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

Stem Cell Fate and Immunomodulation Promote Bone Regeneration via Composite Bio-Oss®/AviteneTM Biomaterial

Bone defects in maxillofacial regions lead to noticeable deformity and dysfunctions. Therefore, the use of biomaterials/scaffolds for maxillofacial bone regrowth has been attracting great interest from many surgical specialties and experts. Many approaches have been devised in order to create an optimal bone scaffold capable of achieving desirable degrees of bone integration and osteogenesis. Osteogenesis represents a complex physiological process involving multiple cooperating systems. A tight relationship between the immune and skeletal systems has lately been established using the concept of “osteoimmunology,” since various molecules, particularly those regulating immunological and inflammatory processes, are shared. Inflammatory mediators are now being implicated in bone remodeling, according to new scientific data. In this study, a profiler PCR array was employed to evaluate the expression of cytokines and chemokines in human adipose derived-mesenchymal stem cells (hASCs) cultured on porous hydroxylapatite (HA)/Collagen derived Bio-Oss® /Avitene scaffolds, up to day 21. In hASCs grown on the Bio-Oss® /Avitene biomaterial, 12 differentially expressed genes (DEGs) were found to be up-regulated, together with 12 DEG downregulated. Chemokine CCL2, which affects bone metabolism, tested down-regulated. Interestingly, the Bio-Oss® /Avitene induced the down-regulation of pro-inflammatory interleukin IL-6. In conclusion, our investigation carried out on the Bio-Oss® /Avitene scaffold indicates that it could be successfully employed in maxillofacial surgery. Indeed, this composite material has the advantage of being customized on the basis of the individual patients favoring a novel personalized medicine approach

Loss of renal function in the elderly italians: a physiologic or pathologic process?

Abstract BACKGROUND: Nowadays it seems that chronic kidney disease (CKD) is outbreaking, mostly in the elderly participants. The aim of this study was to assess the progression of CKD in different ages. METHODS: We conducted a monocentric, retrospective, observational study enrolling 116 patients afferent to our outpatient clinic. INCLUSION CRITERIA: age >18 years, follow-up ≥5 years, estimated glomerular filtration rate (eGFR) <60mL/min/1.73 m(2), and/or diagnosed renal disease and/or presence of renal damage. Patients were divided into four groups according to their age: 25-55 years (n = 27), 56-65 (25), 66-75 (42), and 76-87 (22). eGFR was calculated using the modification of diet in renal disease and the CKD-epidemiology collaboration formulas. RESULTS: Younger patients had a significantly longer follow-up and less comorbidities, evaluated by the cumulative illness rating scale score, compared with the other groups. There was no difference between creatinine at baseline and at the end-of-follow-up period among the groups. Even though renal function significantly decreased in all groups, we noticed a slower progression as the age increased, and the difference between basal and end-of-follow-up eGFR was minimal in the group of patients aged 76-87 years. Analyzing the eGFR of every ambulatory control plotted against the year of follow-up, we showed a more rapid loss of filtrate in the younger group. Instead, loss of renal function decreased as the age of patients increased. CONCLUSIONS: This study demonstrates that, in elderly Italian participants, progression of CKD occurs more slowly than in younger patients. This implies that we may probably face an epidemic of CKD but that most of elderly patients diagnosed with CKD may not evolve to end-stage renal disease and require renal replacement therapy

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

Of Mice and Men: The Effect of Maternal Protein Restriction on Offspring’s Kidney Health. Are Studies on Rodents Applicable to Chronic Kidney Disease Patients? A Narrative Review

In the almost 30 years that have passed since the postulation of the &ldquo;Developmental Origins of Health and Disease&rdquo; theory, it has been clearly demonstrated that a mother&rsquo;s dietary habits during pregnancy have potential consequences for her offspring that go far beyond in utero development. Protein malnutrition during pregnancy, for instance, can cause severe alterations ranging from intrauterine growth retardation to organ damage and increased susceptibility to hypertension, diabetes mellitus, cardiovascular diseases and chronic kidney disease (CKD) later in life both in experimental animals and humans. Conversely, a balanced mild protein restriction in patients affected by CKD has been shown to mitigate the biochemical derangements associated with kidney disease and even slow its progression. The first reports on the management of pregnant CKD women with a moderately protein-restricted plant-based diet appeared in the literature a few years ago. Today, this approach is still being debated, as is the optimal source of protein during gestation in CKD. The aim of this report is to critically review the available literature on the topic, focusing on the similarities and differences between animal and clinical studies

