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Effect of a Supervised Peridialytic Exercise Program on Serum Asymmetric Dimethylarginine in Maintenance Hemodialysis Patients.

ABSTRACT: End-stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have alarmingly high atherosclerotic cardiovascular disease morbidity and mortality. Nitric oxide (NO) is the principal endogenous antiatherosclerotic molecule. Increased asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, was strongly implicated in endothelial dysfunction, premature atherosclerosis, vascular events, and mortality. Regular physical exercise effectively decreased serum ADMA in several patient cohorts, but this potential benefit has not been specifically explored among MHD patients. Forty-four middle-aged ESRD patients treated with thrice-weekly MHD for ?6 months completed a 6-months regimen of peridialytic lower limb exercise comprising predialytic 10-12 stretching cycles and 20-30 minutes of intradialytic pedaling cycles. Before and after the study, predialytic haemoglobin, serum ADMA, urea, creatinine, calcium, phosphorus, and C-reactive protein (CRP) were measured. Dialysis adequacy was assessed by single-pool Kt/V. The average total physical activity (PA) level was assessed by the International Physical Activity Questionnaire (IPAQ). P values <0.05 denoted a statistical significance. The overall level of PA, on both categorical and continuous scales, has significantly increased after application of the exercise program. However, S. ADMA increased from a median of 2375 to 3000?ng/mL (P=0.016). Thirty-one patients sustained an increase in S. ADMA (ADMA_Inc), whereas 13 patients had a declining or stable S. ADMA (ADMA_Dec). Compared with ADMA_Inc, ADMA_Dec patients had significantly higher Kt/V (P=0.02), higher grade of the basal general PA level (P=0.017), and significantly fewer intradialytic hypotension episodes (IDHs) (P=0.019). The increase in the S. ADMA and the poststudy S. ADMA level had statistically significant positive correlations with the number of IDHs (r?=?0.401, P=0.007 and r?=?0.305, P=0.044, respectively). A 6-month program of combined aerobic and resistance peridialytic exercise failed to reduce S. ADMA in most MHD patients studied. A modest S. ADMA decline, however, occurred in patients with higher basal PA levels, higher Kt/V, and less IDHs. A potential exercise benefit may be promoted by a multidisciplinary approach targeting increased PA, improved dialysis efficiency, and prevention of IDHs.

SUBMITTER: Ammar YA

PROVIDER: S-EPMC7604598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Effect of a Supervised Peridialytic Exercise Program on Serum Asymmetric Dimethylarginine in Maintenance Hemodialysis Patients.

Ammar Yaser A YA Awad Ahmad A

International journal of nephrology 20201024

End-stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have alarmingly high atherosclerotic cardiovascular disease morbidity and mortality. Nitric oxide (NO) is the principal endogenous antiatherosclerotic molecule. Increased asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, was strongly implicated in endothelial dysfunction, premature atherosclerosis, vascular events, and mortality. Regular physical exercise effectively decreased serum ADMA i ...[more]

PMID: 33163233

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Project description:Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients.Post hoc analysis of the Hemodialysis (HEMO) Study.1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.ADMA and SDMA measured in stored specimens.Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function).Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2?mol/L) and SDMA levels (4.3±1.4?mol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 ?mol/L), the highest ADMA quintile (?1.07?mol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).Single time-point measurement of ADMA and SDMA.ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.

Project description:Background and objectivesLevels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.Design, setting, participants, & measurementsAsymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.ResultsMean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P<0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).ConclusionsAfrican Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.

Project description:BackgroundPeople receiving hemodialysis experience high symptom burden that contributes to low functional status and poor health-related quality of life. Management of symptoms is a priority for individuals receiving hemodialysis but limited effective treatments exist. There is emerging evidence that exercise programming can improve several common dialysis-related symptoms.ObjectiveThe primary aim of this study is to evaluate the effect of an exercise rehabilitation program on symptom burden in individuals receiving maintenance hemodialysis.DesignMulticenter, randomized controlled, 1:1 parallel, open label, prospective blinded end point trial.SettingThree facility-based hemodialysis units in Winnipeg, Manitoba, Canada.ParticipantsAdults aged 18 years or older with end-stage kidney disease receiving facility-based maintenance hemodialysis for more than 3 months, with at least 1 dialysis-related symptom as indicated by the Dialysis Symptom Index (DSI) severity score >0 (n = 150).InterventionSupervised 26-week exercise rehabilitation program and 60 minutes of cycling during hemodialysis thrice weekly. Exercise intensity and duration were supervised and individualized by the kinesiologist as per participant baseline physical function with gradual progression over the course of the intervention.ControlUsual hemodialysis care (no exercise program).MeasurementsOur primary outcome is change in symptom burden at 12 weeks as measured by the DSI severity score. Secondary outcomes include change in modified DSI severity score (includes 10 symptoms most plausible to improve with exercise), change in DSI severity score at 26 and 52 weeks; time to recover post-hemodialysis; health-related quality of life measured using EuroQol (EQ)-5D-5L; physical activity behavior measured by self-report (Godin-Shepherd questionnaire) and triaxial accelerometry; exercise capacity (shuttle walk test); frailty (Fried); self-efficacy for exercise; and 1-year hospitalization and mortality.MethodsChange in primary outcome will be compared between groups by independent 2-tailed t test or Mann-Whitney U test depending on data distribution and using generalized linear mixed models, with study time point as a random effect and adjusted for baseline DSI score. Similarly, change in secondary outcomes will be compared between groups over time using appropriate parametric and nonparametric statistical tests depending on data type and distribution.LimitationsThe COVID-19 pandemic restrictions on clinical research at our institution delayed completion of target recruitment and prevented collection of accelerometry and physical function outcome data for 15 months until restrictions were lifted.ConclusionsThe application of an exercise rehabilitation program to improve symptom burden in individuals on hemodialysis may ameliorate common symptoms observed in individuals on hemodialysis and result in improved quality of life and reduced disability and morbidity over the long term. Importantly, this pragmatic study, with a standardized exercise intervention that is adaptable to baseline physical function, addresses an important gap in both clinical care of hemodialysis patients and our current knowledge.

Dataset Information

Effect of a Supervised Peridialytic Exercise Program on Serum Asymmetric Dimethylarginine in Maintenance Hemodialysis Patients.

Publications

Effect of a Supervised Peridialytic Exercise Program on Serum Asymmetric Dimethylarginine in Maintenance Hemodialysis Patients.

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