OMEGA 3 FATTY ACIDS IN IGA NEPHROPATHY

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IgA nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a variable clinical course with progression to chronic renal disease in 20-40% of patients. Dietary fish oil supplementation significantly retarded the rate of renal function in a group of proteinuric patients with IgA nephropathy in a recently completed clinical trial conducted by the Mayo Nephrology Collaborative Study Group. Currently, it is difficult to identify patients that would be most likely to benefit from such therapy, because there are few clinicopathologic parameters that provide prognostic information in an individual patient. Since endocapillary proliferation and extracellular matrix deposition are principal morphologic alterations in IgA nephropathy, we propose to determine whether new methods to assess these parameters may provide additional prognostic information and provide a basis for therapeutic decisions in newly diagnosed patients. The role of glomerular and interstitial proliferation in predicting outcome in IgA nephropathy will be determined by immunostaining renal biopsies with MIB-1, which identifies an antigen expressed in G1, S2, S, and M phase cells, but not in G0 cells. Since TGFbeta is a dominant mediator of extracellular matrix production, deposition of this cicatricial mediator in renal biopsy material will be assessed by immunohistochemical staining. To clarify the role of collagen I and collagen IV accumulation during the course of progressive IgA nephropathy, deposition of these macromolecules will also be assessed by immunohistochemical staining. Diagnostic renal biopsies obtained from 106 patients with IgA nephropathy, the study cohort of the recently completed clinical trial, will be used to establish progression risk factors based upon glomerular and interstitial proliferation indices and relative expression of TGFbeta, collagen I, and collagen IV. Patients with IgA nephropathy and high progression risk factors will be entered into a prospective study to assess the effects of varying amounts of omega (n)-3) highly unsaturated fatty acids administrated in fish oil concentrates on renal function outcome.