Page 429 - The Toxicology of Fishes

The Osmoregulatory System 409

The Kidneys
The multifunctional role of the fish kidney, which combines the functions of lungs, kidneys, and intestines
of terrestrial vertebrates, is reflected by its complicated structure involving many different cell types and
an intricate vascular system. From the point of view of hydromineral regulation, the main function of
the kidneys in freshwater fish is the excretion of large volumes of osmotically accumulated water and
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the elimination of surplus ions extracted from the food, mainly K , sulfate, and phosphate. To limit the
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renal losses of valuable ions via the urine, intensive reabsorption of Na , Cl , Mg , and Ca takes place
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by means of transporting enzymes and exchangers in the epithelial cells lining the nephronic tubules,
collective tubules, and bladder. In seawater fish, the excretion of divalent ions taken up by drinking is
a major function of the kidneys. Water excretion has to be reduced as much as possible in a strongly
hyperosmotic environment, and this is effected mainly by reduction of the glomerular filtration rate
(Beyenbach, 1995). The basal parts of all the cells in the renal tubular epithelia as well as the lining of
the bladder have essentially the same structure: a basal labyrinth consisting of membranes and mito-
chondria, with the same structure as the basal areas of the intestinal cells. In freshwater fish, the extent
of the membranes and density of the mitochondria increase with the distance of the cells from the
glomeruli, with maximal development of the basal labyrinth occurring at the end of the collecting tubules
and in the bladder. In seawater fish, the basal labyrinth is less well developed and a gradient is usually
not noticeable (Wendelaar Bonga, 1973).
Toxicological studies have revealed extensive histopathological alterations in the kidney as a result of
exposure of fish to heavy metals and organic chemicals. In general, the structural damage to the kidneys
seems to show little toxicant specificity. The proximal tubules appear to be the first affected, but damage
progresses to the posterior segments and glomeruli, following exposure of the fish for a longer period
or to a higher concentration of the toxicant. Histopathological effects vary from slight disruption of the
brushborders of the proximal tubular cells, increased numbers of phagosomes and lysosomes, and
structurally abnormal mitochondria to rupture of cellular membranes, swelling and vacuolization,
increased cell death by necrosis and apoptosis, and large lesions in the tubular epithelia (Gill et al., 1989;
Oulmi and Braunbeck, 1996; Sovenyi and Szakolczay, 1993). Cadmium is well known for its preference
for renal tissue as a site of accumulation; the highest concentrations of this metal, after water as well
as dietary exposure, are usually found in the kidneys (Bentley, 1991; McCoy et al., 1995; Thomann et
al., 1997). As a consequence, cadmium is able to produce severe histopathological alterations (Gill et
al., 1989; Ooi and Law, 1989; Oronsaye, 1989; Sovenyi and Szakolczay, 1993). Although copper has
no specific affinity for the kidneys, it can also produce significant structural damage to both glomeruli
and renal tubules (Bakshi, 1991). Among the many organic chemicals producing similar effects are
paraquat (Molck and Fries, 1997), 4-chloroaniline (Oulmi and Braunbeck, 1996), TCDD (Henry et al.,
1997), cyclosporin (Terrero and Coombs, 1989), and atrazine (Fischer-Scherl et al., 1991).
Given the severity of the histopathological changes it is clear that renal functions, including hydrom-
ineral regulation of the kidneys, will be affected with a severity depending on the concentration and
length of exposure. Among the relatively few studies dealing with renal functions are reports on the
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inhibitory effects of silver on K -dependent p-nitrophenol phosphatase (Bury, 2005) and of cadmium,
chromium (Venugopal and Reddy, 1993), copper, and mercury (Lan et al., 1993) on renal tubular
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Na /K -ATPase, Ca -ATPase, and Na /Ca exchange activity. The mechanisms of action may be similar
as described for the gills and intestine: specific interactions with the ion-transporting molecules at lower
concentrations and lethal cell damage at higher concentrations via induction of cellular necrosis or
apoptosis. The latter, less specific way of reduction of renal ion transport activity may be typical of most
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organic pollutants. The reduction of Na /K -ATPase activity induced by paraquat has been related to the
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disruption of this chemical on mitochondrial electron chain transfer, which results in reduction of
metabolic functions (Molck and Fries, 1997). The nephrotoxicity of cyclosporin is based primarily on
its action as a calmodulin inhibitor, and its effects on renal hydromineral regulation have been ascribed
to interference with calmodulin-dependent ion transport mechanisms (Terrero and Coombs, 1989).
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An interesting finding on copper was the decreased renal Na efflux of freshwater rainbow trout
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following exposure to waterborne copper. Given the strong inhibitory action of copper on Na /K -ATPase