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.