Background Fluid retention and the obesity paradox often mask true muscle wasting in patients with proteinuric chronic kidney disease (CKD), and conventional quantity-based metrics such as body mass index or cross-sectional tissue area fail to capture this. We asked whether tissue radiodensity, a quality-based measure, is more sensitive to proteinuric injury than volumetric indices, and examined the role of “0 HU drift”—the convergence of tissue attenuation toward water density—as an early signal of metabolic remodeling. Methods We retrospectively analyzed 1,416 CKD patients grouped by urinary albumin-to-creatinine ratio (KDIGO stages A1–A3). A custom 2D U-Net segmented muscle and adipose compartments on non-contrast CT at the T12 level. Monotonic trends across stages were tested with the Jonckheere–Terpstra test. We built a three-step hierarchical linear regression model to link visceral fat mean attenuation (VF-HU) to proteinuria severity, adjusting stepwise for demographics, BMI, comorbidities, eGFR, and serum albumin. Binary logistic regression tested VF-HU as a predictor of sarcopenia tendency. Results Quality metrics clearly outperformed quantity metrics in tracking proteinuria severity. Subcutaneous fat area did not change across KDIGO stages (P = 0.541), yet its mean attenuation rose significantly toward 0 HU (Z = 4.738, P < 0.001), a pattern consistent with progressive fluid infiltration. VF-HU climbed (visceral fat “whitening”) and skeletal muscle density fell (myosteatosis) as proteinuria worsened. After adjusting for serum albumin, eGFR, and comorbidities, VF-HU remained linked to proteinuria severity (standardized β = 0.16, P = 0.015), which argues against a pure edema artifact and points to genuine adipose remodeling. In the logistic model, each 1-HU rise in VF-HU raised the odds of sarcopenia tendency by 11.6% (OR 1.116, 95% CI 1.097–1.135, P = 0.002); eGFR did not reach significance (P = 0.418). Conclusions At the T12 level, radiodensity metrics discriminated proteinuria stages better than volumetric indices. VF-HU was independently tied to both disease severity and low muscle quality, making it a candidate marker for metabolic risk stratification. Because routine chest CT already captures T12, AI-based opportunistic screening of tissue quality is feasible in clinical practice. Longitudinal work is now needed to test whether qualitative changes truly precede volumetric loss and to confirm their prognostic value.
Purpose We examined whether chest CT-derived visceral adipose tissue attenuation (VAT_Hu), an imaging marker of adipose tissue quality, was associated with anemia and hypoalbuminemia in adults with non-dialysis chronic kidney disease (CKD) stages 1–4. Methods In this retrospective cross-sectional study, 2,817 adults with CKD stages 1–4 who underwent chest CT and had available clinical and laboratory data were included. VAT_Hu was analyzed per standard deviation (SD) increase and by quartiles. The primary outcomes were anemia and hypoalbuminemia. Multivariable logistic and linear regression models adjusted for age, sex, body mass index, systolic blood pressure, smoking, alcohol use, diabetes, hypertension, estimated glomerular filtration rate, albuminuria, and albuminuria source. Results VAT_Hu was available in 2,803 participants. Mean age was 64.4 ± 10.8 years, 63.4% were men, 30.5% had anemia, and 10.7% had hypoalbuminemia. Each 1-SD increase in VAT_Hu was associated with higher odds of anemia (OR 1.47, 95% CI 1.33–1.62) and hypoalbuminemia (OR 1.60, 95% CI 1.39–1.84). Compared with the lowest quartile, the highest quartile was associated with higher odds of anemia (OR 2.26, 95% CI 1.71–2.98) and hypoalbuminemia (OR 2.80, 95% CI 1.80–4.36). Higher VAT_Hu was also associated with lower hemoglobin and serum albumin independent of visceral adipose tissue area. Conclusion Higher chest CT-derived VAT attenuation was independently associated with anemia and hypoalbuminemia in non-dialysis CKD stages 1–4, suggesting that CT-derived adipose tissue quality may provide information beyond adipose quantity alone.
