IgA Nephropathy

Abstract

Mmunoglobulin A nephropathy (IgAN) is defined by the predominant deposition of IgA in the glomerular mesan- gium. Light microscopic appearances and clinical features can vary considerably, reflecting the many patterns of histopatho- logic injury seen in this glomerulonephritis (GN) Closely associ- ated with IgAN is Henoch-Schonlein purpura (HSP), a small- vessel systemic vasculitis characterized by small blood vessel deposition of IgA predominantly affecting the skin, joints, gut, and kidney. The nephritis of HSP is also characterized by mesan- gial IgA deposition and may be histologically indistinguishable from IgAN. Both clinical and laboratory evidence support a close relationship between IgAN and the nephritis of HSP (1). This article focuses on IgAN considering especially new information available since IgAN was last reviewed in the Journal of the Amer- ican Society of Nephrology (2). In particular, we focus on our grow- ing understanding of the pathogenesis of IgAN, and we discuss the impact of recently published randomized, controlled trials (RCT) on recommended treatment strategies. Epidemiology and Clinical Features The clinical course of IgAN is well established and has re- cently been reviewed elsewhere (3). There are a number of clinical features for which there is no certain explanation; these include the male preponderance, the apparent peak incidence in the second and third decades of life, the very wide range of presenting clinical features, and the variable tempo of disease after diagnosis. Data from Japan suggest that the prevalence of subclinical "lanthanic" IgAN may be even higher than already suspected, on the basis of renal biopsies in living kidney do- nors, in which 16% were found to have previously unknown mesangial IgA (4). The geographic differences in apparent prevalence of IgAN—higher in the Pacific Rim, where inci- dence in older patients is reported to be increasing, and South- ern Europe, as opposed to northern Europe and North Amer- ica—are still the subject of debate. Varying approaches to the use of renal biopsy in patients with mild urinary abnormalities are often cited as one explanation, but worldwide practice is becoming increasingly uniform, and fewer nephrologists now recommend renal biopsy for people with asymptomatic micro- scopic hematuria in the absence of sustained proteinuria. Most prevalence data are generated from centers in major industri- alized cities in which the lifestyle is becoming increasingly uniform, suggesting that the varied incidence more likely rep- resents true differences among racial groups, rather than envi- ronmental in origin. However, genetic studies have so far been unrewarding in defining the pathogenesis of IgAN. The diagnosis of IgAN always requires renal biopsy. No clinical presentation is pathognomonic, not even the archetypal young male patient with episodic macroscopic hematuria after an upper respiratory tract infection, which is the presenting feature in 30 to 40% of cases. Most patients have only a few episodes of frank hematuria, and such episodes usually recur for a few years at