In the majority of AAV patients, no immune complex deposits were found in their renal biopsies. C3d, C4d and C5b-9 staining, however, was found to be positive in a majority of analysed renal biopsies. Importantly, C3d and properdin staining was associated with cellular crescents. We hypothesize that local immune complexes are quickly degraded in AAV and therefore not visible by electron microscopy. Our findings are compatible with the hypothesis that complement activation in AAV occurs predominantly via alternative pathway activation.

Thin-basement-membrane nephropathy, also called benign recurrent hematuria, is characterized by diffuse thinning of the glomerular basement membrane and by hematuria. To determine the incidence of thin-basement-membrane nephropathy among patients with idiopathic hematuria, we conducted a prospective study in the nephrology units of three large hospitals in the Netherlands. Eighty normotensive adults without azotemia underwent renal biopsy because of recurrent macroscopic hematuria (n = 26) or persistent microscopic hematuria (n = 54). Idiopathic IgA nephropathy was found in 27 of the 80 patients. Light microscopical examination showed that 42 patients had normal renal tissue. The remaining 11 patients had mesangioproliferative glomerulonephritis (n = 5), interstitial nephritis (n = 3), or focal global glomerulosclerosis (n = 3). Tissue from the 42 patients whose renal biopsy specimens were normal when examined with light microscopy was analyzed morphometrically with electron microscopy to determine the thickness of the glomerular basement membrane. Two subsets of patients were identified by this analysis. In 18, thin-basement-membrane nephropathy was found (mean basement-membrane thickness [+/- SE], 191 +/- 28 nm; normal, 350 +/- 43 nm); all but one of these 18 patients had microscopic hematuria, which persisted during follow-up (median duration, 50 months). (Of the 54 patients who presented with microscopic hematuria, 17 [31 percent] had thin-basement-membrane nephropathy.) The thickness of the glomerular basement membrane was normal in the other 24 patients (361 +/- 69 nm); during follow-up, hematuria disappeared in all 13 of these patients who had macroscopic hematuria, and hematuria resolved in 5 of the 11 patients who had microscopic hematuria. We conclude that in patients with persistent microscopic hematuria, the incidence of thin-basement-membrane nephropathy is similar to that of idiopathic IgA nephropathy. Morphometric analysis of the thickness of the glomerular basement membrane should be included in the workup of adults with persistent microscopic hematuria that is not of urologic origin.

These results support the notion that TBMN is a disease of genetic heterogeneity; it is not a benign renal condition in a substantial number of patients, particularly those in late middle age.

In this study incidence rates of idiopathic glomerular disease in 1.5 X 10(6) Dutch adults between 16 and 65 years of age were determined, as well as the prevalence of these diseases in terms of indication for renal biopsy. The study was conducted between 1978 and 1985; indications for renal biopsy in decreasing hierarchical order were recently discovered uremia, nephrotic syndrome, chronic hematuria of less than two years duration with or without proteinuria or disturbed renal function, and chronic proteinuria of less than two years duration, of unknown origin. The main findings are fourfold. The incidence of IgA nephropathy and thin glomerular basal membrane lesions was high, 19 and 13 per 10(6) adults respectively, and the prevalence in patients biopsied because of non-azotemic chronic hematuria was 31% and 22%, respectively. In the normotensive non-azotemic adults biopsied because of chronic, mild proteinuria the prevalence of focal segmental glomerular sclerosis and vascular hyalinosis was both 41%. Of the patients biopsied because of nephrotic syndrome the prevalence of membranoproliferative glomerulonephritis (5%) was low, as was the incidence (less than 2 per 10(6) adults per year). Finally, the prevalence of diffuse sclerosing glomerulonephritis was 25% in patients biopsied because of uremia. This study is useful for the differential diagnosis of idiopathic glomerular disease.