Peritoneal dialysis-related gastrointestinal complication and novel therapy on epithelial-mesenchymal transition process during peritoneal damage

  • 李 宜哲

Student thesis: Doctoral Thesis

Abstract

Peritoneal dialysis (PD) is one type of renal replacement therapy that has its own novel advantages The characteristics of this therapy include increases in patients’ intraabdominal pressure and long-term exposure of both the peritoneum and gastrointestinal (GI) organs to bio-incompatible dialysate directly or indirectly all of which may induce potential peritoneum or GI organ adverse effects Studies have shown that some GI diseases common occur in PD patients but whether the risk of common GI diseases and cancers differs among PD hemodialysis (HD) and non-uremic groups remains uncertain Therefore in the first part of our study we conducted a large-scale retrospective cohort study using data from a nationwide database from the Taiwan National Health Insurance Research Database (NHIRD) which enrolled almost all the dialysis patients in the country Subsequently we investigated whether PD therapy was an independent risk factor for common GI diseases and GI cancers The main findings of our study were that the risk of gastroesophageal reflux (GERD) intestinal obstruction or adhesions and abdominal hernia was significantly higher in the PD group whereas the risk of peptic ulcer disease and lower GI diverticula and bleeding was significantly greater in the HD group Meanwhile the risk of mesenteric ischemia liver cirrhosis and acute pancreatitis was higher in dialysis patients but this risk was not significantly different between the PD and HD groups Moreover the risk of appendicitis in the PD group appeared to be lower than that in the HD group Our cancer risk study showed that the risk of hepatocellular carcinoma bladder cancer and extra kidney and bladder urinary tract cancer was higher in both HD and PD patients while the risk of both kidney and thyroid cancers was only higher in the HD group In summary our results indicated that dialysis patients had a higher risk of some types of GI disease and cancers and different dialysis modalities affected the clinical results differently The above study demonstrated that peritoneal damage related intestinal obstruction or adhesion is one of the most common complications in PD patients Therefore in the second part of our study we focused on this common and important complication and tried to investigate a novel therapy for this complication There is substantial evidence that the epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role in the peritoneal damage process and some studies in the cancer field have proved that vitamin D can inhibit the EMT process in cancer cells Consequently we investigated if vitamin D can ameliorate peritoneal damage by inhibiting the EMT of MCs both in vitro and in vivo The results showed that 1? 25(OH)2D3 inhibited chlorhexidine gluconate (CG)-induced peritoneal morphological and functional deterioration in an animal model along with CG-induced upregulation of ?-SMA and downregulation of E-cadherin expression Meanwhile 1? 25(OH)2D3 also inhibited the transforming growth factor-β1-induced decrease in E-cadherin expression increase in both Snai1 and ?-SMA expression redistribution of intracellular F-actin and migration activity in vitro In conclusion our study proved that dialysis patients have a higher risk of the most common GI diseases and some types of cancer while both PD and HD modalities are associated with the incidence of different GI diseases and cancers Besides peritoneal damage-related intestinal obstruction or adhesion was an important and common complication in PD patients Intraperitoneal supply of 1? 25(OH)2D3 seems to be one of the potential novel solutions to this complication
Date of Award2016 七月 15
語言English
SupervisorSheng-Hsiang Lin (Supervisor)

引用此文

Peritoneal dialysis-related gastrointestinal complication and novel therapy on epithelial-mesenchymal transition process during peritoneal damage
宜哲, 李. (Author). 2016 七月 15

Student thesis: Doctoral Thesis