Enzymuria in gentamicin-induced kidney damage.

Area of Science:

• Nephrology
• Biochemistry
• Toxicology

Background:

• Gentamicin is a widely used antibiotic with known nephrotoxic potential.
• Early detection of gentamicin-induced kidney damage is crucial for preventing irreversible renal injury.
• Current biomarkers for kidney damage often appear late in the disease process.

Purpose of the Study:

• To evaluate lysosomal hydrolases as early biomarkers of gentamicin nephrotoxicity in a rat model.
• To compare the sensitivity of lysosomal hydrolases with traditional markers of kidney damage.

Main Methods:

• Rats were administered gentamicin (30 or 60 mg/kg/day) for 15 days.
• Urinary lysosomal hydrolases (beta-galactosidase, beta-n-acetyl-hexosaminidase, alpha-fucosidase) were measured.
• Other markers including proteinuria, urine osmolality, blood urea nitrogen, and creatinine clearance were assessed.
• Kidney tissue was analyzed using light and electron microscopy.

Main Results:

• Urinary levels of beta-galactosidase, beta-n-acetyl-hexosaminidase, and alpha-fucosidase significantly increased by day 3 in gentamicin-treated rats.
• These enzyme elevations occurred before changes in proteinuria, urine osmolality, or glomerular filtration rate markers.
• Histopathological changes, including proximal tubular necrosis, were observed later, starting around day 5 and peaking on day 10.
• Electron microscopy showed lysosomal abnormalities, such as myeloid bodies, in proximal tubular cells by day 5.

Conclusions:

• Urinary lysosomal hydrolases are sensitive and early indicators of gentamicin-induced kidney damage.
• Lysosomal enzymuria may reflect the early cellular damage occurring in proximal tubules.
• These findings suggest potential for lysosomal hydrolases as non-invasive early diagnostic markers for gentamicin nephrotoxicity.