Unilateral nephrectomy in the rat: effects on mercury handling and renal cortical subcellular distribution

As unilateral nephrectomy (UNX) is associated with enhanced mercuric chloride nephrotoxicity, studies were undertaken to characterize the effects of UNX on the tissue content, urinary excretion, and renal cortical subcellular distribution of mercury in the rat. Animals were studied immediately, 2 days or 14 days following UNX, during separate phases of compensatory renal hypertrophy. As compared to sham surgery controls, mercury content in renal cortex was higher in all UNX groups at 24 hr following injection and in the immediate and 2-day groups at 1 or 3 hr. However, UNX was not associated with any alteration in mercury content within outer or inner medulla, liver, plasma, or red blood cells. Subcellular distribution studies demonstrated that cytosolic mercury was uniformly elevated in all UNX groups at 1, 3, and 24 hr following injection while mercury bound to "metallothionein-like" proteins or free in the cytosol was increased only at 1 or 3 hr. Nuclear, mitochondrial, or microsomal mercury content was elevated in the animals studied immediately or 14 days after UNX at 3 or 24 hr following injection, while animals studied 2 days after UNX demonstrated a nearly uniform increase at 1, 3, and 24 hr. Single-kidney urinary mercury excretion was elevated in all UNX groups while excretion per gram kidney weight was increased only in the animals studied immediately or 2 days after surgery. These studies suggest that all phases of compensatory renal hypertrophy are associated with an enhanced content of mercury within the cell cytoplasm and in critical cellular organelles, which may explain the enhanced nephrotoxicity seen following UNX.