Immunosuppressive Treatment in the Prevention of Renal Failure in Primary Glomerular Diseases

Abstract

The use of corticosteroids and cytotoxic agents, alone or in combination (“immunosuppressive therapy”), in the treatment of primary or idiopathic glomerular disease has a long and checkered history. Early uncontrolled therapeutic trials conducted without due regard for the natural history led to unwarranted enthusiasm regarding the efficacy of immunosuppressive agents in the therapy of the various clinico-pathologic entities grouped under the heading of primary glomerular disease. Beginning about a decade ago, prospective, randomized, controlled trials identified the clinical and morphologic characteristics of potentially responsive and unresponsive patient populations with primary glomerular disease. Thus, a more cautious and selective application of these agents emerged. Furthermore, these and other studies provided a fuller understanding of the potential hazards of long-term usage of immunosuppressive agents. Presently, only the primary glomerular disease in which nephrotic syndrome is accompanied by minimal glomerular alterations (“minimal change disease”) can be regarded as clearly responsive to either corticosteroids or cytotoxic agents. However, encouraging data has recently appeared suggesting a benefit of corticosteroids on the course of membranous nephropathy. Also, the relentlessly progressive course of primary crescentic glomerulonephritis may be beneficially altered by the aggressive use of immunosuppressive agents in combination with either anticoagulants or antithrombotic drugs or intensive plasma exchange, providing such therapy is begun in the early stages of the disease. Those primary glomerular diseases which are characterized by focal and segmental glomerular sclerosis, diffuse mesangial proliferation and membranoproliferative alterations, although quite common, have not as yet been unequivocably proven to be benefited by immunosup-pressive drugs, at least in terms of progression of renal failure. Encouraging preliminary data regarding the use of anticoagulants or antithrombotic agents, alone or in combination with immunosuppressive agents, will require further exploration. It is hoped that as the etiology, pathogenesis and natural history of the various categories of primary glomerular disease are better understood and long-term, randomized controlled trials of therapy are conducted in more homogeneous populations of patients, that subsets may be defined in which careful application of immunosuppressive agents may extend useful life with a minimum of adverse consequences. Such studies, although tedious and expensive, may lead to the avoidance of needless and hazardous therapy of an unresponsive population. Furthermore, if a responsive population can be defined, even if it is a minority of patients, the resulting extension of useful life free of the need for dialysis, even for a few years, may represent a substantial savings in health care dollars considering the high cost of maintenance dialysis or initial transplantation.