Contribution of immunological reactions to nephrotoxicity

Several toxic agents, such as mercurials and agents with a sulphydryl group (e.g., gold salts, D-penicillamine and captopril), are associated with the occurrence of membranous glomerulopathy. DR3 antigen-positive subjects and poor sulphoxidators are at higher risk than other patients when treated with gold salts or D-penicillamine. Other drugs, mainly nonsteroidal anti-inflammatory agents and lithium salts, are responsible for the nephrotic syndrome with minimal glomerular changes, a T-cell-mediated disease. Several models of drug-induced membranous glomerulonephritis have been developed. These have been used to confirm the role of most of the above-mentioned agents and have made it possible to shed some light on the possible mechanisms involved. Mercurials induce a polyclonal activation of B cells in rats which is related to the appearance of autoreactive T cells. Finally, numerous agents may induce immunologically mediated acute interstitial nephritis. Although cell-mediated immunity appears to be involved in most cases, experimental models are lacking to substantiate this hypothesis.