title: High-tone external muscle stimulation in patients with acute kidney injury (AKI): beneficial effects on NO metabolism, asymmetric dimethylarginine, and endothelin-1.
abstract: OBJECTIVE
  The aim of this study was to assess potential effects of high-tone external muscle stimulation (HTEMS) on parameters of endothelial dysfunction (ED) in patients with acute kidney injury (AKI).
  
  
  BACKGROUND
  The bad outcome of AKI patients is markedly influenced by ED, microinflammation, oxidative stress and protein hypercatabolism. Recently, we have shown that intradialytic application of HTMS was associated with a faster resolution of AKI. Here, we investigated in the same cohort of patients whether parameters of ED such as nitric oxide (NO), asymmetric-dimethylarginine (ADMA), and endothelin 1 (ET-1) are modulated by HTEMS as compared to non-HTEMS-treated AKI patients.
  
  
  METHODS
  In a post-hoc study we analyzed plasma samples of the 34 AKI patients stage 5, of whom 17 underwent intradialytic HTEMS treatment while the other 17 served as AKI dialysis controls. Measurements included plasma nitrate and nitrite (NOx), ADMA, ET-1 and were performed before and on days 3, 7, 14, 21, and 28 after start of daily dialysis. Additional 16 healthy volunteers served as controls.
  
  
  RESULTS
  Initially, in both AKI groups NOx levels were markedly lower and ADMA and ET-1 levels were higher compared to the healthy controls. After initiation of daily hemodialysis the HTEMS group showed a faster improvement of NOx and ET-1 (after 1 week) and ADMA levels (after 2 weeks) compared to the No- HTEMS group. After 2 weeks, all parameters of the HTEMS group were not different from healthy controls, while the No-HTEMSAKI group needed 3 - 4 weeks.
  
  
  CONCLUSIONS
  Our findings suggest for the first time that in AKI patients, application of HTEMS is associated with a faster normalization of lowered NOx and elevated ADMA and ET-1 plasma levels. We hypothesize that the more rapid amelioration of these parameters in the HTEMS group contributed to the accelerated recovery of AKI. With regard to the small study groups with different causes of AKI, investigations in a greater number of AKI patients is required.
authors.forename: Biagio
authors.initials: B
authors.lastname: Di Iorio
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
authors.forename: Lucia
authors.initials: L
authors.lastname: Di Micco
authors.forename: Simona
authors.initials: S
authors.lastname: Adesso
authors.forename: Antonella
authors.initials: A
authors.lastname: De Blasio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Autore
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Sirico
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Fazeli
authors.forename: August
authors.initials: A
authors.lastname: Heidland
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015331:Cohort Studies; D004599:Electric Stimulation Therapy; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D007866:Leg; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal; D009569:Nitric Oxide / Q000378:metabolism*; D006435:Renal Dialysis
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine