Metabolic and hormonal responses to chronic blood-flow restricted resistance training in chronic kidney disease: a randomized trial.

Maintenance of glycemic and lipemic homeostasis can limit the progression of diabetic kidney disease. Resistance training (RT) is effective in controlling glycemia and lipemia in kidney disease; however, the effect of RT with blood flow restriction (RT+BFR) on these metabolic factors has not been investigated. We aimed to verify if chronic (6 months) RT and RT+BFR performed by patients with stage-2 chronic kidney disease (CKD) improves their glycemic homeostasis and immunometabolic profiles. Patients with CKD under conservative treatment (n = 105 (33 females)) from both sexes were randomized into control (n = 35 (11 females); age 57.6 ± 5.2 years), RT (n = 35 (12 females); age 58.0 ± 6.2 years), and RT+BFR (n = 35 (10 females); 58.0 ± 6.4 years) groups. Chronic RT or RT+BFR (6 months) was performed 3 times per week on non-consecutive days with training loading adjusted every 2 months, RT 50%-60%-70% of 1RM, and RT+BFR 30%-40%+50% of 1RM and fixed repetition number. Renal function was estimated with the glomerular filtration rate and serum albumin level. Metabolic, hormonal, and inflammatory assessments were analyzed from blood samples. Six months of RT and RT+BFR were similarly effective in improving glucose homeostasis and hormone mediators of glucose uptake (e.g., irisin, adiponectin, and sirtuin-1), decreasing pro-inflammatory and fibrotic proteins, and attenuating the progression of estimated glomerular filtration rate. Thus, RT+BFR can be considered an additional exercise modality to be included in the treatment of patients with stage 2 chronic kidney disease. Trial registration number: U1111-1237-8231. URL: http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w/, no. RBR-3gpg5w. Novelty: Glycemic regulation induced by resistance training prevents the progression of CKD. Chronic RT and RT+BFR promote similar changes in glycemic regulation. RT and RT+BFR can be considered as non-pharmacological tools for the treatment of CKD.

Renoprotection Induced by Aerobic Training Is Dependent on Nitric Oxide Bioavailability in Obese Zucker Rats.

Aerobic training (AT) promotes several health benefits that may attenuate the progression of obesity associated diabetes. Since AT is an important nitric oxide (NO-) inducer mediating kidney-healthy phenotype, the present study is aimed at investigating the effects of AT on metabolic parameters, morphological, redox balance, inflammatory profile, and vasoactive peptides in the kidney of obese-diabetic Zucker rats receiving L-NAME (N(omega)-nitro-L-arginine methyl ester). Forty male Zucker rats (6 wk old) were assigned into four groups (n = 10, each): sedentary lean rats (CTL-Lean), sedentary obese rats (CTL-Obese), AT trained obese rats without blocking nitric oxide synthase (NOS) (Obese+AT), and obese-trained with NOS block (Obese+AT+L-NAME). AT groups ran 60 min in the maximal lactate steady state (MLSS), five days/wk/8 wk. Obese+AT rats improved glycemic homeostasis, SBP, aerobic capacity, renal mitochondria integrity, redox balance, inflammatory profile (e.g., TNF-α, CRP, IL-10, IL-4, and IL-17a), and molecules related to renal NO- metabolism (klotho/FGF23 axis, vasoactive peptides, renal histology, and reduced proteinuria). However, none of these positive outcomes were observed in CTL-Obese and Obese+AT+L-NAME (p < 0.0001) groups. Although Obese+AT+L-NAME lowered BP (compared with CTL-Obese; p < 0.0001), renal damage was observed after AT intervention. Furthermore, AT training under conditions of low NO- concentration increased signaling pathways associated with ACE-2/ANG1-7/MASr. We conclude that AT represents an important nonpharmacological intervention to improve kidney function in obese Zucker rats. However, these renal and metabolic benefits promoted by AT are dependent on NO- bioavailability and its underlying regulatory mechanisms.

Blood Flow Restriction Training Blunts Chronic Kidney Disease Progression in Humans.

