Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease

Background Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients. Methods Inclusion criteria for CKD patients were age $\ge$ 60 years old and glomerular filtration rate (GFR) < 45 mL/ min/1.73 m 2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m 2 , age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD 50 , RFD 75 , RFD 100 , RFD 150 and RFD 200 , respectively), peak RFD (RFD peak in absolute; NRFD peak normalized), timeto-peak RFD (t-RFD peak) and the relative force at RFD peak (MVF-RFD peak). A statistical parametric mapping approach was performed on the force, impulse and RFD-time curves. The integrated sEMG with time at 0-30, 0-50, 0-100 and 0-200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex. Results The cohort of 159 individuals had a median age of 69 (9 IQR) years and body mass index was 27.6 (6.2 IQR) kg/ m 2. Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFD peak (P = 0.009; $\eta$ 2 p = 0.034) and RFD 75 and RFD 100 (for both P < 0.001; $\eta$ 2 p = 0.068 and 0.064). The onedimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0-100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0-200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 0.421) time windows. Controls showed greater decrease of sEMG than CKD patients in the 0-30 ms (P = 0.020, Cohen's d = 0.533) and 0-50 ms (P = 0.010, Cohen's d = 0.640) time windows. As opposite to females, males showed almost the same differences between groups. Conclusions Our study is the first to show that CKD patients have higher fatigability than controls, which may be associated with an impaired motor-unit recruitment, highlighting a neural drive disturbance with CKD. Further studies are needed to confirm these findings.Comment: Journal of Cachexia, Sarcopenia and Muscle, In pres

Outcomes in Living Donor Kidney Transplantation: The Role of Donor's Kidney Function

Introduction: Living donor kidney transplant (LDKT) is one of the best therapeutic options for end-stage kidney disease (ESKD). Guidelines identify different estimated glomerular filtration rate (eGFR) thresholds to determine the eligibility of donors. The aim of our study was to evaluate whether pretransplant donor eGFR was associated with kidney function in the recipient. Methods: We retrospectively studied LDKT recipients who received a kidney graft between September 1, 2005, and June 30, 2016 in the same transplant center in France and that had eGFR data available at 3, 12, 24, and 36 months posttransplant. Results: We studied 90 donor-recipient pairs. The average age at time of transplant was 51.47 ± 10.95 for donors and 43.04 ± 13.52 years for recipients. Donors' average eGFR was 91.99 ± 15.37 mL/min/1.73 m2. Donor's age and eGFR were significantly correlated (p &#x3c; 0.0001, r2 0.023). Donor's age and eGFR significantly correlated with recipient's eGFR at 3, 12, and 24 months posttransplant (age: p &#x3c; 0.001 at all intervals; eGFR p = 0.001, 0.003, and 0.016, respectively); at 36 months, only donor's age significantly correlated with recipient's eGFR. BMI, gender match, and year of kidney transplant did not correlate with graft function. In the multivariable analyses, donor's eGFR and donor's age were found to be associated with graft function; correlation with eGFR was lost at 36 months; and donor's age retained a strong correlation with graft function at all intervals (p &#x3c; 0.001). Conclusions: Donor's eGFR and age are strong predictors of recipient's kidney function at 3 years. We suggest that donor's eGFR should be clinically balanced with other determinants of kidney function and in particular with age

Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis

Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. Methods: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016–2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite “amyloid score” score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. Results: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p &lt; 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813–0.962; p &lt; 0.001). Conclusions: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA

Risk of Preeclampsia and Adverse Pregnancy Outcomes after Heterologous Egg Donation: Hypothesizing a Role for Kidney Function and Comorbidity

