title: Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.
abstract: Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Department of Rehabilitation, Kumamoto Health Science University, Kumamoto, Japan; and.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Iwashita
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; ktakasea@kumamoto-u.ac.jp.
authors.forename: Takashige
authors.identifier: 0000-0003-3507-4328
authors.initials: T
authors.lastname: Kuwabara
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Manabu
authors.initials: M
authors.lastname: Hayata
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kakizoe
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Rehabilitation, Kumamoto Health Science University, Kumamoto, Japan; and.
authors.forename: Junichi
authors.initials: J
authors.lastname: Iiyama
authors.affiliation: Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Masashi
authors.initials: M
authors.lastname: Mukoyama
mesh_terms: D000419:Albuminuria / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced / Q000379:methods*; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D054834:Lipocalins / Q000652:urine; D008297:Male; D051379:Mice; D009392:Nephrectomy; D018384:Oxidative Stress / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D054834:Lipocalins; D003404:Creatinine
keywords: apoptosis; hyperthermia; mild thermal stimulation; oxidative stress; tubular injury