Implication of Peritubular Capillary Loss and Altered Expression of Vascular Endothelial Growth Factor in IgA Nephropathy

Abstract

BACKGROUND/AIMS: To determine the roles of peritubular capillary (PTC) loss and expression of vascular endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1 (HIF-1), in the progression of IgA nephropathy (IgAN), we analyzed the expression of VEGF and HIF-1, and the number of PTCs in patients with variable severity of IgAN. METHODS: Renal biopsy specimens from patients with IgAN (n = 23) were classified according to interstitial injury score: grade 0 (0%), grade 1 (1-25%), grade 2 (25-50%) and grade 3 (50-100%). We examined the immunohistochemical expression of CD34, VEGF and HIF-1alpha. RESULTS: VEGF was expressed in the cytoplasm of tubular epithelia, and VEGF-positive area significantly expanded in grades 1 (35.5 +/- 5.9%, mean +/- SD) and 2 (32.5 +/- 5.9%) compared with grade 0 (23.4 +/- 4.5%). The numbers of PTCs were significantly lower in grades 2 (559 +/- 49/mm2) and 3 (510 +/- 56/mm2) than grade 0 (708 +/- 49/mm2). HIF-1alpha was weakly expressed in tubular epithelia in grade 0, increased with progression to grade 2, and markedly decreased in grade 3. It was also increased in pericapsular interstitial area in grade 1. The expression pattern of HIF-1alpha did not parallel that of VEGF. In renal biopsies of 5 control patients with minor glomerular abnormality, glomerular expression levels of VEGF and HIF-1alpha were similar to those of IgAN grade 0 kidneys. CONCLUSION: VEGF production was accelerated in the early stage of IgAN but it did not protect against PTC injury/loss. The lack of correlation between VEGF and HIF-1alpha expression suggests HIF-independent VEGF production in IgAN.