Fibrogenic growth factors in encapsulating peritoneal sclerosis

Increased local levels of fibrogenic growth hormones contribute substantially to the process of encapsulating peritoneal sclerosis (EPS) in animal models.

We analyzed probes from patients with normal kidney function (n = 10), with normal kidney function and inflammation (n = 10), on PD without (n = 10) and with EPS (n = 9). We investigated the degree of fibrosis and the number of vessels and vasculopathy. Additionally, we investigated the expression of NFkappaB, TGFbeta1, TGFbeta1 receptor, TGFbeta2, TGFbeta2 receptor, FGF-BP, CTGF and VEGF by immunohistochemistry.

In EPS, we found an exclusive upregulation of VEGF (normal 0, appendicitis 1.0 +/- 1.2, PD 1.7 +/- 1.8 and EPS 5.7 +/- 4.4; p < 0.0001), whereas in PD, CTGF was significantly increased (normal 6.0 +/- 2.8, appendicitis 7.3 +/- 2.5, PD 10.0 +/- 1.8 and EPS 7.3 +/- 2.1; p = 0.0059). The results for the TGFbeta system and NFkappaB were not uniform, in EPS no increases were demonstrable. Vasculopathy was significantly more pronounced in EPS (normal 0.4 +/- 0.5, appendicitis 0.2 +/- 0.3, PD 1.0 +/- 0.7 and EPS 1.6 +/- 1.2; p < 0.0001) than in PD or inflammation (normal 30 +/- 16, appendicitis 82 +/- 48, PD 1,936 +/- 952 and EPS 2,613 +/- 1,209; p < 0.0001), whereas the density of vessels were decreased (normal 125 +/- 114, appendicitis 817 +/- 347, PD 81 +/- 57 and EPS 36 +/- 33; p < 0.0001).

The process of EPS was associated with increased VEGF in the peritoneum. The reduced density of vessels compared with marked fibrosis could point to hypoxia as an inducer.