Proximal tubular epithelial hyperplasia in patients with chronic glomerular proteinuria

Background Proteinuria is known to affect the proximal tubular epithelial s tructure and function. The present study tested the hypothesis that chronic proteinuria leads to hyperplasia of proximal tubular epithelium. Methods. This hypothesis was tested by morphometric analysis of the renal b iopsy specimens in two groups of patients. Group A (N = 15) was composed of patients with chronic glomerular proteinuria who, for clinical indications , underwent renal biopsy of their native kidneys on two separate occasions. The proteinuria was sustained during the first and second renal biopsies i n all but two of the patients with minimal change nephrotic syndrome who ex perienced transient remission. Group B (N = 10) was composed of patients wi th little or no proteinuria who underwent renal biopsy because of unexplain ed hematuria and whose renal biopsy showed only thin glomerular basement me mbrane (GBM) disease. Results. In Group A, the mean number of epithelial cell nuclei per proximal tubule cross-section increased significantly from the first to the second renal biopsy (11.0 +/- 2.7 vs. 13.0 +/- 2.2, P = 0.005, paired t-test). Als o, those with severe proteinuria showed proximal tubules with reactive epit helium (large pale nuclei with a high nucleus to cytoplasm ratio) and marke d hyperplasia (double and triple layers of epithelium). Such changes were n ot seen in group B renal biopsies. Compared with group A biopsies, group B biopsies showed a lower mean value for proximal tubular epithelial cell nuc lei per tubular cross-section (P = 0.056) and a higher mean proximal tubula r volume (P = 0.049). As a consequence, the mean number of nuclei per relat ive tubular volume was significantly greater in group A compared with group B (0.55 +/- 0.14 vs. 0.40 +/- 0.06, P = 0.003, by Wilcoxon rank sum). Conclusions. Chronic heavy proteinuria is associated with hyperplasia of pr oximal tubular epithelium and contraction of proximal tubular volume. These events may impair glomerular filtration and represent another mechanism of progression of renal disease.