Spontaneously Low Protein Intake in Elderly CKD Patients: Myth or Reality? Analysis of Baseline Protein Intake in a Large Cohort of Patients with Advanced CKD

The recent guidelines on nutritional management of chronic kidney disease (CKD) advise a reduction in protein intake as early as CKD stage 3, regardless of age, to slow kidney function impairment. However, since elderly patients are usually considered as having a spontaneously reduced protein intake, nutritional interventions to reduce protein intake are often considered futile. This study aimed to assess the baseline protein intake of elderly CKD patients referred for nephrology care, and explore the need for dietary evaluations, focusing on the current recommendations for protein restriction in CKD. This is an observational study of CKD patients followed in the unit dedicated to advanced CKD patients in Le Mans, France. Patients with stages 3 to 5 not on dialysis were included. All patients were evaluated by an expert dietician to assess their baseline protein intake, whenever possible on the basis of a 7-days diet journal; when this was not available, dietary recall or analysis of delivered meals was employed. Demographic characteristics, underlying kidney disease, Charlson Comorbidity Index (CCI), Malnutrition-Inflammation Score (MIS), Subjective Global Assessment (SGA) and clinical and laboratory data were recorded. Between 15 November 2017 and 31 December 2020, 436 patients were evaluated in the unit. Their age distribution was as follows: &ldquo;young&rdquo;: &lt;60 (n = 62), &ldquo;young-old&rdquo;: 60&ndash;69 (n = 74), &ldquo;old&rdquo;: 70&ndash;79 (n = 108), &ldquo;old-old&rdquo;: 80&ndash;89 (n = 140) and &ldquo;oldest-old&rdquo;: &ge;90 (n = 54). The prevalence of vascular nephropathies was higher in patients older than 70 years compared to younger ones, as did CCI and MIS (p &lt; 0.001). Moderate nutritional impairment (SGA: B) was higher in elderly patients, reaching 53.7% at &ge;90, while less than 3% of patients in the overall cohort were classified as SGA C (p &lt; 0.001). The median protein intake was higher than the recommended one of 0.8 g/kg/day in all age groups; it was 1.2 g/kg/day in younger patients and 1.0 thereafter (p &lt; 0.001). Patient survival depended significantly on age (p &lt; 0.001) but not on baseline protein intake (p = 0.63), and younger patients were more likely to start dialysis during follow-up (p &lt; 0.001). Over half of the patients, including the old-old and oldest-old, were still on follow-up two years after referral and it was found that survival was only significantly associated with age and comorbidity and was not affected by baseline protein intake. Our study shows that most elderly patients, including old-old and extremely old CKD patients, are spontaneously on diets whose protein content is higher than recommended, and indicates there is a need for nutritional care for this population

Pregnancy and Kidney Diseases: Multidisciplinary Follow-Up and the Vicious Circles Involving Pregnancy and CKD, Preeclampsia, Preterm Delivery and the Kidneys

Thomas Addis, the father of nephrology, once wrote that a clinician is complex, “he is part craftsman, part practical scientist, and part historian” [...

Dietary Management of Chronic Kidney Disease and Secondary Hyperoxaluria in Patients with Short Bowel Syndrome and Type 3 Intestinal Failure

Short gut syndrome can lead to type 3 intestinal failure, and nutrition and hydration can only be achieved with parenteral nutrition (PN). While this is a lifesaving intervention, it carries short- and long-term complications leading to complex comorbidities, including chronic kidney disease. Through a patient with devastating inflammatory bowel disease&rsquo;s journey, this review article illustrates the effect of short gut and PN on kidney function, focusing on secondary hyperoxaluria and acute precipitants of glomerular filtration. In extensive small bowel resections colon in continuity promotes fluid reabsorption and hydration but predisposes to hyperoxaluria and stone disease through the impaired gut permeability and fat absorption. It is fundamental, therefore, for dietary intervention to maintain nutrition and prevent clinical deterioration (i.e., sarcopenia) but also to limit the progression of renal stone disease. Adaptation of both enteral and parenteral nutrition needs to be individualised, keeping in consideration not only patient comorbidities (short gut and jejunostomy, cirrhosis secondary to PN) but also patients&rsquo; wishes and lifestyle. A balanced multidisciplinary team (renal physician, gastroenterologist, dietician, clinical biochemist, pharmacist, etc.) plays a core role in managing complex patients, such as the one described in this review, to improve care and overall outcomes