by sandwiching cationic stilbazolium dyes between a pair of synthetic fluorohectorite nanosheets. This is realized by the preparation of stilbazolium-clay second-stage intercalation compounds characterized by intercalation of dye cations into every other interlayer space of the hectorite clay, where nonintercalated interlayer spaces are occupied by Na+ ions. The second-stage intercalation compounds are obtained by partial ion exchange of mother clay mineral incorporating Na+ ions in all of the interlayer spaces and delaminated from the Na+-containing interlayer spaces to form clay nanosheets sandwiching the dye molecules. Aqueous colloids of the dye-sandwiching clay nanosheets form colloidal liquid crystals, and the dye-sandwiching liquid crystalline clay nanosheets respond to an applied AC electric field to be aligned parallel to the electric field. The assembled structure of the dye-sandwiching clay nanosheets under the electric field is characterized by aligned discrete clay platelets, which is somewhat different from that of a colloidal liquid crystal of clay nanosheets without dye loading characterized by macroscopic liquid crystalline domains up to submillimeters. The electric alignment of the clay nanosheets induces alteration of light absorption of the sandwiched stilbazolium molecules, which verifies a strategy of constructing stimuli-responsive photonic materials of clay-organic hybrids.

Targeted vibratory therapy as a treatment for proprioceptive dysfunction: Clinical trial in older patients with chronic low back pain.

INTRODUCTION: Proprioceptive function declines with age, leading to falls, pain, and difficulties in performing activities of daily living among older adults. Although individuals with low back pain (LBP) exhibit decreased lumbosacral proprioception in various postures, the mechanism by which reduced proprioceptive function causes LBP remains uncertain. Vibratory stimulation may enhance proprioceptive function; however, its efficacy in treating LBP has not been investigated. Thus, we investigated the feasibility of improving proprioceptive function and its effect on alleviating chronic LBP in older patients through targeted vibratory therapy (TVT) administration. METHODS: This single arm designed trial included older patients aged >65 years with non-specific chronic LBP. TVT involved applying vibratory stimulation, matching the frequency of dysfunctional receptors, for 1 min daily over 14 days to activate proprioceptors; patients performed TVT three times daily at home. In cases of reduced proprioceptive function at multiple sites, TVT was aimed at the lowest frequency band value. LBP and proprioceptive function were evaluated at 2 weeks after TVT and at 2 weeks after the end of TVT in patients with declined proprioception in the trunk or lower extremities. RESULTS: Overall, 56 patients with chronic LBP were enrolled; 32 patients were recruited for treatment based on a proprioceptive dysfunction diagnosis and 24 patients were recruited with a normal diagnosis with no significant differences observed between the two sets of patients in sarcopenia-related factors and clinical proprioception-related characteristics. No patient had any adverse events. Two weeks after TVT, the numerical pain rating scale score improved to <3 points in 78.1% of patients, with 73.1% of patients achieving a score of ≤ 3 points. Proprioceptive function improved in 81.3% of cases, and engagement in activities of daily living improved significantly. CONCLUSIONS: TVT demonstrated efficacy in improving proprioception and alleviating LBP in older patients with impaired proprioceptive function without affecting non-targeted proprioceptors.

Elevated resting heart rate is associated with mortality in patients with chronic kidney disease.

A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated. A total of 1353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate < 70/min, ≥ 70 and < 80/min, ≥ 80 and < 90/min, and ≥ 90/min). During the median observation period of 4.9 years, 123 participants died, and 163 cardiovascular events occurred. Compared with the reference level heart rate < 70/min group, the adjusted hazard ratios (HRs) for all-cause mortality were 1.74 (1.05-2.89) and 2.61 (1.59-4.29) for the heart rate ≥ 80 and < 90/min group and heart rate ≥ 90/min group, respectively. A significantly higher risk of cardiovascular events was observed in the heart rate ≥ 80/min and < 90/min group (adjusted HR 1.70, 1.10-2.62), but not in the heart rate ≥ 90/min group (adjusted HR 1.45, 0.90-2.34). In patients with non-dialysis-dependent CKD, a higher resting heart rate was associated with increased all-cause mortality.

Pulse pressure modifies the association between diastolic blood pressure and decrease in kidney function: the Japan Specific Health Checkups Study.

Background: Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP. Methods: This longitudinal study used data from the Japan Specific Health Checkups Study was conducted between 2008 and 2014. The participants were stratified into three PP subgroups (low PP ≤39, normal PP 40-59 and high PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model. Results: Among 725 022 participants, 20 414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low- and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in the high-PP subgroup, with a U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61-80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15-1.38) and 1.86 (1.62-2.14), respectively. Conclusions: In this large population-based cohort, DBP was differently associated with kidney outcome by PP level; lower DBP was significantly associated with a higher incidence of kidney outcome in the high-PP subgroup but not in the low- and normal-PP subgroups.

Early surgery within 48 hours of admission for hip fracture did not improve 1-year mortality in Japan: a single-institution cohort study.

