Glomerulopathies of neoplasia

Abstract

The glomerulopathies occurring in neoplastic diseases may represent, particularly in patients with carcinoma, a manifestation of host response to the presence of tumor antigens which may be recognized as 'foreign' by the immune system. Evidence has been reviewed which supports the concept that immune deposits in the glomerulus represent aggregates of tumor-associated antigen-antibody complexes. These immunopathologic findings are compatible with existing data demonstrating that soluble circulating immune complexes are frequently present early in the course of a malignancy. This review of the existing literature would suggest that proteinuria is an early clinical manifestation of this immune phenomenon in occult carcinoma. The prognosis of patients with nephrotic syndrome due to neoplasia appears to be grave. While the number of patients with a given histologic diagnosis is too small for statistical analysis, a median survival of 3 mth after the first clinical manifestation of a tumor in 34 patients is impressively short. Perhaps the host response to tumor is responsible for this poor prognosis. Immune complexes have been detected bound to the surface of tumor cells, where they may interfere with lymphocyte-mediated hypersensitivity reactions against the tumor. In addition, circulating immune complexes may serve as 'blocking factors', having the capacity to modulate the immune response by interaction with sensitized lymphocytes, suppressing the cytotoxic potential of these cells. Paradoxically, the host immune response to the 'foreign' tumor cells may explain the poor prognosis seen in patients who develop immune complex glomerulopathy. The glomerulopathy of Hodgkin's disease and some other lymphoproliferative disorders is usually minimal change glomerulopathy, a pathologic entity of unknown pathogenesis. It has been postulated that the glomerular damage may be the result of a humoral principle derived from neoplastic cells or interacting lymphocytes. Certainly tumor cells can produce proteases which could conceivably be damaging to some element in the glomerular capillary wall. Despite these speculations, the cause of the lesion remains obscure. It appears that the activity of the glomerular lesion in these Hodgkin's disease patients correlates closely with the activity of the tumor. The nephrotic syndrome often appears at the time of the diagnosis of the tumor. Regression is observed with effective anti-tumor therapy, even when this therapy is confined to local irradiation. In some cases, subsequent exacerbations and remissions of the tumor have been associated with parallel changes in proteinuria. In contrast to the experience with carcinomas, there has been no indication that Hodgkin's disease patients who develop glomerulopathy have a poorer prognosis than other patients with this neoplasm (28 references).