Background and objectives: Preeclampsia (PE) is a risk factor for kidney diseases; egg-donation (ED) increasingly used for overcoming fertility reduction, is a risk factor for PE. CKD is also a risk factor for PE. However, kidney function is not routinely assessed in ED pregnancies. Objective of the study is seeking to assess the importance of kidney function and maternal comorbidity in ED pregnancies. Design, setting, participants and measurements. Design: retrospective observational study from clinical charts. Setting: Sant&rsquo;Anna Hospital, Turin, Italy (over 7000 deliveries per year). Selection: cases: 296 singleton pregnancies from ED (gestation &gt; 24 weeks), who delivered January 2008&ndash;February 2019. Controls were selected from the TOrino Cagliari Observational Study (1407 low-risk singleton pregnancies 2009&ndash;2016). Measurements: Standard descriptive analysis. Logistic multiple regression analysis tested: PE; pregnancy-induced hypertension; preterm delivery; small for gestational age; explicatory variables: age; BMI; parity; comorbidity (kidney diseases; immunologic diseases; thyroid diseases; other). Delivery over time was analyzed according to Kaplan Meier; ROC (Relative Operating Characteristic) curves were tested for PE and pre-term delivery, employing serum creatinine and e-GFR as continuous variables. The analysis was performed with SPSS v.14.0 and MedCalc v.18. Results: In keeping with ED indications, maternal age was high (44 years). Comorbidity was common: at least one potential comorbid factor was found in about 40% of the cases (kidney disease: 3.7%, immunologic 6.4%, thyroid disease 18.9%, other-including hypertension, previous neoplasia and all other relevant diseases&mdash;10.8%). No difference in age, parity and BMI is observed in ED women with and without comorbidity. Patients with baseline renal disease or &ldquo;other&rdquo; comorbidity had a higher risk of developing PE or preterm delivery after ED. PE was recorded in 23% vs. 9%, OR: 2.513 (CI 1.066&ndash;5.923; p = 0.039); preterm delivery: 30.2% vs. 14%, OR 2.565 (CI: 1.198&ndash;5.488; p = 0.044). Limiting the analysis to 124 cases (41.9%) with available serum creatinine measurement, higher serum creatinine (dichotomised at the median: 0.67 mg/dL) was correlated with risk of PE (multivariate OR 17.277 (CI: 5.125&ndash;58.238)) and preterm delivery (multivariate OR 2.545 (CI: 1.100&ndash;5.892). Conclusions: Within the limits of a retrospective analysis, this study suggests that the risk of PE after ED is modulated by comorbidity. While the cause effect relationship is difficult to ascertain, the relationship between serum creatinine and outcomes suggests that more attention is needed to baseline kidney function and comorbidity

Caractérisation physiopathologique de la fonction neuromusculaire de patients à comorbidités multiples atteints d'insuffisance rénale chronique avancée, pour l'implémentation d'une activité physique adaptée

Patients suffering from chronic kidney disease (CKD) have a reduced muscle mass and strength, often associated with profound fatigue. It has recently been recognized that the characterisation of the relationship between fatigue and neuromuscular fatigability makes it possible to improve our understanding of the fatigue symptom in these patients. The comprehension of this relationship allows to reinforce non-pharmaceutical therapeutic approaches using adapted physical activity interventions. There are conflicting results concerning neuromuscular fatigability in the literature. CKD patients display exercise limitations related to a disturbance of muscle homeostasis, but no other cause has been reported and the relationship with the fatigue symptom has never been studied.In this context, this work sought to shed light on the mechanisms of neuromuscular fatigability and its potential contribution to fatigue symptom in elderly patients suffering from CKD, compared to a control group matched for age, sex and diabetes status. The results show that CKD patients have greater neuromuscular fatigability than controls, specifically when it is quantified using the rate of force development, but not when assessed using maximal strength. Furthermore, CKD patients suffer from greater fatigue than controls, which is associated with a greater neuromuscular fatigability and a slower motor unit recruitment. These results suggest that CKD patients may manifest central impairment during exercise. In addition, the significant contribution of neuromuscular fatigability in the description of fatigue highlights the clinical usefulness of implementing adapted physical activity interventions in these patients to reduce fatigue and improve quality of life.Les patients souffrant d’'insuffisance rénale chronique avancée (IRCa) ont une diminution de la masse et de la force musculaire, souvent cumulée à une profonde fatigue. Il a été récemment reconnu que la quantification du lien entre fatigue et fatigabilité neuromusculaire permet d'améliorer la compréhension du symptôme de fatigue chez ces patients, tout en permettant de renforcer l'arsenal thérapeutique non-médicamenteux par le biais d'interventions en activité physique adaptée. Des résultats divisés concernant la fatigabilité neuromusculaire ressortent de la littérature. Les patients avec une IRCa ont des limitations à l'effort liées à une perturbation de l'homéostasie musculaire, mais aucune autre cause n'a été reportée et le lien avec le symptôme de fatigue n'a jamais été étudié. Dans ce contexte, ce travail de doctorat a cherché à quantifier la fatigabilité neuromusculaire, tout en mesurant sa contribution au symptôme de fatigue, chez des patients avec une IRCa par rapport un des individus contrôles de même âge, sexe et prévalence de diabète. Les résultats montrent que les patients avec une IRCa ont une fatigabilité neuromusculaire plus importante que les contrôles, spécifiquement lorsqu'elle est évaluée à travers le taux de monté en force, mais pas avec la force maximale. De plus, les patients avec une IRCa souffrent d'une fatigue plus importante qui est associée à une perturbation du recrutement des unités motrices et à la fatigabilité neuromusculaire. Ces résultats suggèrent que les patients avec une IRCa développent des phénomènes centraux à l'effort. De plus, la fatigabilité neuromusculaire évaluée avec la force maximale contribue à la description de la fatigue, indiquant qu'une activité physique adaptée pourrait permettre d'améliorer le symptôme de fatigue et la qualité de vie

Master 1 IFEPSA - Programmation RStudio

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Leclercq et al., 2024 - ABE and PCA

R script of Leclercq et al., 2023 in order to perform Augmented Backward Elimination and Principal Component Analysi

TD - Néphrologie

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