Loss of Lean Mass in Rheumatoid Arthritis Is Associated With Loss of Total and Visceral Fat

Journal of Cachexia Sarcopenia and Muscle · 2026-02-01

ABSTRACT Purpose Rheumatoid cachexia has been described as a process of concurrent muscle loss and gain of adipose tissue. We evaluated longitudinal changes in body composition in patients with rheumatoid arthritis (RA) to evaluate the changes in adiposity that accompany loss of lean mass. Methods We combined and assessed three independent longitudinal RA cohorts that included assessments of body composition. Whole body DXA was performed in all participants to quantify appendicular lean mass index (ALMI, kg/m 2 ) and fat mass index (FMI, kg/m 2 ). Independent associations between loss of ALMI during follow‐up and FMI over the same time‐period were assessed adjusting for age, sex, race, baseline body composition and study using mixed‐effects regression to account for clustering by study. Changes in adipokines (adiponectin and leptin) were also assessed over time in similar models. Visceral fat area was determined from DXA (cm 2 ) in one of the cohorts and was also assessed. Results Among 451 patients with a mean (SD) age of 58.3 (10.5), the mean (SD) ALMI was 6.97 (1.41) kg/m 2 . Longitudinal analyses were conducted in 361 participants with follow‐up data [average follow‐up 2.65 (0.71) years]. Of these, 195 lost lean mass (experienced a negative change in ALMI during follow‐up), while 166 gained lean mass. Participants that lost lean mass had greater reductions in BMI [−0.77 (95% CI: −1.21, −0.33) v. +1.07 (95% CI: 0.56, 1.59)], greater reductions in FMI [−0.17 (95% CI: −0.48, 0.14) v. +0.46 (95% CI: 0.08, 0.83) p = 0.07] and a greater odds of having a reduction in FMI [OR: 2.30 (1.31, 4.05) p = 0.004], and had declining leptin levels and visceral fat area. Associations were strongest among those with high FMI at baseline. Conclusions In RA, loss of lean mass tends to occur in the context of a loss of weight and a loss of both total and visceral adiposity. These observations help to inform our understanding of the mechanisms leading to loss of muscle and rheumatoid cachexia in RA as well as to inform potential screening practices.

Comparative Effectiveness of Antihypertensive Medications in Children With Chronic Kidney Disease

JAMA Pediatrics · 2026-03-16 · 1 citations

Importance: Hypertension is a major modifiable factor for kidney function decline in chronic kidney disease (CKD). Comparative trials of antihypertensive medications in pediatric CKD are lacking. Objective: To evaluate the comparative effectiveness of renin-angiotensin-aldosterone system inhibition (RAASi) vs calcium channel blockade (CCB), the most widely used first-line antihypertensive treatment approaches in pediatric CKD, on preservation of kidney function. Design, Setting, and Participants: Using target trial emulation methods, this comparative-effectiveness study emulated a pragmatic, open-label clinical trial using electronic health record data from the Preserving Kidney Function in Children with CKD (PRESERVE) study from January 2009 through December 2020. Thirteen health care institutions from 5 PCORnet Clinical Research Networks were represented. Children and adolescents aged 2 to 20.9 years with CKD stage 2-4 and systolic blood pressure higher than the 90th percentile or with a hypertension diagnosis who initiated treatment with RAASi or CCB were included. Exclusion criteria included kidney replacement therapy, renal artery stenosis, malignancy, and pregnancy. Data analysis was completed in July 2025. Exposures: Incident RAASi or CCB treatment. Randomization was emulated by propensity score weighting to balance groups on sociodemographic factors, institution, year, CKD etiology, proteinuria, CKD stage, obesity, health care use, medications, comorbidities, and blood pressure control (percentage of time at greater than the 90th percentile). Main Outcomes and Measures: The primary outcome was progression to kidney replacement therapy within 2 years of follow-up, ascertained through linkage with the United States Renal Data System. The secondary outcome was a composite of kidney replacement therapy, 50% decline in estimated glomerular filtration rate, or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. Cox proportional hazards regression with propensity score stratification was used to estimate adjusted hazard ratios (aHRs) in the intention-to-treat analysis. Adjusted analyses also compared systolic blood pressure control within 2 years of follow-up. Results: Of 2762 children and adolescents, 1757 initiated RAASi (median [IQR] age, 13.1 [9.2-15.5] years; 897 [51.1%] male) and 1005 initiated CCB (median [IQR] age, 12.6 [8.4-15.3] years; 500 [49.8%] male). In adjusted analyses, RAASi was associated with reduced risk of both kidney replacement therapy (aHR, 0.58; 95% CI, 0.40-0.84, P = .004) and the secondary composite outcome (aHR, 0.67; 95% CI, 0.53-0.83). Systolic blood pressure control was better with RAASi than CCB (29% vs 39% of time >90th percentile). Conclusions and Relevance: In this comparative-effectiveness study, RAASi was associated with lower risk of CKD progression and better blood pressure control compared to CCB. Findings support first-line use of RAASi for antihypertensive treatment in pediatric CKD.

