The effects of
ochratoxin A (OA), a nephrotoxic
mycotoxin, were investigated in partially nephrectomized (PN) rats (approximately 70% reduction in renal mass) following compensatory
hypertrophy of the renal remnant. Renal function stabilized 27 d after surgery. PN rats compensated for the initial loss of renal function except for glomerular filtration rate (GFR,
inulin clearance); this remained significantly impaired.
Sham-operated (SO) rats cleared
inulin and
p-aminohippurate (PAH) at rates of 3.84 and 7.49 ml/min, respectively, while compensated PN rats cleared
inulin at 2.51 and PAH at 8.84 ml/min. Daily administration of low levels of OA produced decreased urine osmolality and
body weight with a modest increase in urinary
protein of PN versus SO rats. OA-treated rats cleared
inulin,
creatinine, and PAH at rates significantly lower than nontreated controls: 0.89 and 1.96 ml/min for
inulin, 0.35 and 0.56 ml/min for
creatinine, and 2.29 and 6.23 ml/min for PAH. Histopathological findings indicated a considerable increase in renal tubular
necrosis and subcellular damage (i.e., loss of cytoplasmic ground substance, vacuolization, degeneration of mitochondria, and reorganization of endoplasmic reticulum) in PN animals versus controls, concurrent with alteration in renal function. These results verify that the nephrotoxic action of OA is elicited mainly in renal proximal tubules and is enhanced in the PN rat.