Influence of Angiotensin Converting Enzyme I/D Polymorphism on Hemodynamic and Antioxidant Response to Long-Term Intradialytic Resistance Training in Patients With Chronic Kidney Disease: A Randomized Controlled Trial.

ABSTRACT: Corrêa, HdL, Deus, LA, Neves, RVP, Reis, AL, de Freitas, GS, de Araújo, TB, da Silva Barbosa, JM, Prestes, J, Simões, HG, Amorim, CE, dos Santos, MAP, Haro, A, de Melo, GF, Gadelha, AB, Neto, LS, and Rosa, TdS. Influence of angiotensin converting enzyme I/D polymorphism on hemodynamic and antioxidant response to long-term intradialytic resistance training in patients with chronic kidney disease: a randomized controlled trial. J Strength Cond Res 35(10): 2902-2909, 2021-The aim of the study was to verify the influence of Angiotensin-converting enzyme (ACE) I/D genotype on blood pressure, muscle mass, and redox balance response to long-term resistance training (RT) in end-stage renal disease patients. Three hundred and twenty subjects were randomized into 4 groups: II + ID control (II + ID CTL, n = 80), II + ID RT (II + ID RT, n = 79), DD control (DD CTL n = 83), and DD RT (DD RT, n = 78). The RT lasted 24 weeks with a frequency of 3 times per week, on alternative days. Each section consisted of 3 sets of 8-12 repetitions in 11 exercises, with training loads at 6 point (somewhat hard) to 8 point (hard) based on OMNI-RES scale and was prescribed during dialysis (intradialytic). Statistical significance was accepted with p < 0.05. The most relevant benefits in blood pressure were found for DD homozygotes (p < 0.0001), whereas allele I carriers displayed a higher increase in muscle mass (p < 0.0001). Hemodialysis clinics that already use RT for their patients could include the genotyping of ACE to identify the predisposal of the patients to respond to RT and to counteract kidney disease-related comorbidities.

Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans.

Directed cell migration and process outgrowth are vital to proper development of many metazoan tissues. These processes are dependent on reorganization of the actin cytoskeleton in response to external guidance cues. During development of the nervous system, the MIG-10/RIAM/Lamellipodin (MRL) signaling proteins are thought to transmit positional information from surface guidance cues to the actin polymerization machinery, and thus to promote polarized outgrowth of axons. In C. elegans, mutations in the MRL family member gene mig-10 result in animals that have defects in axon guidance, neuronal migration, and the outgrowth of the processes or 'canals' of the excretory cell, which is required for osmoregulation in the worm. In addition, mig-10 mutant animals have recently been shown to have defects in clustering of vesicles at the synapse. To determine additional molecular partners of MIG-10, we conducted a yeast two-hybrid screen using isoform MIG-10A as bait and isolated Abelson-interactor protein-1 (ABI-1). ABI-1, a downstream target of Abl non-receptor tyrosine kinase, is a member of the WAVE regulatory complex (WRC) involved in the initiation of actin polymerization. Further analysis using a co-immunoprecipitation system confirmed the interaction of MIG-10 and ABI-1 and showed that it requires the SH3 domain of ABI-1. Single mutants for mig-10 and abi-1 displayed similar phenotypes of incomplete migration of the ALM neurons and truncated outgrowth of the excretory cell canals, suggesting that the ABI-1/MIG-10 interaction is relevant in vivo. Cell autonomous expression of MIG-10 isoforms rescued both the neuronal migration and the canal outgrowth defects, showing that MIG-10 functions autonomously in the ALM neurons and the excretory cell. These results suggest that MIG-10 and ABI-1 interact physically to promote cell migration and process outgrowth in vivo. In the excretory canal, ABI-1 is thought to act downstream of UNC-53/NAV2, linking this large scaffolding protein to actin polymerization during excretory canal outgrowth. abi-1(RNAi) enhanced the excretory canal truncation observed in mig-10 mutants, while double mutant analysis between unc-53 and mig-10 showed no increased truncation of the posterior canal beyond that observed in mig-10 mutants. Morphological analysis of mig-10 and unc-53 mutants showed that these genes regulate canal diameter as well as its length, suggesting that defective lumen formation may be linked to the ability of the excretory canal to grow out longitudinally. Taken together, our results suggest that MIG-10, UNC-53, and ABI-1 act sequentially to mediate excretory cell process outgrowth.