Changes in Three-Dimensional Volumetric Liver Fat Fraction after Cure of Chronic Hepatitis C Infection with Direct-Acting Antivirals

Open Forum Infectious Diseases · 2026-01-11

Abstract Background It remains unclear if cure of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) leads to change in liver fat fraction and if this change differs from people without HCV observed over similar time. We evaluated the change in three-dimensional volumetric liver fat fraction by magnetic resonance imaging (MRI) prior to DAA treatment and 18 months following initiation and compared changes in uninfected controls over 18 months. Methods We conducted a cohort study of 35 participants who initiated DAAs and achieved cure and 42 without HCV infection as controls. At enrollment and 18 months later, participants had measurements of height, body weight, and three-dimensional volumetric liver fat fraction and cross-sectional area of abdominal subcutaneous and visceral adipose tissue by MRI. Multivariable linear regression was used to estimate group differences in mean changes in liver fat fraction. Results Mean change in three-dimensional volumetric liver fat fraction between Months 0 and 18 was +2.89% (95% CI: + 0.89%, + 4.88%) among participants with cured HCV and +0.48% (95% CI: -1.02%, + 1.97%) among controls (between group difference p-value=0.05). After adjustment for age, sex, smoking, and change in body mass index, the mean difference in liver fat fraction change between Months 0 and 18 was +3.11% (95% CI: + 0.46%, + 5.76%; p = 0.022) higher for participants with HCV versus controls. Conclusions Three-dimensional volumetric liver fat fraction by MRI significantly increased between Months 0 and 18 following successful treatment of HCV infection, but this finding was not observed from Month 0 to 18 among participants without HCV infection.

Exercise Capacity, Endothelial Function, Muscle Mass, and Strength in Pediatric Patients With Fontan Circulation

CJC Pediatric and Congenital Heart Disease · 2025-11-01 · 2 citations

<h2>Abstract</h2><h3>Background</h3> Fontan circulation carries high morbidity and mortality, driven in part by impaired exercise capacity, muscle deficits, and endothelial dysfunction. In a pediatric cohort with Fontan circulation, we examined associations between exercise capacity, endothelial function, and muscle parameters before enrollment in a randomized exercise intervention. <h3>Methods</h3> Patients aged 8-19 years who have Fontan circulation were included. Exclusion criteria included New York Heart Association class IV, active illness, protein-losing enteropathy, pacemaker, or cognitive delay. Assessments included cardiopulmonary exercise testing (peak VO₂), endothelial function testing (reactive hyperemia index [RHI]), fasting lipid profile, dual-energy x-ray absorptiometry and dynamometry (muscle mass and strength), and functional movement screening (FMS). <h3>Results</h3> Among 137 participants (median age 12.7 years; 53% single right ventricle), median time since Fontan was 8.6 years. Peak VO₂ was 1402 ± 509 mL/min (75.7% ± 17.9% predicted; 31.1 ± 7.4 mL/kg/min indexed). RHI was 1.45 ± 0.6; NOx 22.2 ± 17.4 μmol/L. The low-density lipoprotein cholesterol level was 65.8 ± 18.9 mg/dL. Length-adjusted leg lean mass, handgrip strength, and leg extension strength <i>z</i> scores were –1.02 ± 1.0, –0.76 ± 0.9, and –0.70 ± 1.0, respectively. The FMS score averaged 11.9 ± 3.0. Peak VO₂ correlated with RHI (<i>r</i> = 0.50), lnRHI (<i>r</i> = 0.51), FMS (<i>r</i> = 0.30) (all <i>P</i> < 0.001), and length-adjusted leg lean mass <i>z</i> score (<i>r</i> = 0.25, <i>P</i> = 0.003). Indexed and percent-predicted peak VO₂ also correlated with FMS (<i>r</i> = 0.31 and 0.30, respectively) and high-density lipoprotein (<i>r</i> = 0.24 and <i>r</i> = 0.25, respectively). <h3>Conclusion</h3> In youth with Fontan circulation, lower aerobic capacity was associated with lower endothelial function, leg lean mass, strength, and mobility, underscoring the interdependence of cardiovascular, vascular, and musculoskeletal health. <h3>Clinical Trial</h3> NCT04195451

