Step length and fall risk in adults with chronic kidney disease: a pilot study.

BACKGROUND: Patients with chronic kidney disease commonly experience gait abnormalities, which predispose to falls and fall-related injuries. An unmet need is the development of improved methods for detecting patients at high risk of these complications, using tools that are feasible to implement in nephrology practice. Our prior work suggested step length could be such a marker. Here we explored the use of step length as a marker of gait impairment and fall risk in adults with chronic kidney disease. METHODS: We performed gait assessments in 2 prospective studies of 82 patients with stage 4 and 5 chronic kidney disease (n = 33) or end-stage renal disease (ESRD) (n = 49). Gait speed and step length were evaluated during the 4-m walk component of the Short Physical Performance Battery (SPPB). Falls within 6 months prior to or following enrollment were identified by questionnaire. Associations of low step length (≤47.2 cm) and slow gait speed (≤0.8 m/s) with falls were examined using logistic regression models adjusted for demographics and diabetes and peripheral vascular disease status. RESULTS: Assessments of step length were highly reproducible (r = 0.88, p < 0.001 for duplicate measurements at the same visit; r = 0.78, p < 0.001 between baseline and 3-month evaluations). Patients with low step length had poorer physical function, including lower SPPB scores, slower gait speed, and lower handgrip strength. Although step length and gait speed were highly correlated (r = 0.73, p < 0.001), one-third (n = 14/43) of patients with low step length did not have slow gait speed. Low step length and slow gait speed were each independently associated with the likelihood of falls (odds ratio (OR) 3.90 (95% confidence interval (CI) 1.05-14.60) and OR 4.25 (95% CI 1.24-14.58), respectively). Compared with patients who exhibited neither deficit, those with both had a 6.55 (95% CI 1.40-30.71) times higher likelihood of falls, and the number of deficits was associated with a graded association with falls (p trend = 0.02). Effect estimates were similar after further adjustment for ESRD status. CONCLUSIONS: Step length and gait speed may contribute additively to the assessment of fall risk in a general adult nephrology population.

Skeletal muscle fibrosis is associated with decreased muscle inflammation and weakness in patients with chronic kidney disease.

Muscle dysfunction is an important cause of morbidity among patients with chronic kidney disease (CKD). Although muscle fibrosis is present in a CKD rodent model, its existence in humans and its impact on physical function are currently unknown. We examined isometric leg extension strength and measures of skeletal muscle fibrosis and inflammation in vastus lateralis muscle from CKD patients ( n = 10) and healthy, sedentary controls ( n = 10). Histochemistry and immunohistochemistry were used to assess muscle collagen and macrophage and fibro/adipogenic progenitor (FAP) cell populations, and RT-qPCR was used to assess muscle-specific inflammatory marker expression. Muscle collagen content was significantly greater in CKD compared with control (18.8 ± 2.1 vs. 11.7 ± 0.7% collagen area, P = 0.008), as was staining for collagen I, pro-collagen I, and a novel collagen-hybridizing peptide that binds remodeling collagen. Muscle collagen was inversely associated with leg extension strength in CKD ( r = -0.74, P = 0.01). FAP abundance was increased in CKD, was highly correlated with muscle collagen ( r = 0.84, P < 0.001), and was inversely associated with TNF-α expression ( r = -0.65, P = 0.003). TNF-α, CD68, CCL2, and CCL5 mRNA were significantly lower in CKD than control, despite higher serum TNF-α and IL-6. Immunohistochemistry confirmed fewer CD68+ and CD11b+ macrophages in CKD muscle. In conclusion, skeletal muscle collagen content is increased in humans with CKD and is associated with functional parameters. Muscle fibrosis correlated with increased FAP abundance, which may be due to insufficient macrophage-mediated TNF-α secretion. These data provide a foundation for future research elucidating the mechanisms responsible for this newly identified human muscle pathology.

QRS Morphology and the Risk of Ventricular Tachyarrhythmia in Cardiac Resynchronization Therapy Recipients.

BACKGROUND: There are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients. OBJECTIVES: The authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients. METHODS: The study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis. RESULTS: Among patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013). CONCLUSIONS: Our data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT.

Complications and Failure Modes of Covered Coronary Stents: Insights From the MAUDE Database.

BACKGROUND: Data on the mechanisms of failure of covered coronary stents [Graftmaster, PK Papyrus] are limited. METHODS: We queried the "Manufacturer and User Facility Device Experience" (MAUDE) database between August 2018 (when the PK Papyrus stent was FDA approved) and December 2020 for reports on covered coronary stents. RESULTS: We identified 299 reports in the MAUDE database (after excluding duplicates, peripheral vascular reports, and incomplete records) (Graftmaster n = 225, PK Papyrus n = 74). The most common mechanism of failure of covered stents was failure to deliver the stent (46.2%), followed by stent dislodgement (22.4%) and failure to seal the perforation (19.7%). Failure to deliver the stent was more often reported with Graftmaster compared with PK Papyrus (59.1% vs. 6.8%, p < 0.001). Stent dislodgement was more often reported with PK Papyrus compared with Graftmaster (75.7% vs. 4.9%, p < 0.001) and was managed by device retrieval or by crushing the stent. CONCLUSIONS: The most common failure mechanisms of covered stents are failure of delivery, stent dislodgement, and failure to seal the perforation. Failure of delivery was more common with Graftmaster, while stent dislodgement was more common with PK Papyrus. Further improvements in covered stent design are needed to optimize deliverability and minimize the risk of complications.

