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Part 3: Clinical Experiences |
Division of Nephrology, Kyungpook National University Hospital School of Medicine, Daegu, Korea
Correspondence to: Y.L. Kim, Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital, 50, Samduk-dong 2Ga, Jung-gu, Daegu 700-721 Korea. ylkim{at}knu.ac.kr
Ultrafiltration failure (UFF) continues to be a major complication of
peritoneal dialysis (PD), particularly long-term PD. Continuous exposure to
bioincompatible PD solutions causes inflammation of the peritoneal membrane,
which progressively undergoes fibrosis and angiogenesis and, ultimately, UFF.
There is emerging evidence that epithelial–mesenchymal transition (EMT)
of peritoneal mesothelial cells (MCs) may play an important role in the
failure of peritoneal membrane function. Submesothelial myofibroblasts
originating from MCs through EMT and from activated resident fibroblasts
participate in inflammatory responses, extracellular matrix accumulation, and
angiogenesis. High glucose and glucose degradation products from PD solutions
are responsible for production of transforming growth factor β
(TGFβ) and vascular endothelial growth factor (VEGF) by MCs, which induce
EMT. Leptin and receptor for advanced glycation end-products (AGEs) augment
myofibroblastic conversion through the TGFβ signaling system.
A reduction in osmotic conductance in addition to increased solute
transport causes UFF. This situation may be caused by loss of aquaporin (AQP)
function and formation of the submesothelial fibrotic layer. During PD, AQP1
plays an essential role in water permeability and ultrafiltration (UF),
modulating processes such as endothelial permeability and angiogenesis. During
a hypertonic dwell, AQP1 mediates 50% of UF. Insufficient AQP1 function may be
causative for inadequate UFF. A significant amount of evidence from animal
studies now exists to show that mast cells communicate with fibroblasts and
are implicated in fibrogenesis, angiogenesis, and UFF. However, it is not
confirmed in human studies that mast cells contribute to the fibrosis seen in
the peritoneum of PD patients.
The patterns of UFF in PD patients depend on duration of treatment.
Inherently high small-solute transport status is associated with
hypoalbuminemia and a greater comorbidity index. However, most of the
variability in peritoneal transport remains unexplained, pointing to the
potential role of genetic factors. Gene polymorphisms associated with
peritoneal membrane transport have been identified. Recent studies have shown
that VEGF, interleukin-6, endothelial NO synthase, AGE receptor, and
RAS gene polymorphisms are associated with transport properties in PD
patients. Current insights into the mechanisms of UFF will provide rationales
for new therapeutic strategies.
KEY WORDS: Ultrafiltration failure; epithelial-to-mesenchymal transition; aquaporin.
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