title: Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.
abstract: BACKGROUND
  Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients.
  
  
  METHODS
  We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb).
  
  
  RESULTS
  Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night.
  
  
  CONCLUSIONS
  Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ishigaki
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. ohashi-n@hama-med.ac.jp.
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Isobe
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuji
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Iwakura
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Sakao
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: C054513:6-sulfatoxymelatonin; D008550:Melatonin
keywords: Blood pressure; Chronic kidney disease; Intrarenal renin–angiotensin system; Melatonin; Urinary 6-sulphatoxymelatonin; Urinary angiotensinogen