Recent concepts in the pathogenesis and therapy of IgA nephritis

In IgA nephritis (IgA Nx) there is a general defect in clearance of immune complexes. IgA molecules are poorly solubilised by the complement system and allows its deposition in the kidney. In patients with IgA Nx there is a defect both in the sera and in the renal tissue. Lack of genetically mediated mesangial reactivity towards IgA Nx prevents clinical and histological manifestations of IgA Nx. Binding of IgA deposits to mesangial cells causes secretion of cytokines associated with a decrease in prostaglandin E2 synthesis and increases in thromboxane A2 production which promotes mesangial cell proliferation. Angiotensin II induces mesangial cell contraction and efferent arteriovasoconstriction. Any form of therapy for IgA Nx must be rational and practical. To limit amounts of mesangial deposits one may attempt to reduce antigen load, down-regulate lymphokines and employ enzymes to remove glomerular immune deposits. The Department's guidelines for therapy of IgA Nx consist of control of systemic hypertension, use of angiotensin II converting enzyme inhibitor for glomerular hyperfiltration, dipyridamole and low-dose warfarin, a low protein diet and control of serum cholesterol to prevent lipid-induced glomerulosclerosis. Future therapeutic strategies may include inhibition of mediators and cytokines (platelet-derived growth factor antagonists and tumour necrosis factor inhibitors) and gene therapy.