Molecularly Targeted Cancer Medications and Kidney Health

JAMA Network Open · 2025-11-06 · 2 citations

Importance: Oral molecularly targeted cancer medications are widely used. Product labels describe an increase in serum creatinine (sCr), potentially due to reversible inhibition of tubular creatinine secretion rather than acute kidney injury. Objective: To determine the 2-year incidence and relative rates of progressive kidney dysfunction in patients treated with molecularly targeted cancer medications associated with an acute change in sCr handling (pseudoacute kidney injury). Design, Setting, and Participants: Retrospective cohort study of adult patients throughout the San Francisco Bay area treated at Stanford Hospital and clinics since 2008 receiving cyclin dependent kinase 4 or 6 (CDK4/6) inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, and specific drugs within tyrosine kinases inhibitor subgroups with an available estimated glomerular filtration rate (eGFR) from days 1 to 60 after drug start compared with propensity score-matched patients without cancer. Exposure: Molecularly targeted cancer medications associated with an acute change in sCr. Main outcomes and measures: Progressive kidney dysfunction defined as a sustained 30% or more decline in eGFR or reaching end-stage kidney disease, accounting for a potentially reversible rise in sCr at drug start by defining baseline eGFR as the mean value from days 1 to 60 after drug start. Results: Among 5015 patients in the treated cohort, the median (IQR) age was 62 (51-72) years, 3264 (65%) were female, and the mean (SD) baseline eGFR before drug start was 87 (23) mL/min/1.73m2. Using cox proportional hazards regression models, the overall incidence and rate of progressive kidney dysfunction was higher in the treated cohort than in propensity-matched cohorts of patients without cancer (44 vs 38 per 1000 person-years; hazard ratio [HR], 1.4; 95% CI, 1.2-1.6). Rates of kidney dysfunction were higher among patients treated with CDK4/6 inhibitors (HR, 1.9; 95% CI, 1.4-2.6), estimated glomerular filtration rate inhibitors (HR, 1.8; 95% CI, 1.2-2.5), vascular endothelial growth factor receptor inhibitors (HR, 2.1; 95% CI, 1.6-2.7), and B-Raf inhibitors (HR, 1.9; 95% CI, 1.1-3.3) compared with controls. These higher rates persisted in patients without a 20% or more increase in sCr at drug start and without exposure to chemotherapy or immunotherapy. Conclusions and relevance: In this cohort study of patients treated with molecularly targeted anticancer medications associated with an acute rise in sCr, we observed higher incidence and relative rate for kidney dysfunction among treated patients, compared with matched cancer-free patients.

Use of Molecularly Targeted Cancer Medications and Kidney Health

Journal of the American Society of Nephrology · 2025-10-01

Changes in Bone Microarchitecture and Inflammatory Cytokines After Cure of Chronic Hepatitis C Infection With Direct-Acting Antiviral Therapy

Open Forum Infectious Diseases · 2025-08-29 · 1 citations

Abstract Background It remains unclear if cure of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) ameliorates HCV-related inflammation and bone deficits. We evaluated changes in cytokines and bone measurements by high-resolution peripheral quantitative computed tomography (HR-pQCT) prior to DAA treatment and 18 months following initiation and compared changes in uninfected controls over 18 months. Methods We conducted a cohort study of 40 participants who initiated DAAs and achieved cure and 48 without HCV as controls. At enrollment and 18 months later, participants had measurements of volumetric bone mineral density, cortical dimensions, and mechanical properties of the radius and tibia by HR-pQCT; visceral fat area and appendicular lean mass by whole-body dual-energy X-ray absorptiometry; and serum tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 18 (IL-18). Multivariable linear regression was used to estimate group differences in mean changes in bone measurements and cytokines. Results We observed no significant differences in month 0–18 changes in HR-pQCT measurements between participants with cured HCV and controls in unadjusted models or after adjustment for age, sex, appendicular lean mass index, visceral fat area, and smoking. Participants with cured HCV had decreases in IL-18 (mean change, −0.085 vs +0.086 log pg/mL; P &amp;lt; .001) and TNF-α (mean change, −0.050 vs +0.084 log pg/mL; P &amp;lt; .001), but not IL-6 (mean change, +0.108 vs +0.009 log pg/mL; P = .214) versus controls. Conclusions Participants with cured HCV had no significant changes in bone microarchitecture by HR-pQCT 18 months after DAA initiation compared with controls, but did have decreases in IL-18 and TNF-α versus controls.

