Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease

Area of Science:

• Nephrology
• Renal Pathology
• Translational Medicine

Background:

• Chronic kidney disease (CKD) progression is understood, but reversibility remains unclear.
• Assessing kidney recovery requires models that capture both functional and structural changes.

Purpose of the Study:

• To analyze kidney recovery and disease-modifying interventions in murine CKD models.
• To evaluate the discrepancy between functional recovery and histological damage in CKD.

Main Methods:

• Adapted a 2,8-dihydroxyadenine (2,8-DHA) crystal-induced nephropathy model for recovery studies.
• Utilized deep-learning-based histology to analyze glomeruli and tubules.
• Confirmed findings in a reversible unilateral ureteral obstruction model.

Main Results:

• Functional recovery was observed within two weeks, but tubular injury, inflammation, and fibrosis persisted.
• Histologic analysis revealed significant tubular dilation, atrophy, and irreversible nephron loss.
• High fluid intake prevented disease but was only therapeutic in moderate CKD, with medullary injury often overlooked.

Conclusions:

• Kidney recovery from CKD involves ongoing tissue injury and nephron loss not reflected by standard function tests.
• Current functional measures may overestimate kidney healing.
• Development of biomarkers for intra-kidney tissue injury is crucial for accurate assessment of renal recovery.