INTRODUCTION: Early surgery for hip fracture, within 48 hours of hospital admission, is effective in reducing mortality. However, the average preoperative waiting time for hip fractures in Japan is 4.5 days and the 1-year mortality rate after a hip fracture is 10% in Japan. This study aimed to investigate whether early surgery, within 48 hours, could reduce the 1-year mortality rate in patients with hip fractures in Japan. METHODS: This cohort study involved 402 consecutive patients with hip fractures who underwent surgical treatment between January 2013 and September 2019. The exclusion criteria were an age of <60 years and in-hospital injury. A total of 389 patients were included in this study. The patients were divided into two groups: those who underwent early surgery within 48 hours of admission (early group) and those who di not undergo early surgery (delayed group). We compared patient characteristics and treatment outcomes between the 2 groups. RESULTS: A comparison of patient characteristics revealed that the early group had lower hemoglobin levels (P=0.046), lower C-reactive protein levels (P = 0.031), lower numbers of patients with weekend hospitalization, lower numbers of patients with a history of using medications that may cause bleeding (P < 0.01), and who received general anaesthesia (P < 0.01). However, there were no significant differences with regard to the other variables between the 2 groups. A treatment outcome analysis showed that the early group had shorter waiting times for surgery (P < 0.01) and shorter stays in acute-care wards (P < 0.01). However there were no differences in the total hospital stay, Barthel index at discharge, home discharge rates, in-hospital mortality rates, and 1-year mortality. CONCLUSION: Our findings indicate that early surgery did not reduce the 1-year mortality rate in older patients with hip fractures in Japan.

Geriatric Nutritional Risk Index is associated with adverse outcomes in patients with hypertension: the Fukushima Cohort study.

Malnutrition is reportedly associated with adverse clinical outcomes in various populations. However, associations between nutritional status and adverse outcomes in patients with hypertension have not been sufficiently elucidated. We therefore aimed to investigate the impact of nutritional status as evaluated by the Geriatric Nutritional Risk Index (GNRI) on adverse outcomes in patients with hypertension. We conducted a retrospective cohort study of 1588 hypertensive patients enrolled in the Fukushima Cohort Study. Participants were categorized into tertiles (T1-T3) according to GNRI at baseline. The primary endpoint of the present study was a kidney event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease requiring kidney replacement therapy. Associations between GNRI and kidney events were assessed using Kaplan-Meier curves and multivariate Cox regression analyses. Median age was 64 years, 55% were men, median eGFR was 63.1 mL/min/1.73 m2, and median GNRI was 101.3. The lower GNRI group (T1) showed an increased incidence of kidney events in the Kaplan-Meier curve analysis. Compared to the highest GNRI group (T3), lower GNRI carried a higher risk of kidney events for both T2 (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.71-2.68) and T1 (HR 3.59, 95%CI 1.96-6.63). Similar relationships were observed for risks of all-cause death and cardiovascular events. Lower GNRI was associated with kidney events, all-cause death, and cardiovascular events in patients with hypertension. Nutritional status as evaluated by GNRI could offer a simple and useful predictor of adverse outcomes in this population.

Cigarette smoking and progression of kidney dysfunction: a longitudinal cohort study.

INTRODUCTION: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established. METHOD: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis. RESULTS: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001). CONCLUSION: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria.

Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle.

BACKGROUND: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. METHODS: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. RESULTS: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. CONCLUSIONS: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Predicting CKD progression using time-series clustering and light gradient boosting machines.

Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2. Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m2; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m2; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m2; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m2; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m2). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m2.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study.

OBJECTIVE: The Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease and CVD. This study aimed to measure health-related quality of life in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured quality of life (QOL) scores. METHODS: The EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the Frontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in Japan study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. RESULTS: The response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880-0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.826-1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767-0.881), and the median was 0.828 (IQR, 0.755-1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811-0.943), and the median was 1.000 (IQR, 0.723-1.000). The mean QOL score in participants with 50% decline in estimated glomerular filtration was 0.893 (95% CI, 0.860-0.926), and the median was 0.889 (IQR, 0.825-1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere-Terpstra test for trend (P = .002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. CONCLUSION: We suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of end-stage kidney disease/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future health-related quality of life in patients with CKD.

Renal Immune-related Adverse Event of Pembrolizumab Masked by Pemetrexed.

A Japanese woman in her 60s developed a kidney injury 9 weeks after treatment with pemetrexed, carboplatin, and pembrolizumab for stage IV lung adenocarcinoma. A renal biopsy showed chronic tubulointerstitial damage with minimal focal interstitial inflammation, consistent with pemetrexed-induced nephropathy; thus, pemetrexed was withdrawn. However, the kidney injury continued to worsen. A repeated biopsy showed severe acute tubulointerstitial nephritis, suggestive of a pembrolizumab-induced immune-related adverse event (irAE). The worsening after pemetrexed discontinuation suggested that the irAE had already begun, as the first biopsy showed focal inflammation. This case suggests thatcombining immune checkpoints and chemotherapy requires considering concurrent drug-induced nephrotoxicity.

