EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM : I. PREPARATION AND IMMUNOLOGICAL STUDIES OF NEPHROTOXIN

Abstract

Nephritis can be induced in rats by the injection of anti-kidney sera obtained from rabbits immunized with suspensions of perfused rat kidney. Anti-kidney sera, thus prepared, contain a number of antibodies capable, on injection into rats, of inducing a severe anaphylactoid reaction with general vascular manifestations that involve the kidney as well as other organs. These sera also contain a nephrotoxic agent that affects the kidney primarily. The nephrotoxic effect is characterized clinically by severe persistent albuminuria with casts, and transient anasarca during the acute disease, but no significant hematuria occurs. When a severe anaphylactoid reaction is superimposed on the nephrotoxic injury, hematuria is an outstanding feature. Nephrotoxin is demonstrable in vivo and is not related quantitatively to the precipitins in the anti-kidney serum against kidney extract. It is most readily obtained by immunization with kidney suspensions, but may occasionally appear after injections of other organ preparations; it does not result from immunization with erythrocytes or serum. Nephrotoxin is present in the globulin fraction of anti-kidney serum. The nephrotoxic action of anti-kidney serum is easily removed by absorption with kidney cells or fat-free kidney tissue. Similar preparations of liver likewise remove it, but less readily. Neither kidney, liver, or brain lipids affect it, nor does absorption with red blood cells or serum. Nephrotoxin appears to be an antibody that is relatively organ specific in its affinities. It differs from the more common antibodies involved in reverse anaphylaxis in one respect, at least: The animal rapidly becomes desensitized against the latter and fails to react, whereas desensitization to nephrotoxin is difficult to secure.