Association between VEGF receptors and baseline peritoneal transport status in new peritoneal dialysis patients

Peritoneal transport status is important not only for prescription, but also as a prognostic index. Flt-1 and Flk-1, the major vascular endothelial growth factor receptors involved in angiogenesis and hyperpermeability, may play a potent role in determining peritoneal transport characteristics. However, the relationship between them has not been studied to date. We hypothesized that Flt-1 and Flk-1 expression in the peritoneal vasculature of uremic patients could be closely related to baseline peritoneal transport status.

Thirty-six new patients without a previous history of peritonitis were enrolled. Clinical parameters such as age, sex, height, weight, causes of renal failure, and residual renal function were assessed. Parietal peritoneal biopsies were obtained during implantation of peritoneal dialytic catheters. Flt-1 and Flk-1 were semi-quantitatively evaluated by immunohistochemical staining. Peritoneal microvascular density (MVD) was counted. Within 6 weeks after commencing peritoneal dialysis, a standard peritoneal equilibration test was performed, and the dialysate-to-plasma concentration ratio for creatinine at 4 h (D4/P Cr) was determined. The patients were divided into two groups based on the D4/P Cr: more than 0.65 (Group H, n = 22) and less than or equal to 0.65 (Group L, n = 14). The 24-h peritoneal protein excretion (PPE) was assayed. Flt-1 and Flk-1 were correlated with peritoneal MVD, D4/P Cr, and PPE.

Flt-1 and Flk-1 were detected in the peritoneal vasculature of uremic patients. Flt-1 expression was similar between the two groups, but Flk-1 expression in Group H was significantly higher than that in Group L (p = 0.001). Flt-1 expression did not show significant correlations with peritoneal MVD, D4/P Cr, and PPE. However, Flk-1 expression showed significant correlations with the above three parameters (p < 0.001 for all).

For the first time, the expressions of Flt-1 and Flk-1 in peritoneal vasculature of uremic patients were detected. Flk-1 expression in peritoneal vasculature of uremic patients is closely correlated with the number of peritoneal microvessels, peritoneal small solute transport rate, and PPE. Our findings strongly suggest that Flk-1 may be a crucial determinant of baseline peritoneal transport characteristics. Further interventional studies are needed.