Chronic progressive renal lesions induced by lithium.

Area of Science:

• Nephrology
• Toxicology
• Pathology

Background:

• Lithium (Li) is a mood stabilizer with known renal side effects.
• Understanding the precise mechanisms and timeline of lithium-induced nephropathy is crucial for patient management.

Purpose of the Study:

• To investigate the histological and functional changes in the kidneys of New Zealand white rabbits following chronic lithium exposure.
• To determine the onset and progression of lithium-induced renal lesions.

Main Methods:

• Sequential open renal biopsies were performed on rabbits fed lithium (Li) or a control diet over 12 months.
• Histological analysis included quantitation of interstitial fibrosis, tubular atrophy, cast formation, glomerular sclerosis, and distal tubular changes.
• Macroscopic kidney examination and blood urea and serum creatinine levels were assessed.

Main Results:

• A distinctive lesion of cytoplasmic vacuolation and glycogen accumulation in distal tubules and collecting ducts was observed in lithium-fed rabbits from one month onwards.
• Chronic focal interstitial nephropathy, including fibrosis, tubular atrophy, and cast formation, showed significant differences compared to controls from one month.
• Distal tubular dilatation and microcyst formation were marked in the lithium group, progressing with exposure duration. Raised blood urea and serum creatinine were late findings.

Conclusions:

• Lithium administration induces chronic renal lesions in rabbits, characterized by specific distal tubular changes and progressive interstitial nephropathy.
• The observed renal alterations suggest a direct toxic effect of lithium on renal tubules and interstitium.
• The exact relationship between the observed tubular lesions and interstitial nephropathy requires further investigation.