The Effective Lymphatic Absorption Rate is an Accurate and Useful Concept in the Physiology of Peritoneal Dialysis

Krediet, Raymond T.

doi:10.1177/089686080402400402

Cited by 29 publications

(18 citation statements)

References 29 publications

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“…More than a decade ago, clinical studies showed that increased lymphatic absorption was related to long-term PD and UFF [ 59 , 60 ]. However, since then, the accuracy of estimated lymphatic absorption, which is based on the disappearance rate of intraperitoneally administered macromolecules such as radioactive iodinated serum albumin or dextran, has generated considerable debate [ 61 , 62 ]. Subsequently, there has been a reduced focus on the lymphatics of PD.…”

Section: Roles Of Renal and Peritoneal Lymphaticsmentioning

confidence: 99%

Roles of the TGF-β–VEGF-C Pathway in Fibrosis-Related Lymphangiogenesis

Kinashi

Ito

Sun

et al. 2018

IJMS

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Lymphatic vessels drain excess tissue fluids to maintain the interstitial environment. Lymphatic capillaries develop during the progression of tissue fibrosis in various clinical and pathological situations, such as chronic kidney disease, peritoneal injury during peritoneal dialysis, tissue inflammation, and tumor progression. The role of fibrosis-related lymphangiogenesis appears to vary based on organ specificity and etiology. Signaling via vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor (VEGFR)-3 is a central molecular mechanism for lymphangiogenesis. Transforming growth factor-β (TGF-β) is a key player in tissue fibrosis. TGF-β induces peritoneal fibrosis in association with peritoneal dialysis, and also induces peritoneal neoangiogenesis through interaction with VEGF-A. On the other hand, TGF-β has a direct inhibitory effect on lymphatic endothelial cell growth. We proposed a possible mechanism of the TGF-β–VEGF-C pathway in which TGF-β promotes VEGF-C production in tubular epithelial cells, macrophages, and mesothelial cells, leading to lymphangiogenesis in renal and peritoneal fibrosis. Connective tissue growth factor (CTGF) is also involved in fibrosis-associated renal lymphangiogenesis through interaction with VEGF-C, in part by mediating TGF-β signaling. Further clarification of the mechanism might lead to the development of new therapeutic strategies to treat fibrotic diseases.

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Section: Roles Of Renal and Peritoneal Lymphaticsmentioning

confidence: 99%

Roles of the TGF-β–VEGF-C Pathway in Fibrosis-Related Lymphangiogenesis

Kinashi

Ito

Sun

et al. 2018

IJMS

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“…Clinical studies have shown that higher lymphatic absorption is associated with lower effective ultrafiltration 9 and UFF 10 . However, the results from these clinical approaches are controversial 11,12 , and the process of lymphangiogenesis remains poorly understood. We therefore investigated whether lymphangiogenesis is associated with peritoneal fibrosis 13 .…”

Section: Introductionmentioning

confidence: 99%

Connective tissue growth factor is correlated with peritoneal lymphangiogenesis

Kinashi

Toda

Sun

et al. 2019

Sci Rep

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Lymphatic absorption in the peritoneal cavity may contribute to ultrafiltration failure in peritoneal dialysis (PD). Lymphatic vessels develop during PD-related peritoneal fibrosis. Connective tissue growth factor (CTGF, also called CCN2) is an important determinant of fibrotic tissue remodeling, but little is known about its possible involvement in lymphangiogenesis. In this study, we investigated the relationship between CTGF and peritoneal lymphangiogenesis. A positive correlation was observed between vascular endothelial growth factor-C (VEGF-C), a major lymphangiogenic growth factor, and the CTGF concentration in human PD effluents. CTGF expression was positively correlated with expression of lymphatic markers and VEGF-C in human peritoneal biopsies. We found a positive correlation between the increase in CTGF and the increase in VEGF-C in cultured human peritoneal mesothelial cells (HPMCs) treated with transforming growth factor-β1 (TGF-β1). The diaphragm is a central player in peritoneal lymphatic absorption. CTGF expression was also correlated with expression of VEGF-C and lymphatics in a rat diaphragmatic fibrosis model induced by chlorhexidine gluconate (CG). Furthermore, CTGF gene deletion reduced VEGF-C expression and peritoneal lymphangiogenesis in the mouse CG model. Inhibition of CTGF also reduced VEGF-C upregulation in HPMCs treated with TGF-β1. Our results suggest a close relationship between CTGF and PD-associated lymphangiogenesis.

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“…The longitudinal design offers clear advantages and a relatively novel approach, but has some drawbacks, including a risk for selective biases, due to a significant proportion of patients lost during follow-up. Moreover, the modified PET-based analysis did not permit direct estimations of lymphatic absorption rates, which demand specific methodologic approaches, beyond routine clinical practice (22). Despite these limitations, the study offers a longitudinal view of water transport in patients with UFF since the inception of PD, contributing to a clearer knowledge of this disorder.…”

Section: Discussionmentioning

confidence: 99%