The Molecular Pathogenesis and Experimental Therapy of IgA Nephropathy  Recent Advances and Future Directions.

Hsu   I-Hong   Stephen

doi:10.2174/1566524013363852

Abstract

In 1968 Berger and Hinglais published the first description of IgA nephropathy (IgAN). In the ensuing 30 years, extensive clinical, epidemiologic, and immunologic characterizations of primary (idiopathic) glomerulonephritis with IgA as the predominant or co-dominant immunoglobulin deposited in the mesangia of all glomeruli, have established the features of IgAN as a distinct glomerular disease entity. Despite these efforts, the basic molecular mechanism(s) which mediate abnormal mesangial IgA deposition with ensuing extracellular matrix expansion and mesangial cell proliferation remains poorly understood, definitive diagnosis still depends on histologic examination of renal biopsy specimens, and widely accepted standards for effective therapy remain to be defined. This review will begin with a summary of the earlier descriptive histopathologic and clinical epidemiologic work which firmly established the distinct immunohistologic features of IgAN, the most common glomerulonephritis among patients undergoing renal biopsy and a major cause of renal failure worldwide. In recent years, a series of important advances in the areas of molecular pathogenesis and experimental therapy have emerged, reflected in a molecular paradigm shift in the techniques and approaches applied to the study of IgAN. Representative studies will be critically evaluated to highlight both the strengths and potential weaknesses of each of these approaches. Throughout, the author will offer a personal perspective on promising areas of new investigation and potential approaches to the identification of disease susceptibility genes involved in the development and progression of IgAN, the application of these discoveries through the development of clinically useful molecular diagnostic tests, and the rational design of novel therapeutic strategies.

Keywords: Molecular Pathogenesis, IgA Nephropathy, Complement Activation, IgA-Fibronectin, Intraglomerular Coagulation, Inhibitors of Complement Activation, Inhibitors of Angiotensin II Activity, Antioxidant Therapy, Inhibitors of Coagulation