Experimental Bence Jones cast nephropathy

Abstract

C3H mice received intraperitoneal injections of a single dose of 50 to 200 mg. of purified lambda Bence Jones protein. Control animals received injections of comparable amounts of ovalbumin. The mice which received 200 mg. of lambda Bence Jones protein developed extensive cast formation in the distal renal tubules. By electron microscopy, the casts were found to contain elongated crystalloid structures. In some areas, these crystalloids appeared to penetrate into or be engulfed by tubular epithelial cells. By immunofluorescence, only lambda Bence Jones protein was detectable in the casts during the first 5 days. Thereafter, Tamm-Horsfall protein was also found in increasing amounts. The casts induced an inflammatory response characterized by the sequential appearance of polymorphonuclear leukocytes and mononuclear cells. The secondary tubular cell changes included atrophy, degeneration, and regeneration. Giant cells were present around many casts, but it could not be determined whether these derived from tubular epithelial or mononuclear inflammatory cells. Elevated blood urea nitrogen was found terminally in most animals. Smaller doses of the same protein as well as preliminary studies with two other lambda Bence Jones proteins failed to produce comparable changes. This experimental model of Bence Jones nephropathy closely resembles the morphologic features of so-called "myeloma kidney" in man.