Glomerular therapeutics: looking back, looking forward.

Abstract

Fifty years ago, the prospects for treatment of glomerulonephritis were dim. Beginning around 1950 the field of "glomerular therapeutics" was begun by the introduction of new agents (adrenocorticotrophic hormone, cortisone, nitrogen mustard) as possible disease-modifying therapies for the various forms of glomerular disease. For the next several decades these and other agents (azathioprine, cyclophosphamide, chlorambucil, prednisone) were used therapeutically in a largely uncontrolled and anecdotal fashion. The application of randomized, controlled trials led to the adoption of some forms of therapy as both effective and reasonably safe, and the rejection of others as either ineffective or hazardous. New regimens involving different routes of administration or dosing schedules were adopted. After about another two decades, new and increasingly selective agents began to be introduced into the therapeutic armamentarium (cyclosporine, mycophenolate mofetil). Diseases previously associated with a very poor outcome were transformed into manageable disorders. The consequences of glomerular disease (e.g., nephrotic syndrome, chronic renal failure) were now subject to control and alleviation in many circumstances. The next transformation of "glomerular therapeutics" is now under way. The revolution in molecular genetics and pharmacogenomics will allow new agents to be developed that target specific aspects of the pathogenic mechanisms underlying glomerular disease. This transformation will not be an easy one, because development, testing, approval, and application of these new concepts in therapeutics (e.g., somatic gene therapy) will be time consuming and expensive. Eventually, the understanding of the genetic basis of susceptibility to glomerular disease and its progression will allow a preventative and curative, rather than palliative, strategy to emerge.