Work

Caloric restriction alters early renal responses to reversible obstructive nephropathy in rats

Year: 2026

Type: article

Abstract: Obstructive nephropathy is a renal pathology caused by impaired urinary outflow. Although ureteral occlusion in clinical practice is often reversible, the recovery phase after obstruction relief remains incompletely understood and lacks mechanism-based interventions. Caloric restriction (CR) is widely considered a nephroprotective strategy and has shown therapeutic potential in several models of kidney injury. In this study, we investigated whether a 35% CR pretreatment for 4 weeks modulates the early postobstructive renal response in a rat model of reversible unilateral ureteral obstruction (R-UUO). Pretreatment with CR did not enhance early kidney recovery 24 h after restoration of urine flow, as evaluated by serum creatinine, urea, and renal injury markers. During this phase, CR also failed to improve fibrosis and tissue remodeling markers (α-SMA, MMP2, Tgfb1). However, CR was associated with reduced renal Ngal expression and a shift in the inflammatory response, characterized by lower neutrophil infiltration. Meanwhile, macrophage markers CD163, Cd206, and Tlr2 remained elevated. CR altered acetylation-related molecular response, including opposite shifts in acetylation of histone H3 and histone H4, increased SIRT3, and decreased SIRT1, and resulted in selective preservation of oxidative phosphorylation complex I. These data indicate that under severe postobstructive kidney injury, CR induces selective inflammatory and metabolic-epigenetic remodeling without clear early morphofunctional rescue. Mitochondrial function and epigenetic plasticity appear to be CR-responsive elements, while timing and severity of injury appear critical for manifestation of phenotypic nephroprotection. Thus, development of more targeted CR protocols or CR mimetics may be required to translate observed molecular shifts into morphofunctional benefit.

Source: FEBS Journal

DOI: 10.1111/febs.70744