Background & Aims The purpose of this study was to assess the association between N-terminal prohormone of type B natriuretic peptide (NT-proBNP) and long-term mortality in hospitalized oldest-old adults and to explore the mediating role of malnutrition and muscle loss. Methods This prospective cohort study was conducted among 360 hospitalized patients ≥ 80 years of age (median age 87 [IQR 84–90] years, 24.4% women) in the Department of Geriatrics. The Geriatric Nutritional Risk Index (GNRI) and Mini Nutritional Assessment Short Form (MNA-SF) were used for nutritional assessment, while calf circumference was used as a measure of muscle mass. A Cox proportional hazard model was used to assess the relationship between NT-proBNP levels and mortality. Mediation analysis was used to explore the mediating effects of malnutrition and muscle loss. Results The median follow-up was 4.1 years with 159 (44.1%) deaths. Mortality risk increased by 32% per 2-fold increase in NT-proBNP levels (full adjusted hazard ratio: 1.32 [95% CI, 1.20–1.46]). A mediation analysis showed that a lower GNRI score and decreased calf circumference mediated the effects of high NT-proBNP and mortality risk, with an estimated relative effect size of 28.9%, while MNA-SF and calf circumference mediated the effect, with an estimated relative effect size of 25.3%. Conclusions NT-proBNP levels were associated with long-term mortality in hospitalized older patients. Moreover, the detrimental effects of NT-proBNP on survival were partly mediated by malnutrition and muscle loss.
BACKGROUND:Inflammation and oxidative stress are important pathological processes of contrast-induced acute renal injury (CIAKI). This study explored whether DMF had therapeutic effects and investigated the underlying mechanism in CIAKI. METHODS:A CIAKI animal model was established in C57BL/6J mice with iohexol, and DMF was used as an intervention. In vitro, HK-2 cells were treated with iohexol and DMF. RNA-seq analysis was performed on the renal tissue of the mice. Protein-protein interaction (PPI), and enrichment analysis were subsequently conducted. In addition, endoplasmic reticulum stress (ERS) activation and STAT3 inhibition were used to study the relationships among ERS, the JAK2-STAT3 pathway and pyroptosis. RESULTS:DMF improved the renal function of CIAKI model mice. Enrichment analysis revealed that the differentially expressed genes (DEGs) were enriched mostly in the acute phase response and the JAK-STAT pathway. The results revealed that inflammation, ERS and pyroptosis increased in the CIAKI group but decreased after DMF treatment. Further study revealed that the JAK2-STAT3 pathway was overactivated in vivo and in vitro and that DMF inhibited the JAK2-STAT3 pathway. In addition, ERS activation could increase the JAK2-STAT3 pathway and pyroptosis, while STAT3 knockdown could reverse pyroptosis, indicating that ERS could activate the JAK2-STAT3 pathway, further triggering pyroptosis. DMF ameliorated pyroptosis through regulating ERS and the JAK2-STAT3 pathway in CIAKI. CONCLUSION:This study demonstrated that DMF had renoprotective effects on CIAKI. DMF ameliorated pyroptosis through the inhibition of ERS and the JAK2-STAT3 pathway.
Abnormal Wnt5a expression, mitochondrial abnormalities and calcium overload have been detected in many metabolic diseases. However, the association of Wnt5a-Ca2+ and mitochondrial dysfunction in diabetic nephropathy (DN) progression remains unknown. We used streptozotocin-induced DBA2/J male mice as a DN model. The mice were treated with losartan (10 mg/kg/d*12 w) or losartan (10 mg/kg/d*12 w) + levamlodipine (5 mg/kg/d*12 w). High glucose (HG) (40 mmol/L)-induced HK-2 cells were used for in vitro experiments. Wnt5a and mitochondrial calcium uniporter (MCU) expression, mitochondrial dynamics, morphological changes and Ca2+ concentration were detected in different groups. Levamlodipine, a kind of calcium channel blocker, in combination with losartan ameliorated tubular injury and reversed mitochondrial fragmentation and dynamic dysfunction more efficiently than losartan alone in diabetic mice. Wnt5a induced Ca2+ uptake and aggravated mitochondrial fusion-fission disorder in HG-stimulated HK-2 cells. In addition, increased MCU formation was found in the mitochondria of tubular cells under HG stimulation and was upregulated by the activation of the Wnt5a-Ca2+ pathway. Our study showed that the Wnt5a-Ca2+ signalling pathway was involved in Ca2+ overload-induced mitochondrial dysfunction possibly through MCU in tubular injury and DN progression. A calcium channel blocker in combination with a renin-angiotensin system inhibitor (RASi) could be a promising therapeutic strategy in DN patients.
