Pathogenesis and approaches to therapy of membranoproliferative glomerulonephritis.

In 1965, it was observed that patients with glomerulonephritis with persistently low serum concentrations of C3 evolved to have similar glomerular morphologic characteristics, particularly recognizable in biopsy specimens stained by the Jones methenamine silver technique [1]. Subsequent observations have indicated that although long-standing hypocomplementemia is commonly observed and is unique in patients with these glomerular morphologic characteristics, reduced C3 concentrations are not always present [2, 3] and the distinctive morphology is now the criterion for identification of the disease. Thus, the name first given, hypocomplementemic persistent (chronic) glomerulonephritis [1], is no longer appropriate and the descriptive terms membranoproliferative and mesangiocapillary glomerulonephritis have subsequently been applied. With time, electron microscopy of the glomerular lesion has shown that, based on the location of the glomerular deposits, patients with membranoproliferative morphologic characteristics fall into two groups. In about two-thirds of the patients [4], the deposits are present in the mesangium and in the subendothelial space. The basement membrane is normal. This form has been designated type I membranoproliferative glomerulonephritis (MPGN). In the remainder of the patients, deposits are present within the glomerular basement membrane as well as within the mesangium; subendothelial deposits are scanty or absent. This form, designated type II MPGN, or intramembranous dense deposit disease, was first recognized independently in 1963 [5]. In this form, dense deposits are also found in the basement membranes of Bowman's capsule and of the tubules. In addition, lobular glomerulonephritis is now recognized as a form of MPGN [4, 6, 7]. It should be noted that glomerular morphology closely resembling that of