Ciglitazone, a new hypoglycemic agent. 5. Effect on renal lesions in C57BL/KsJ-db/db mice.

Kidneys of treated and control C57BL/KsJ-db/db mice were analyzed by semiquantitative light microscopy to determine the effects of ciglitazone on the deposition of fluorescein-conjugated IgM and IgG and of PAS-positive material in the glomerular mesangium and renal tubules. Long-term administration (12 and 20 weeks) of ciglitazone significantly improved the blood glucose of most of the treated db/db mice. There appeared to be a reduction of glomerular IgM and IgG in the treated compared with the control group, although IgM did not achieve statistical significance due to heavy stain deposition in two of the treated mice with continuous and severe hyperglycemia. Treated and control mice displayed a similar diffuse expansion and mild thickening of the glomerular mesangium characterized by moderate deposition of PAS-positive material. Expansion of the mesangium was probably not retarded or prevented by ciglitazone therapy since this pathologic process may be controlled by an interaction of metabolic factors other than hyperglycemia per se in the db/db mouse. Glycogen vacuolization (Armeni-Epstein lesion) of the renal tubules was completely ameliorated in the treated mice which showed a reduction of hyperglycemia. The results of this study suggest that prolonged treatment with ciglitazone elicits an improvement of hyperglycemia which seems to retard or reverse glomerular immunopathology and completely reverse tubular derangement but does not prevent expansion of the glomerular matrix in severely diabetic C57BL/KsJ-db/db mice.