Exercise benefits patients on maintenance hemodialysis (MHD) by addressing complications and dysfunctions. Elastic band exercise is cost-effective, but its safety, efficacy, and feasibility during dialysis are not well-established. The aim of this study is to investigate the physical and mental effects of intradialytic elastic band exercise in patients on MHD. Sixty patients on MHD were randomly assigned to the exercise or control group (30 patients/group). The control group received routine hemodialysis care, whereas those in the exercise group performed intradialytic elastic band exercises for 0.5-2 h during hemodialysis three times a week for 12 weeks. Physical function (Short Physical Performance Battery [SPPB]), cognitive function (Montreal Cognitive Assessment [MoCA]), fatigue (14-item Fatigue Scale [FS-14]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), and anxiety and depression (Hamilton Anxiety Rating Scale [HAMA]/Hamilton Depression Rating Scale [HAMD]) were assessed. The exercise group showed significant improvements in SPPB (p = 0.008) and MoCA (p < 0.001) scores compared to pre-intervention and control groups. FS-14 scores decreased significantly (p = 0.005). PSQI (p < 0.001) and HAMA (p < 0.001) scores improved post-intervention but not versus control. HAMD scores reduced significantly (p < 0.001). Satisfaction and recommendation scores were 9.57 and 9.71. In conclusions, intradialytic elastic band exercise improved physical and cognitive function and alleviated fatigue, sleep issues, depression, and anxiety in patients on MHD. With high compliance, no significant adverse events, and high patient satisfaction, it is recommended as a routine intervention during dialysis.
Genetic mutations are closely linked to various renal diseases, revealing important molecular mechanisms that contribute to kidney dysfunction. Here, we reported a 35-year-old Chinese female diagnosed of glomerulotubular nephropathy with multiple extra-renal manifestations including ptosis, corneal dystrophy, macular degeneration, right foot syndactyly. Whole-exome sequencing identified a homozygous frameshift variant in FAT1 (NM_005245: c.7444_7445delGT, p.Val2482AsnfsTer16). Further analysis revealed that this mutation caused translation repression of FAT1. RNA sequencing showed dysregulation of cell adhesion and Rap1 signaling pathways, while immunofluorescence staining demonstrated disrupted β-catenin junctions and cytoskeletal abnormalities in patient-derived primary urinary epithelial cells. Pull-down assays indicated that the reduction in activated Rap1 levels was correlated with the observed cellular defects. These findings provide compelling evidence that this loss-of-function homozygous FAT1 variant is causally associated with nephropathy and congenital anomalies, likely through degradation of transcribed mRNA and impaired protein expression. The results emphasize the critical role of FAT1 in renal development and provide new insights into the molecular mechanisms underlying these conditions.
A 50-year-old man presented to our hospital with bone pain for 2 years. One year before admission, he quit his job as a miner owing to exacerbating pain. Gradually, fatigue and weakness developed, and he became wheelchair dependent. He was diagnosed with lumbar disc herniation at local hospitals and received physical therapy, but pain persisted. He was previously healthy, took no medications, and had stopped smoking and drinking alcohol since disease onset; he denied hepatitis B infection and other chronic diseases.
Introduction Mitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied. Methods In this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI. Results Our results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP. Conclusion In summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.
In recent years, the effective management of patients with chronic kidney disease (CKD) is gaining growing attention. In 2014, our hospital established the CKD generalist-specialist combination management model, which incorporates a set of CKD management processes. The generalist component incorporates the following, general practitioners from 6 community health centers in the surrounding areas (with about 650 000 permanent residents in the region) joining hands, setting up a management team composed of doctors and nurses, and formulating management protocols for patient follow-up, patient record management, screening, risk assessment, examination and treatment, nutrition and exercise, and two-way referrals. The specialist component of the model incorporates the following, providing trainings for general practitioners in the in the community in the form of lectures on special topics and case discussion sessions, and organizing 7 national-level workshops for continuing medical education in the past decade, covering about 1 400 participants. In addition, regular meetings of the support groups of patients with renal diseases were organized to carry out information and education activities for patients. We have set up 4 community-based training centers and 6 specialized disease management centers, including one for diabetic nephropathy. We have retrospectively analyzed the risk factors of elderly CKD patients by establishing the elderly physical examination database (which has a current enrollment of 26 000 people), the elderly community CKD cross-sectional survey database, and the elderly CKD information management system. After 10 years of management practice, the level of institutionalization and standardization of CKD specialty management in our hospital has been improved. Moreover, we have expanded the management team and extended the management base from the hospital to community. We have improved the level of CKD management in community health centers and improved the specialty competence of the general practitioners in the communities. The generalist-specialist combination management model makes it possible for CKD patients to receive early screening and treatment, obtain effective and convenient follow-up and referral services, and improve their quality of life. Patients with complications such as diabetes, hypertension, and sarcopenia could access treatments with better precision. It is necessary to carry out the generalist-specialist integrated management of CKD, which is worthy of further development and improvement.
Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.
Objective: This study aimed to explore the effects of fluid hydration status on ultrasound muscle measurement in hemodialysis (HD) patients. Methods: Ultrasound muscle examination of the right rectus femoris and bioelectrical impedance analysis measurement of the right lower limb were performed in HD patients at the periods of predialysis and postdialysis. The correlations between the changes in the corresponding ultrasound and bioelectrical impedance analysis variables were analyzed. Results: A total of 50 patients on maintenance HD were included, with mean age of 52.6 +/- 13.5 years. Patients were 40% female (n=20), and average dialysis duration was 2.62 +/- 2.42 years. Compared to predialysis, the measurements of cross-sectional area, muscle thickness, echo intensity (EI), and their percentage changes all decreased significantly after the HD procedure (P<.05). The change in EI and its percentage change were significantly correlated with changes in total body water, intracellular water, and extracellular water (P<.05). Conclusions: The HD session may have significant effects on ultrasound muscle measurement. Both the indicators of muscle quantity (cross-sectional area and muscle thickness) and quality (EI) significantly decreased after HD, which may contribute to the change in fluid hydration status and the change in fluid composition.
糖尿病肾病(diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)最常见的并发症之一,目前临床上以药物治疗为主.口服降糖药物除可优化血糖控制、降低低血糖发生风险外,还可影响DN进展.其中,二肽基肽酶-4抑制剂(dipeptidyl peptidase-4 inhibitor,DPP-4i)是一种在肠促胰岛素系统水平变化中起作用的口服降糖药物.DPP-4i在体外模型中显示出额外的多效性作用,包括减少炎症、纤维化和氧化损伤等,进一步表明其具有潜在的肾脏保护作用.DPP-4i可能有助于延缓DN进展,但尚需进一步研究证明其对肾脏的特异性益处.现就DPP-4i的生物学功能、对DN的作用机制以及临床疗效等进行综述,以期为临床治疗提供新思路.
Background Disability in activities of daily living (ADL) significantly increases the risk of mortality among patients undergoing hemodialysis. Malnutrition and decreased exercise capacity are closely correlated with ADL disability. Phase angle (PhA) has been proposed as a measure of nutritional status and exercise capacity. This study aims to investigate the prevalence of ADL disability in hemodialysis patients and its association with PhA. Methods A prospective, observational study was conducted, involving hemodialysis patients treated between November 2019 and January 2020 in an affiliated hospital of Chinese university. ADL was measured using both basic ADL (BADL) scales and instrumental ADL (IADL) scales. PhA measurements were obtained using a BIA device while the patients were in the supine position after dialysis. Results A total of 237 hemodialysis patients with a mean age of 60.01 ± 13.55 years were included in this study. The prevalence of disability in ADL was 43.5%. Multivariable analysis results showed a robust association between low PhA and disability in both BADL and IADL (for each unit decrease in PhA: odds ratio 4.83 [95% CI: 2.56–9.0], and 3.57 [95% CI: 2.14–5.95], respectively). The optimal cut-off values of PhA for disability in BADL and IADL were 4.8 and 5.4, with the area under the ROC curve (AUC) were 0.783 (0.727, 0.835) and 0.799 (0.743, 0.848), respectively. Conclusions Low PhA is strongly associated with disability in ADL in hemodialysis patients. These findings suggest that PhA may serve as a potentially objective measure of ADL disability in hemodialysis patients.
