Influence of Casein and Other Agents on the Production of Renal Lesions in Rats by Sulfadiazine and Acetylsulfadiazine

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Abstract
Sulfadiazine (1%) in a purified diet of low casein content (10%) fed to rats for 30 days has resulted in the uniform production of severe renal lesions. Casein, urea, NaHC03 and NaCl have been found to exert preventive actions on the development of these renal lesions, despite restriction of water intake. NaHCO3 was the most effective of these agents. The blood sulfadiazine concn. has been reduced by each of the preventive agents mentioned. The-magnitude of the blood sulfadiazine concn. may influence the production of these renal lesions, but there appear to be other significant factors as well. In expts. with NaHCO3, severe renal lesions have been prevented, even when high blood sulfadiazine concns. resulted from the feeding of a 4% sulfadiazine-containing diet. Increased conjugation of sulfadiazine and high renal concn. of conjugated sulfadiazine have been noted to be invariably associated with these severe lesions and have never been noted when lesions were prevented. Acetylsulfadiazine, despite its greater solubility and lower blood concn. than free sulfadiazine, was far more toxic than free sulfadiazine as judged by the incidence and severity of renal lesions and by survival.