PURPOSE: This study aimed to verify the effect of 6 months of periodized resistance training (RT) with and without blood flow restriction (BFR) in patients with stage 2 chronic kidney disease (CKD) on glomerular filtration rate (GFR), uremic parameters, cytokines, and klotho-fibroblast growth factor 23 (FGF23) axis. METHODS: A total of 105 subjects were randomized in three groups of 35 each: control (CTL), RT, and RT + BFR. A first visit was required for an anamnesis to evaluate the number of medications and anthropometric measurements (body weight, height, and body mass index). Muscle strength (one-repetition maximum) was assessed. Venous blood samples were collected at baseline and after 6 months of training in all patients for the analysis of markers of renal function and integrity, as well as for the determination of the inflammatory profile. Statistical significances were adopted with P < 0.05. RESULTS: Both training therapies attenuated the decline of GFR (P < 0.05). The majority of CTL patients declined to stage 3 CKD (88.5%), whereas fewer incidents were noted with RT (25.7%) and RT + BFR (17.1%). Improved uremic parameters as well as inflammation (IL-6, IL-10, IL-15, IL-17a, IL-18, and TNF-α) and klotho-FGF23 axis in RT and RT + BFR (P < 0.05) were observed. Monocyte chemoattractant protein 1 was not changed (P > 0.05) but presented a large effect size (Cohen's d), demonstrating a propensity for improvement. CONCLUSION: Six months of periodized RT with and without BFR in patients with stage 2 CKD attenuated the progression of the disease by maintaining GFR, improving uremic parameters, cytokine profile regulation, and klotho-FGF23 axis.

Low-load resistance training with blood flow restriction prevent renal function decline: The role of the redox balance, angiotensin 1-7 and vasopressin✰,✰✰.

AIMS: We sought to investigate the effect of resistance training (RT) and low-load RT with moderate blood flow restriction (RT+BFR) on blood pressure, exercise pressor response, redox balance and vasoactive peptides, body composition and muscle strength in patients with stage two of chronic kidney disease (CKD). METHODS: We conducted a 6-month randomized controlled exercise intervention in 90 male and female hypertensive CKD patients (58±9 years with estimated glomerular filtration rate (eGFR; of 66.1 ± 1.2 mL/kg/1.73m2). Participants were randomized to one of three groups (n = 30/group); control group (CTL), RT, and RT+BFR. RT and RT+BFR performed three weekly training sessions using similar periodization for six months (two-month mesocycles), but of different intensities. RESULTS: There was similarly effects between RT and RT+BFR in reducing systolic and diastolic blood pressure during daytime and 24hour period (RT: 10.4%; RT+BFR: 10.3% of decrease), fat mass, F2-isoprostanes, asymmetric dimethylarginine (ADMA) and vasopressin (p<0.05 pre-vs post). Also promoted the increase of angiotensin 1-7, nitric oxide (NO), catalase, Trolox equivalent and muscle strength (p<0.05). Both training models attenuated the decline of estimated glomerular filtration rate (p<0.0001 vs CTL). However, only RT+BFR was associated with lower discomfort during exercise (p<0.0001 pre-vs post). Statistical significance was considered with p < 0.05. CONCLUSION: These findings suggest low-load RT+BFR as a promising non-pharmacological strategy to control blood pressure, oxidative stress, vasoactive peptides, and consequently, attenuate the decrease of the eGFR.

Resistance training improves sleep quality, redox balance and inflammatory profile in maintenance hemodialysis patients: a randomized controlled trial.