肌少症是一组与年龄相关的疾病,表现为肌肉力量及运动能力减退.肌少症会造成跌倒和骨折风险增加,导致患者运动功能失调、生活质量下降,也是引发患者日常生活能力下降的重要原因[1].肌少症的发生涉及多种风险因素和机制[2,3] ,血液透析患者由于年龄及透析龄增长、运动量不足及营养不良等因素,致使肌少症、自主生活能力失能高发病率[4,5].透析患者丧失独立生活能力,需要别人长期照料,增加血透患者医疗支出费用和死亡风险[6,7].少数民族地区透析患者语言沟通相对困难,医疗费用承受能力差,器械设备较欠缺,依从性相对较差,患者及医护对肌少症和自主生活能力失能及其危害普遍缺乏认识.随着2019年亚洲肌少症指南更新,本研究调查少数民族地区透析患者肌少症患病率以及其危险因素,并评估IADL失能情况,为进一步防治提供前期基础以及依据.
脆性骨折危害性极大,发生后患者死亡率成倍升高.大多数死亡患者可能归因于共病或术后并发症,而并不是骨折本身,因此识别和量化风险因素,尤其是其对死亡率的影响,将有助于早期发现存在这些风险因素的患者,对其进行综合评估,从而实现优化手术和康复计划.脆性骨折死亡率预测因素有年龄、性别、生活状态、合并疾病、生化指标等.该文对脆性骨折死亡率预测因素研究进展进行综述.
Background Patients on hemodialysis often suffer from reduced muscle strength and exercise capacity due to the decreased quantity and quality of muscle. Cumulative studies showed ultrasound echo intensity (EI) had great potential in evaluating muscle quality. The objective of this study was to evaluate the relationship between EI of skeletal muscle and physical function of patients on maintenance hemodialysis. Methods Cross-sectional area (CSA) and mean EI of the right rectus femoris were measured by ultrasound to evaluate the quantity and quality of the muscle, respectively. Physical function was measured by handgrip strength (HGS), gait speed, sit-to-stand 60 s (STS-60) test, and instrumental activities of daily living (IADL) scale. Results A total of 107 patients on hemodialysis were included, with women accounting for 37.3% ( n = 40), and a mean age of 53.53 ± 12.52 years. Among the patients on hemodialysis, EI was moderately and negatively correlated with HGS ( r = − 0.467, P < 0.001), gait speed ( r = − 0.285, P = 0.003), and STS-60 ( r = − 0.313, P = 0.001). Multiple regression analyses adjusted for CSA showed that the enhanced EI of patients on hemodialysis remained associated with worse HGS (β = − 0.207, P = 0.047), lower gait speed (β = − 0.002, P = 0.001), less STS-60 (β = − 0.136, P = 0.049), and a higher likelihood of dependency in IADL (Odds Ratio: 1.070, 95% CI: [1.033–1.111], P = 0.001). Conclusions In patients on hemodialysis, enhanced EI in the skeletal muscle measured via ultrasound was correlated with poor physical performance. The combined muscle quality and muscle quantity evaluation provide more information for assessing the level of physical function of the patients.
Objective:To compare the consistency between bioelectrical impedance analysis(BIA)and dual-energy X-ray absorptiometry(DXA)in skeletal muscle mass assessment in elderly patients with advanced chronic kidney disease(CKD), and to provide a basis for accurate clinical diagnosis of sarcopenia.Methods:Elderly patients with advanced CKD at the Department of Nephrology of Shanghai Sixth People's Hospital were included.Parameters for physical performance included handgrip strength and gait speed, and body muscle mass was measured by DXA and multifrequency BIA.The consistency between the two methods was assessed by the intraclass correlation coefficient, Bland-Altman analysis and kappa coefficient test.Results:This study included 67 elderly patients with advanced CKD with a mean age of(70.7±6.1)years and an average BMI of(24.6±3.5)kg/m 2.The proportion of enrolled male patients was 61.2% and the mean estimated glomerular filtration rate was(27.7±12.7)ml·min -1·1.73m -2.The intraclass correlation coefficients of muscle mass and appendicular skeletal-muscle mass index(ASMI)measured by BIA and DXA ranged from 0.81 to 0.90.Bland-Altman analysis showed that BIA overestimated muscle mass against DXA, and the mean difference in ASMI was(0.44±0.13)kg/m 2.In addition, there was a moderate agreement between the two measurement methods for determining muscle loss(Kappa=0.47). Conclusions:BIA and DXA offer a fair level of consistency in the assessment of muscle mass in elderly patients with advanced CKD.However, compared with DXA, BIA overestimates muscle mass in elderly patients with CKD.