Relationship between quadriceps muscle computed tomography measurement and motor function, muscle mass, and sarcopenia diagnosis.

Background: The quadriceps muscle is one of the human body's largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation. Methods: A total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance. Results: In men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p<0.05), excluding only balance ability. BMI-corrected CSA was significantly correlated with all eight motor functions in men and women (p<0.05). In the diagnosis of sarcopenia based on skeletal muscle index, CSA (area under the curve (AUC) 0.935) and CSA×CTV (AUC 0.936) and their correction by height (CSA/height (AUC 0.917) and CSA×CTV/height (AUC 0.920)) were highly accurate and useful for diagnosis in men but moderately accurate in women (CSA (AUC 0.809), CSA×CTV (AUC 0.824), CSA/height (AUC 0.799), CSA×CTV/height (AUC 0.814)). Conclusion: The present results showed that a single CT image of the quadriceps muscle at the mid-thigh is useful for diagnosing sarcopenic changes, such as loss of muscle mass, muscle weakness, and muscle function.

Machine learning versus binomial logistic regression analysis for fall risk based on SPPB scores in older adult outpatients.

Objective: To compare the performance of the diagnostic model for fall risk based on the short physical performance battery (SPPB) developed using commercial machine learning software (MLS) and binomial logistic regression analysis (BLRA). Methods: We enrolled 797 out of 850 outpatients who visited the clinic between March 2016 and November 2021. Patients were categorized into the development (n = 642) and validation (n = 155) datasets. Age, sex, number of comorbidities, number of medications, body mass index (BMI), calf circumference (left-right average), handgrip strength (left-right average), total SPPB score, and history of falls were determined. We defined fall risk by an SPPB score of ≤6 in men and ≤9 in women. The main metrics used for evaluating the machine learning model and BLRA were the area under the curve (AUC), accuracy, precision, recall (sensitivity), specificity, and F-measure. The commercial MLS automatically calculates the parameter range of the highest contribution. Results: The participants included 797 outpatients (mean age, 76.3 years; interquartile range, 73.0-81.0; 288 men). The metrics of the current diagnostic model in the commercial MLS were as follows: AUC = 0.78, accuracy = 0.74, precision = 0.46, recall (sensitivity) = 0.81, specificity = 0.71, F-measure = 0.59. The metrics of the current diagnostic model in the BLRA were as follows: AUC = 0.77, accuracy = 0.75, precision = 0.47, recall (sensitivity) = 0.67, specificity = 0.77, F-measure = 0.55. The risk factors for falls in older adult outpatients were handgrip strength, female sex, experience of falls, BMI, and calf circumference in the commercial MLS. Conclusions: The diagnostic model for fall risk based on SPPB scores constructed using commercial MLS is noninferior to BLRA.

Impact of red blood cell distribution width-albumin ratio on prognosis of patients with CKD.

The red blood cell distribution width-albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan-Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan-Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68-2.78 and 2.92, 95% CI 1.44-5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.

Weight Loss Improves Liver Dysfunction and Dipstick Proteinuria in Obesity: The Japan Specific Health Checkups Study.

Introduction: Obesity and inappropriate lifestyle is the major risk factors for liver dysfunction and proteinuria. Nevertheless, previous studies have not described the differential impacts of body weight changes and lifestyle modification on already developed liver dysfunction and proteinuria. Methods: The original cohort was 933,490 individuals from the Japanese general population. In this investigation, we included 36,256 obese individuals with elevated levels of aspartate aminotransferase and/or alanine aminotransferase (≥31 IU/L) or positive proteinuria (+/- or more) in both the first and second years. Outcomes were the first normalization of these data defined as improvement in liver dysfunction and proteinuria. Times to outcomes were assessed using the Cox proportional hazards modeling for -1 kg/m2/year change in body mass index (BMI) changes in exercise and alcohol intake. Results: The multivariable-adjusted hazard ratio (HR) for incident improvement in liver dysfunction with BMI change -1.0 kg/m2/year was 1.07 (95% confidence interval [CI] 1.05-1.09) in obesity and that with improved proteinuria was 1.04 (95%CI 1.02-1.07). Compared to subjects without exercise habits, subjects who gained exercise habits exhibited a higher rate of improvement in liver dysfunction (HR 1.08; 95%CI 1.01-1.15) but not in proteinuria (HR 0.98; 95%CI 0.88-1.08). Compared to subjects with continuous alcohol intake habits, subjects who quit alcohol intake also showed a higher rate of improvement in liver dysfunction (HR 1.20; 95%CI 1.09-1.32). Conclusions: This study suggested that weight loss greater than 1 kg/m2/year improves liver dysfunction and dipstick proteinuria in obesity. Particularly, liver dysfunction can be remedied by acquiring an exercise habit and quitting alcohol intake.