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Y. Iwashita1, K. Wataru2, A. Maeda3, S. Yamada1, K. Sugimoto4, J. Iiyama1
1Kumamoto Health Science University, Rehabilitation, Kumamoto, Japan, 2Sakurajyuji Hospital, Rehabilitation, Kumamoto, Japan, 3Kumamoto University Graduate School of Medical Sciences, Nephrology, Kumamoto, Japan, 4Kumamoto Health Science University Graduate School, Rehabilitation, Kumamoto, Japan
Background: In Japan, autosomal dominant polycystic kidney disease (ADPKD) affects approximately 31,000 individuals, necessitating dialysis by the age of 60 in nearly 50% of patients. Notably, delaying the initiation of dialysis is a crucial factor governing the patients’ quality of life and medical economy. In Japan, soaking the whole body in hot water has been a popular daily practice to induce healing. However, hyperthermia reportedly results in cell proliferation. In recent years, we have reported that mild systemic thermal stimulation (MTS) demonstrates a renoprotective effect in a chronic kidney disease mouse model.
Purpose: In this study, we evaluated the effects of MTS on renal function and cyst enlargement in a polycystic kidney disease (PKD) mouse model.
Methods: DBA/2FG-pcy mice (8 weeks, male, n = 9) were divided into a PKD+MTS group, a PKD+Su group receiving 4% sucrose water, and a PKD control group. For MTS intervention, mice were placed in a far-infrared device heated to 43°C for 10 min and then incubated at 37°C for 35 min twice weekly, for 4 weeks. In the PKD+Su group, mice were provided 4% sucrose water ad libitum overnight after the MTS intervention to prevent dehydration. At the end of experimentation, 24-h urine, blood, and renal samples were collected. Physiological, biochemical, and molecular analyses were performed. Statistical analyses were performed using one-way ANOVA, followed by Tukey’s post-hoc test. A P-value of less than 0.05 was considered statically significant.
Results: Among the three groups, no significant differences were observed in terms of food or water intake, body weight, urinary volume, blood urea nitrogen, and creatinine levels. Furthermore, no elevation in blood glucose levels was observed following the overnight ingestion of 4% sucrose water. The expansion of cysts, as observed in the control group, was reduced in the PKD+MTS group. In the PKD-MTS group, the expression of both extracellular-signal-regulated kinase (ERK) and heat shock protein (Hsp) 90, associated with cell proliferation, was significantly decreased when compared with the control group (ERK: p < 0.05; Hsp90: p < 0.01). However, no significant difference was observed in the expression of mammalian target of rapamycin and caspase3. Conversely, phosphorylated Hsp27 expression tended to increase in the PKD-MTS group when compared with the control (p = 0.10).
Conclusion(s): Repeated MTS for 4 weeks did not exacerbate renal function. Furthermore, repeated MTS can potentially alleviate PKD progression by suppressing the ERK pathway or Hsp90 expression.
Implications: Notably, repeated MTS could reduce the expression of Hsp90 and suppress the expansion of cysts following a 4-week MTS intervention in a PKD mouse model. Hence, MTS could be utilized as a potential non-pharmacotherapeutic intervention. Further long-term follow-ups and mechanistic elucidation are required.
Funding, acknowledgements: Not funded
Keywords: autosomal dominant polycystic kidney disease, mild systemic thermal stimulation, expansion of cysts
Topic: Professional issues
Did this work require ethics approval? Yes
Institution: Kumamoto Health Science University
Committee: Animal Experiment Committee
Ethics number: 44760
All authors, affiliations and abstracts have been published as submitted.