Bone Health in Young Individuals with Primary Ciliary Dyskinesia: Insights from a Comparison with Cystic Fibrosis and Healthy Controls

Hormone Research in Paediatrics · 2025-11-17

INTRODUCTION: Bone health screening is established in cystic fibrosis (CF). Given the unknown status of bone quality in primary ciliary dyskinesia (PCD), these recommendations have not been adopted. We aimed to evaluate the bone phenotype in PCD compared to healthy controls and CF. METHODS: In this exploratory cross-sectional study, we assessed bone mineral density (BMD) at the whole body and lumbar spine using dual-energy X-ray absorptiometry (DXA), and tibial bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) in 15 individuals with PCD and 45 with CF, aged 12-20 years. Measures were compared to healthy controls matched one-to-one by pubertal stage and sex. Disease-to-healthy differences were compared between PCD and CF, and associations with body mass index (BMI), lean mass, and lung function were analysed. RESULTS: DXA-measured areal BMD and HR-pQCT-derived total volumetric BMD showed no differences between PCD and controls. HR-pQCT revealed reduced cortical thickness, area, and BMD at the ultra-distal tibia in PCD compared to controls. While PCD and CF did not differ, the PCD bone phenotype more closely resembled pancreatic-insufficient than pancreatic-sufficient CF. Dimensional cortical deficits were largely explained by BMI or lean mass, especially in CF, but remained reduced in PCD after adjustment, indicating potentially intrinsic disease-related alterations. Lung function did not clearly correlate with bone outcomes in PCD. CONCLUSION: Skeletal health appears compromised in young people with PCD. Despite mostly normal densitometry, tibial bone microarchitecture was altered. This study positions bone health as a research priority in PCD and supports the need for larger confirmatory studies.

Cystinosis is Associated with Deficits in Muscle Mass, Strength and Hip Bone Density in Children and Young Adults

Kidney360 · 2025-12-24

BACKGROUND: Cystinosis is associated with growth failure, myopathy and multiple risk factors for impaired bone development. The objectives of this study were to quantify muscle mass, muscle strength, and bone mineral density (BMD) in children and adults with cystinosis. METHODS: This cross-sectional study assessed DXA regional lean mass, spine and hip BMD, handgrip and leg strength in 38 participants with cystinosis (ages 5-37 years) and 289 healthy controls. All BMD, muscle mass and muscle strength measures were expressed as sex-specific Z-scores relative to age and adjusted for height Z-score or limb length. Linear regression models were used to assess muscle strength relative to muscle mass (muscle specific force) and determine the impact of adjusting BMD results for muscle status. RESULTS: Among adults, arm and leg lean mass (p < 0.001), handgrip strength (p < 0.001), proximal and distal leg strength (p < 0.001), muscle specific force (p < 0.01) and femoral neck and total hip BMD (p<0.001) were markedly low, compared with controls. On average, muscle strength was more than 2 SD below normal, due to both low muscle mass and poor muscle quality. Among the children and adolescents, upper extremity lean mass and grip strength were preserved. However, leg lean mass (p < 0.01), strength (p < 0.001), muscle specific force (p < 0.001) and femoral neck and total hip BMD (p < 0.01) were reduced, compared with controls, approaching deficits seen in adults. Adjustment for lean mass and muscle strength markedly attenuated the BMD deficits. CONCLUSIONS: Cystinosis is associated with deficits in muscle mass and strength that far exceed those observed in CKD alone and is associated with low proximal femur BMD. Future studies are needed to determine if physical activity or other interventions to address sarcopenia in cystinosis will improve physical function and bone strength.

Corticosteroid, Parathyroid Hormone, and Body Composition Associations With Bone Density and Structure Following Kidney Transplantation

American Journal of Kidney Diseases · 2025-11-06 · 1 citations