# Comparative Analysis of the Tolerance of Young and Old Kidneys to Injury in a Rat Model of Reversible Ureteral Obstruction

## TL;DR

This study compares how young and old rat kidneys respond to injury and recovery from urinary blockage, finding age-related differences in healing and damage.

## Contribution

The study reveals age-dependent differences in kidney injury recovery mechanisms, including autophagy, inflammation, and mitochondrial function.

## Key findings

- Young rats showed increased renal proliferation and profibrotic marker expression compared to old rats after injury.
- Old rats exhibited mitochondrial dysfunction and reduced autophagy activity following obstruction.
- Age-dependent differences in inflammation and tissue repair suggest the need for age-specific therapies.

## Abstract

Obstructive nephropathy is a common clinical condition caused by urinary retention. After urine flow is restored, kidney function is recovered. However, the effectiveness of this process can be influenced by many factors, including the age of the patient. In this study, we analyzed the following parameters in young and old rats subjected to a 3-day reversible unilateral ureteral obstruction (R-UUO): AKI severity, renal tissue proliferation and histology, inflammatory and fibrosis marker expression, as well as autophagosomal-lysosomal and mitochondrial function. Compared to old rats, young animals exhibited more pronounced renal tissue proliferation and higher expression of profibrotic markers (Col1a1, Fn1, Tgfb1, MMP2), but diminished expression of pro-inflammatory markers (Il1b, Tnfa, Cd32) in response to R-UUO. Additionally, young rats showed more pronounced activity of autophagy, as indicated by increased beclin-1 levels. R-UUO induced severe damage to the mitochondrial respiratory chain in old animals, as indicated by reduced complex I, IV, cytochrome c, VDAC protein levels, and impaired mitochondrial biogenesis (associated with decreased Pgc1a mRNA expression). Thus, we demonstrated that despite restored urine outflow, kidneys exhibited autophagy activation, inflammatory response, and mitochondrial dysfunction after R-UUO. Negative alterations in the kidney were age-dependent indicating necessity for therapeutic strategies optimization for patients of different ages.