Muscle fibrosis and maladaptation occur progressively in CKD and are rescued by dialysis.

BACKGROUNDSkeletal muscle maladaptation accompanies chronic kidney disease (CKD) and negatively affects physical function. Emphasis in CKD has historically been placed on muscle fiber-intrinsic deficits, such as altered protein metabolism and atrophy. However, targeted treatment of fiber-intrinsic dysfunction has produced limited improvement, whereas alterations within the fiber-extrinsic environment have scarcely been examined.METHODSWe investigated alterations to the skeletal muscle interstitial environment with deep cellular phenotyping of biopsies from patients with CKD and age-matched controls and performed transcriptome profiling to define the molecular underpinnings of CKD-associated muscle impairments. We examined changes in muscle maladaptation following initiation of dialysis therapy for kidney failure.RESULTSPatients with CKD exhibited a progressive fibrotic muscle phenotype, which was associated with impaired regenerative capacity and lower vascular density. The severity of these deficits was strongly associated with the degree of kidney dysfunction. Consistent with these profound deficits, CKD was associated with broad alterations to the muscle transcriptome, including altered ECM organization, downregulated angiogenesis, and altered expression of pathways related to stem cell self-renewal. Remarkably, despite the seemingly advanced nature of this fibrotic transformation, dialysis treatment rescued these deficits, restoring a healthier muscle phenotype. Furthermore, after accounting for muscle atrophy, strength and endurance improved after dialysis initiation.CONCLUSIONThese data identify a dialysis-responsive muscle fibrotic phenotype in CKD and suggest the early dialysis window presents a unique opportunity of improved muscle regenerative capacity during which targeted interventions may achieve maximal impact.TRIAL REGISTRATIONNCT01452412FUNDINGNIH, NIH Clinical and Translational Science Awards (CTSA), and Einstein-Mount Sinai Diabetes Research Center.

Group-Based Care in Adults and Adolescents With Hypertension and CKD: A Feasibility Study.

RATIONALE & OBJECTIVE: Group-based care provides an opportunity to increase patient access to providers without increasing physician time and is effective in the management of chronic diseases in the general population. This model of care has not been investigated in chronic kidney disease (CKD). STUDY DESIGN: Randomized controlled trial in adults (n = 50); observational study in adolescents (n = 10). SETTING & PARTICIPANTS: Adults and adolescents with CKD and hypertension in the Bronx, NY. INTERVENTION: Group-based care (monthly sessions over 6 months) versus usual care in adults. All adolescents received group-based care and were analyzed separately. OUTCOMES: Participant attendance and satisfaction with group-based care were used to evaluate intervention feasibility. The primary clinical outcome was change in mean 24-hour ambulatory blood pressure. Secondary outcomes included physical activity, medication adherence, quality of life, and sodium intake as assessed by 24-hour urinary sodium excretion and food frequency questionnaires. RESULTS: Among adults randomly assigned to group-based care, attendance was high (77% of participants attended ≥3 sessions) and most reported higher satisfaction. Mean 24-hour ambulatory systolic blood pressure decreased by -4.2 (95% CI, -13.3 to 5.8) mm Hg in group-based care patients compared with usual care at 6 months but this was not statistically significant. Similarly, we did not detect significant differences in health-related behaviors (such as medication adherence, sodium intake, and physical activity) or quality-of-life measures between the 2 groups. Among the adolescents, attendance was very poor; self-reported satisfaction, although high, did not change from baseline compared with the 6-month follow-up. LIMITATIONS: Small study size, missing data. CONCLUSIONS: Group-based care is feasible and acceptable among adults with hypertension and CKD. However, a larger trial is needed to determine the effect on blood pressure and health-related behaviors. Patient participation may limit the effectiveness of group-based care models in adolescents. FUNDING: National Institutes of Health R34 DK102174. TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT02467894.

The Effects of Dairy Intake on Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

The incidence of type 2 diabetes mellitus (DM) has increased in the US over the last several years. The consumption of low-fat dairy foods has been linked with decreasing the risk of DM but studies have yet to show a clear correlation. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effects of dairy intake on homeostatic model assessment of insulin resistance (HOMA-IR), waist circumference, and body weight. In MEDLINE and Embase, we identified and reviewed 49 relevant RCTs: 30 had appropriate data format for inclusion in the meta-analysis. Using the Review Manager 5 software, we calculated the pooled standardized mean differences comparing dairy dietary interventions to control for our outcomes of interest. For HOMA-IR (794 individuals), we found a mean difference of -1.21 (95% CI -1.74 to -0.67; p-value < 0.00001; I2 = 92%). For waist circumference (1348 individuals), the mean difference was -1.09 cm (95% CI 1.68 to -0.58; p-value < 0.00001; I2 = 94%). For body weight (2362 individuals), the dairy intake intervention group weighed 0.42 kg less than control (p-value < 0.00001; I2 = 92%). Our findings suggest that dairy intake, especially low-fat dairy products, has a beneficial effect on HOMA-IR, waist circumference, and body weight. This could impact dietary recommendations to reduce DM risk.