Fibrogenic Growth Factors in Encapsulating Peritoneal Sclerosis

Abstract

Background: Increased local levels of fibrogenic growth hormones contribute substantially to the process of encapsulating peritoneal sclerosis (EPS) in animal models. Methods: 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 NFκB, TGFβ1, TGFβ1 receptor, TGFβ2, TGFβ2 receptor, FGF-BP, CTGF and VEGF by immunohistochemistry. Results: 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 TGFβ system and NFκB 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). Conclusions: 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.

Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients

“…Peritoneal biopsies of uremic patients before the start of PD were obtained during catheter insertion. All biopsies were formalin fixed and paraffin embedded following routine protocols (7,32). Patients with an episode of peritonitis within the last 6 mo were excluded.…”

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

“…studied the protein expression of TGFβ1, CCN2, and VEGF in the peritoneum of nine EPS patients who underwent surgery for bowel obstruction after a PD duration of 103±32 months [44]. For comparison, they studied patients on PD (n = 10, mean PD duration 19±28 months) and 10 non-renal surgical controls with normal peritoneum.…”

“…In view of the prominent overexpression of VEGF in EPS biopsies in our study and that of Braun et al . [44], it is disappointing that the longitudinally obtained dialysate VEGF concentration could not predict the development EPS in patients on PD [54], which makes it difficult to apply any preventive anti-VEGF therapy. Finally, TGFβ1 is also not a useful diagnostic marker for EPS as only an inactive soluble form is present in peritoneal effluent [55], [56].…”

Periostin: A Matricellular Protein Involved in Peritoneal Injury during Peritoneal Dialysis

“…Vascular endothelial growth factor A (VEGFA) has been shown to be important in that process (38,39). Tumors promote angiogenesis through the release of periostin (40).…”