Abstract. Medullary and glomerular amyloidosis, papillary necrosis, and secondary interstitial disease were diagnosed in eight related adult Abyssinian cats from two catteries. The lesions were similar to those in two unrelated mongrel cats with renal amyloidosis. Ultrastructurally, the patterns of amyloid deposition were as described in other species, although medullary deposition predominated. Potassium permanganate oxidation blocked Congo red staining of the deposits suggesting that they contained amyloid A protein (secondary amyloid). The disease may be a model of familial secondary amyloidosis and offers an opportunity to study the pathogenesis of both amyloid deposition and papillary necrosis.The histochemical characteristics of feline renal amyloid require careful attention to technique. Section thickness affects Congo red affinity and both dichroism as well as birefringence should be considered when interpreting staining reactions. Thioflavine-T may be the preferred stain for identification of small deposits of amyloid. Variation in section thickness markedly affected the degree of potassium permanganate oxidation.

Spontaneous renal disease in the pigtailed macaque was evaluated in a prospective study of 20 apparently healthy monkeys that were killed and a retrospective study of 674 monkeys that died of spontaneous disease. Many apparently normal pigtailed macaques have a mesangioproliferative glomerulonephritis of slight to moderate severity. Deposition of immunoglobulin, particularly IgM, was common in renal glomeruli and did not seem to correlate with renal disease. Glomerulonephritis was found in 14% of the adult monkeys that died of spontaneous disease; in 4.2% it was severe enough to have caused renal failure. Tubular nephrosis was the most common renal lesion (22.6% of adults) and was usually a nephrotoxicity resulting from treatment of diarrhea with nephrotoxic antibiotics. Other lesions found were incidental or were secondary to disease processes in other organs. Pigtailed macaques that have been in our colony at least six months have a higher incidence of renal disease than is reported elsewhere in Old World monkeys.

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In certain cases, quantitative tissue structural data derived from tissue sections may be required to make critical decisions in the drug development or risk assessment process. Most frequently, these questions center on test article-related effects on cell number. In this opinion article, the limitations of estimating cell number by standard cell or nuclear profile counts from sections/blocks collected for routine histopathology are discussed from both a scientific and regulatory perspective and contrasted with the robust, sensitive, statistically based methods of design-based stereology. Specific existing industry practices are reviewed. Recent advances in stereological theory, software, hardware, and automated immunohistochemical staining now make it feasible to implement unbiased stereological methods to assess test article-related effects on cell number in a regulatory toxicology setting. These design-based stereological methods for counting cells are recommended when the quantification of small changes in cell number is critical to the risk assessment or decision-making process. These methods provide levels of sensitivity and statistical guarantees of accuracy that no other currently available tissue section-based methodology can provide.

Mesangioproliferative glomerulonephritis was found in 28 of 113 pigtailed macaques (Macaca nemestrina) that died in 1977. In five it was considered severe enough to cause significant renal dysfunction; in two of these it was the cause of death. The basic lesion was a proliferation of mesangial cells and deposition of mesangial matrix in the mesangial stalk, resulting in various degrees of stalk expansion and increased lobulation of the glomerular tuft. Preliminary immunofluorescence and ultrastructural studies suggests the pathogenesis of the lesion may involve deposition of antigen-IgM immune complexes in the mesangial region.