International Journal of Nephrology Table 2: Eﬄuent markers and eﬄuent markers-to-eﬄuent cancer antigen 125 ratio in patients with high transport rate and others. Group n Eﬄuent HGF (pg/mL) Eﬄuent HGF/CA125 (pg/U) Eﬄuent BMP-7 (pg/mL) Eﬄuent BMP-7/CA125 (pg/U) Eﬄuent VEGF (pg/mL) Eﬄuent VEGF/CA125 (pg/U) Eﬄuent IL-6 (pg/mL) Eﬄuent IL-6/CA125 (pg/U) Eﬄuent CA125 (U/mL) Patients with high transport rate 14 240.0 (197.5–319.3)∗∗∗ Others 91 133.0 (107.0–216.0) 19.0 (10.8–33.2) 13.7 (8.0–25.9) 8.3 (7.4–9.4) 0.6 (0.5–0.8) 7.5 (4.8–9.1) 0.6 (0.3–1.2) 33.0 (29.0–34.0)∗∗ 25.0 (20.0–31.0) 2.5 (1.7–3.7) 2.3 (1.4–3.7) 23.8 (13.9–35.1)∗ 11.6 (6.7–24.0) 1.9 (1.3–2.2)∗ 13.3 (7.6–18.9) 1.1 (0.6–1.8) 11.1 (6.3–20.0) Data are medians with 25 and 75% interquartile ranges in parentheses. HGF: hepatocyte growth factor, BMP-7: bone morphogenic protein-7, VEGF: vascular endothelial growth factor, IL-6: interleukin-6, CA125: cancer antigen 125. ∗P < .05 compared with others, ∗∗P < .01 compared with others, ∗∗∗P < .001 compared with others. EMT of mesothelial cells is associated with high peri- toneal transport [17]. There is emerging evidence that the mesenchymal conversion of mesothelial cells is an important mechanism for the failure of peritoneal membrane function [18–20]. High levels of glucose, glucose degradation prod- ucts, a low-PD solution pH, inﬂammation, and angiotensin II are responsible for the production of transforming growth factor β (TGF-β) and VEGF, which induce EMT, by mesothelial cells [1]. TGF-β is a key regulator of EMT [1, 20]; however, the measurement of TGF-β is not easy because of its low concentration in dialysis eﬄuent ﬂuids [6]. In addition, it is not clear whether measuring the amount of TGF-β protein in peritoneal ﬂuid, in which it is mostly found in an inactive state, that is, bound to a latency-associated protein, is reﬂective of the tissue levels of active TGF-β [6, 21] and a previous study found no diﬀerences in TGF-β at any time in a comparison of patients treated with low-GDP solution and patients treated with high-GDP solutions [6]. VEGF was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis, and eﬄuent VEGF was found to be correlated with solute transport but not the TGF-β1 level [22, 23]. IL−6 is a cytokine involved in the acute-phase inﬂam- matory reaction, and dialysate IL-6 levels and VEGF con- centrations are associated with a high peritoneal solute transport rate [24]. It has also been reported that HGF 3 and BMP-7 ameliorate high-glucose-induced EMT in the peritoneal mesothelium [4]. Furthermore, it was reported that measuring the dialysate VEGF, level relative to the eﬄuent CA125 level revealed a signiﬁcant association with EMT, whereas unadjusted levels of the growth factor did not [6]. Thus, we studied the relationship between peritoneal transport characteristics and eﬄuent HGF, BMP-7, VEGF and IL-6 levels and their values relative to the eﬄuent CA125 concentration, focusing on EMT in patients being treated with PD using new, biocompatible PD solutions. Consistent with previous reports, VEGF and IL-6 levels were signiﬁcantly diﬀerent between patients with high transport rate and others [24]; however, eﬄuent HGF levels showed bigger diﬀerence in these two groups in our study. We considered that using a low-GDP, neutral-pH, dual- chamber bag PD solution also causes EMT since high glucose itself induces EMT in cultured human peritoneal mesothelial cells [4]. According to previous studies, it is conceivable that the mesothelial cells of patients with high transport rate undergo EMT and display decreased production of HGF and BMP-7. However, in our study, the high transport rate group showed increased eﬄuent HGF concentrations. HGF is a heterodimeric molecule composed of a 69 kDa alpha subunit and a 34 kDa beta subunit (Entrez Gene ID: 3082). Its peri- toneal permeability is expected to be poor, and so the HGF protein detected in the eﬄuent may be produced locally. Yu et al. demonstrated that human peritoneal mesothelial cells constitutively synthesized HGF [4]. In a previous study, high-glucose-induced EMT in the peritoneal mesothelium was reversed by HGF treatment, suggesting a link between decreased HGF expression and EMT in human peritoneal mesothelial cells [4]. HGF also prevented peritoneal ﬁbrosis in a rat model of EPS [25]. However, Rampino et al. showed that treatment with high-dosage HGF (50 pg/mL) and the HGF released during peritonitis in humans may facilitate repair through mesothelial cell growth, but may also contribute to peritoneal ﬁbrosis including cell detachment, ﬁbroblast-like phenotype changes, and collagen synthesis [26]. These ﬁndings suggest that an antiﬁbrotic eﬀect of HGF may be dosage dependent with variable therapeutic dosages that depend on experimental conditions and types of animal model. We considered that unexpected increase in the HGF levels has been proposed as a compensatory mechanism in patients with high peritoneal transport rate. High eﬄuent HGF may be a marker of peritoneal deterioration since high HGF levels coexist with high peritoneal transport rate. In contrast with Szeto et al.’s report [27], no diﬀerence in BMP-7 was demonstrated by the diﬀerence in D/P creatinine in our study. Their results showed that the PD eﬄuent BMP- 7 level displayed a signiﬁcant correlation with the change in the D/P creatinine level but was not signiﬁcantly correlated with the D/P creatinine level at 4 or 52 weeks in new PD patients. However, we only studied the D/P creatinine level in incident CAPD patients at one time point, which may account for our diﬀerent results. We consider that it is diﬃcult to interpret EMT using measurements of eﬄuent BMP-7 concentrations taken at one time point alone. The number or mass of mesothelial cells could aﬀect the levels of intraperitoneal growth factors in CAPD patients.