Page 298 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Renal Toxicity Chapter | 16 265

VetBooks.ir TABLE 16.1 (Continued) Species Lesion Comment

Toxicant
Zinc All Tubular degeneration and necrosis;
hemoglobinuric nephrosis
Distal Tubular/Collecting Duct Injury
Fluoride All Distal tubular degeneration and
necrosis
Melamine:cyanuric acid Dogs, cats, Distal tubular degeneration and See text for more information
raccoon dogs, necrosis; crystals in distal tubules
pigs, rats, fish; and collecting ducts
others likely
susceptible
Interstitial Injury
Vicia spp. (vetch) Grazing animals, Eosinophilic granulomatous Lesions can occur in any organ
primarily cattle nephritis
Lower Urinary Tract Injury
Cyclophosphamide Dogs Hemorrhage and necrosis of urinary Bioactivation and concentration
bladder of toxic metabolites in urine
Ptaquiloside (Pteridium spp., Cattle Necrosis and hemorrhage of urinary Enzootic hematuria
bracken fern) bladder; urinary bladder neoplasia
Ptaquiloside (Sorghum spp.) Horses Necrosis and hemorrhage of urinary Equine cystitis ataxia syndrome
bladder

a
Sonne-Hansen C, Dietz R, Lieffson PS, et al. (2002) Cadmium toxicity to ringed seals (Phocahispida): an epidemiological study of possible cadmium-
induced nephropathy and osteodystrophy in ringed seals (Phocahispida) from Qaanaaq in Northwest Greenland. Sci Total Environ 295: 167 181.
b
Haschek WM, Rousseaux CG, Wallig MA (2007) Kidney and lower urinary tract. In Fundamentals of Toxicologic Pathology, second ed. Academic Press,
San Diego, pp. 221 238.
c Boorman GA, McDonald MR, Imoto S, Persing R (1992) Renal lesions induced by ochratoxin A exposure in the F344 rat. Toxicol Pathol 20: 236 245.
d Brown TP, Fletcher OJ, Osuna O, Wyatt RD (1987) Microscopic and ultrastructural renal pathology of oosporein-induced toxicosis in broiler chicks. Avian
Dis31: 868 877.

Glomerular Injury Proximal Tubular Injury
The glomerular capillaries are the first component of the Tubular injury is the most common pattern of renal injury
nephron to be exposed to blood-borne toxicants. The glo- induced by toxicants and the proximal tubule is most fre-
merular cells, matrix and mesangium are susceptible to quently affected by nephrotoxicants (Schnellmann, 2008).
toxic injury by several different mechanisms including Damage to the proximal tubule may occur from direct dam-
direct injury to cellular components, formation of oxygen- age from toxicants, metabolic activation of toxicants,
derived free radicals, disruption of extracellular substrates ischemia-reperfusion, or physical or chemical disruption of
(e.g., basement membranes), immune-mediated injury and endothelium and/or basement membrane. The S 1 segment is
disruption of renal hemodynamics (Khan and Alden, the most vulnerable to injury from toxicants that exert direct
2002). Direct injury or injury secondary to reactive oxy- injury as the epithelium in this area is exposed to the toxi-
gen intermediates can result in endothelial loss, glomeru- cant first. The proximal convoluted tubule epithelium is
lar podocyte injury and necrosis of mesangial cells and actively involved in endocytosis of various compounds that
substrate (mesangiolysis). Further damage may occur sec- bind to the brush border, sequestering the compounds in
ondary to cytokines released by inflammatory cells phagolysosomes. When this process is overwhelmed by the
responding to the site of injury. Alterations in the GBM presence of certain toxicants (e.g., aminoglycoside antibio-
subsequent to cellular injury can result in disruption of tics), loss of phagolysosome membrane integrity occurs,
the glomerular filtration barrier, leading to proteinuria. resulting in lysosomal leakage and cell injury or necrosis
Deposition of toxicant-immune complexes and immune- (Khan and Alden, 2002). This type of injury is most com-
mediated reactions to various toxicants (e.g., mercurial, monly associated with the S 1 and S 2 segments of the proxi-
gold salts) can result in thickening of the GBM, disrupting mal tubule. In contrast, the straight segment (S 3 )ismost
the glomerular filtration barrier and leading to membra- susceptible to injury by metabolic activation, transporter-
nous glomerulonephropathy. associated accumulation, and reperfusion injury.