The effects of home-based progressive resistance training in chronic kidney disease patients.

INTRODUCTION: Faced with lockdowns, it was mandatory the development of supervised home-based RT protocols to keep patients with chronic kidney disease engaged in programs. Nonetheless, there is a lack of scientific literature regarding its effects on patients. PURPOSE: To investigate the effects of a supervised home-based progressive resistance training program on functional performance, bone mineral density, renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, redox balance, and the modulation of exerkines in patients with CKD in stage 2. METHODS: Patients (n = 31) were randomized and allocated into the control group (CTL; n = 15; 58.07 ± 5.22 yrs) or resistance training group (RT; n = 16; 57.94 ± 2.74 yrs). RT group performed 22 weeks of supervised progressive home-based resistance exercises. Bone mineral density, anthropometric measurements, and functional performance were assessed. Venous blood samples were collected at baseline and after the intervention for the analysis of markers of renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, and redox balance. RESULTS: Twenty-two weeks of home-based RT were effective in improving (P < 0.05) functional performance, bone mineral density, uremic profile, ADMA, inflammatory markers, the Klotho-FGF23 axis, glycemic homeostasis markers, and exerkines. These improvements were accompanied by higher concentrations of exerkines and anti-inflammatory cytokines. RT group displayed a decrease in cases of osteopenia after the intervention (RT: 50 % vs. CTL: 86.7 %; X2 = 4.763; P = 0.029). CONCLUSION: Results provide new evidence that supervised home-based progressive RT may be a relevant intervention to attenuate the progression of CKD and improve functional capacity, bone mineral density, and the immunometabolic profile. These improvements are associated with positive modulation of several exerkines.

Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study.

Background: The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample. Methods: 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05. Results: We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue. Conclusion: There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial 'U1111-1237-8231'. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

Dynamic not isometric training blunts osteo-renal disease and improves the sclerostin/FGF23/Klotho axis in maintenance hemodialysis patients: a randomized clinical trial.

This study compared the effectiveness of dynamic resistance training (DRT) versus isometric RT (IRT) on osteogenesis and hormonal mechanisms involved in maintenance hemodialysis (MHD) patients. One hundred and ninety-three MHD patients were randomized into three groups: control (CTL) (n = 60), DRT (n = 66), and IRT (n = 67). A first visit was required for an anamnesis to evaluate the number of medications, biochemical, and anthropometric measurements (dialysis adequacy, creatinine, urea, body mass, height, and body mass index). Grip strength, bone mineral density (BMD), and renal-bone markers were assessed pre- and postprotocol. The DRT and IRT training was 6 mo with a frequency of three times per week, on alternate days. Each training session consisted of three sets of 8 to 12 repetitions at lower and moderate intensities. Both training sessions were prescribed approximately 1 h prior to dialysis. Statistical significances were adopted with P < 0.05. There was a greater dropout in the IRT group (24%) as compared with the DRT group (14%), which in turn had less adverse clinical effects (67%, 24%, and 61% for CTL, DRT, and IRT, respectively). DRT promoted gains in BMD in different body locations, in addition to increasing pro-osteogenic factors (Klotho and calcitriol) and reducing those related to bone loss, such as sclerostin, FGF23, and PTH. There was an improvement in Ca × PO43 for DRT, whereas these benefits did not occur in the IRT group (P < 0.05). These novel findings suggest that the DRT generates biopositive adaptations in bone tissue in MHD and can be used as a nonpharmacological strategy to improve BMD.NEW & NOTEWORTHY This study shows, for the first time, the effect of dynamic and isometric resistance training on bone mineral density in hemodialysis patients, providing a new understanding of the possible participation of the sclerostin/FGF23/Klotho axis, vitD, PTH, and calcium × phosphate product in this process. However, isometric resistance training may not be sufficient to induce these benefits. Therefore, this study supports the potential therapeutic role of dynamic resistance training counteracting chronic kidney disease-mineral and bone disorder.