Patients in maintenance hemodialisys (HD) present sleep disorders, increased inflammation, unbalanced redox profiles, and elevated biomarkers representing endothelial dysfunction. Resistance training (RT) has shown to mitigate the loss of muscle mass, strength, improve inflammatory profiles, and endothelial function while decreasing oxidative stress for those in HD. However, the relation between those factors and sleep quality are inadequately described. The aim of this study was to verify the effects of 3 months of RT on sleep quality, redox balance, nitric oxide (NO) bioavailability, inflammation profile, and asymmetric dimethylarginine (ADMA) in patients undergoing HD. Our primary goal was to describe the role of RT on sleep quality. Our secondary goal was to evaluate the effect of RT on NO, metabolism markers, and inflammatory and redox profiles as potential mechanisms to explain RT-induced sleep quality changes. Fifty-five men undergoing maintenance hemodialysis were randomized into either a control (CTL, n = 25) and RT group (RTG; n = 30). Participants in the RT group demonstrated an improvement in sleep pattern, redox, inflammatory profiles, and biomarkers of endothelial function (NO2- and ADMA). This group also increased muscle strength (total workload in RT exercises of upper and lower limbs). These findings support that RT may improve the clinical status of HD patients by improving their sleep quality, oxidative and inflammatory parameters.

l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease.

Chronic kidney disease (CKD) patients present L-arginine (L-arg) deficiency and L-arg supplementation has been used as a treatment. In addition, sarcopenia is another common problem in CKD population, resistance training (RT) is one of the conservative strategies developed to prevent CKD progression, and however there are no evidences of a combination of these two strategies to treat CKD outcomes. The aim of this study was to evaluate the effects of oral L-arg supplementation combined with RT in an experimental model of CKD. Twenty-five Munich-Wistar male rats, 8-week-old were divided in 5 groups: Sham (sedentary control), Nx (CKD sedentary), Nx L-arg (CKD sedentary supplemented with 2% of L-arg), Nx RT (CKD exercised) Nx RT + L-arg (CKD exercised and supplemented with 2% of L-arg). CKD model was obtained by a subtotal 5/6 nephrectomy. RT was performed on a ladder climbing, three weekly sessions on non-consecutive days, with an intensity of 70% maximum carrying capacity. They were submitted to RT and/or L-arg supplementation for 10 weeks. There was a significant improvement in muscle strength, renal function, anti-inflammatory cytokines, arginase metabolism and renal fibrosis after RT. However, the combination of RT and L-arg impaired all the improvements promoted by RT alone. The L-arg supplementation alone did not impair renal fibrosis and renal function. In conclusion, RT improved inflammatory balance, muscle strength, renal function and consequently decreased renal fibrosis. Nevertheless, the association with L-arg supplementation prevented all these effects promoted by RT.

Acute metabolic responses following different resistance exercise protocols.

Resistance exercise (RE) can be an excellent modality for glycemic control. Studies have demonstrated that a single RE session can reduce glycemia in subjects with or without diabetes. Little is known about the dose-response effect of RE on glycemic control. This study aimed to investigate the acute metabolic responses after different RE protocols. Eighty-nine males were separated into six groups that completed RE protocols: 2 sets of 18 repetitions (2 × 18 at 50% of 1-repetition maximum (1RM); n = 19); 3 sets of 12 repetitions (3 × 12 at 70% of 1RM; n = 14); 4 sets of 9 repetitions (4 × 9 at 80% of 1RM; n = 13); 6 sets of 6 repetitions (6 × 6 at 90% of 1RM; n = 19); circuit (2 × 18 at 50% of 1RM; n = 12); and a control session (n = 12). The exercise sequence consisted of 8 exercises. An oral glucose tolerance test was conducted with metabolic measurements immediately after each RE protocol and every 15 min until 120 min of recovery. All groups exhibited significantly lower values (p < 0.05) in the glucose area under the curve (AUC) when compared with control over a 120 min monitoring period. The 6 × 6 group showed a significantly lower glucose AUC versus the 3 × 12 and 4 × 9 groups (p = 0.004; p = 0.001, respectively). As for blood lactate, the control and 6 × 6 groups exhibited lower AUC values versus all other groups (p < 0.05), and AUC for glucose and lactate concentration showed a negative and significant correlation (r = -0.46; p < 0.0001). It appears that a combination of 9-12 repetitions per set and 3-4 sets per muscle group might be optimal for acute postprandial glucose control.