Background. Although there have been many reports on clinicopathological studies of IgAN, information is limited regarding the long-term evolution of a renal histology by analysing samples obtained not only during normal renal function but also after the establishment of an impaired renal function in individual patients. Methods. We analysed 18 pairs of serial biopsy specimens from 18 patients with IgA nephropathy (IgAN) in whom the first renal biopsies were performed while normal renal function was still present and the second biopsies were performed after impaired renal function was established. The glomerular density (GD, number of non-sclerotic glomeruli per renal cortical area) and mean glomerular area (MGA) were compared between the specimens. Results. The GD at the first biopsy of each patient showed a striking variation (1.3–5.2/mm2). As a whole, the GD decreased (2.7 ± 1.2 versus 1.4 ± 0.7/mm2) and the MGA increased (19.7 ± 4.2 × 103 versus 23.5 ± 4.5 × 103 mm2) between the biopsies, respectively. The degrees of change in the GD and the MGA between the biopsies differed remarkably among the individuals. The patients with a high GD in the first biopsy progressed slowly, but showed a large decrease in the GD and a large increase in the MGA between the biopsies, respectively. The patients with a low GD, who already had enlarged glomeruli in the first biopsy, tended to progress rapidly. Conclusions. Our results suggest that both the nephron number and glomerular enlargement play a crucial role as compensatory mechanisms against renal functional deterioration in progressive IgAN. The GD during normal renal function may determine these compensatory changes and thereby make it possible to predict the renal prognosis in IgAN. [ABSTRACT FROM AUTHOR]