Renal resistance to mercuric chloride toxicity during prolonged exposure in rats

An attempt was made to develop a model of chronic renal disease in the rat through repeated administration of a nephrotoxin specific for proximal tubular epithelium. Mercuric chloride was administered by subcutaneous injection in gradually increasing amounts over a period of 21 weeks. The dose ranged from 1.125 mg/kg once a week to 2.0 mg/kg twice a week. Measured parameters of renal function include plasma urea nitrogen, plasma creatinine, 24-hour urine output volume, and 24-hour urinary protein excretion. When compared to their own pretreatment values and those of the age/weight-matched control animals, the mercuric chloride-treated rats exhibited no significant abnormalities in these parameters of kidney function with the exception of a mild proteinuria at 21 weeks. Light microscopic examination of the kidneys of the mercury-treated rats revealed mild tubular, interstitial, and glomerular lesions which were significantly worse than those in the kidneys of the controls. This study demonstrates the ability of the kidney to sustain a considerable degree of resistance to inorganic mercury toxicity when exposure is continuous over a prolonged period of time. It also demonstrates the inability of commonly measured clinical laboratory parameters of kidney function to identify the effects of chronic mercuric chloride toxicity in the rat.