The effect of low glucose degradation product dialysis solution on epithelial-to-mesenchymal transition in continuous ambulatory peritoneal dialysis patients.
BACKGROUND
Human peritoneal mesothelial cells (HPMCs) undergo a transition from an epithelial phenotype to a mesenchymal phenotype (EMT) during peritoneal dialysis (PD). That transition may be directly related to failure of peritoneal membrane function.


OBJECTIVE
In a randomized prospective controlled study, we investigated the effect of low glucose degradation product (GDP) dialysis solution on the transition of HPMCs.


METHODS
Among new continuous ambulatory PD patients, 60 patients completed a 12-month protocol (low-GDP solution group, n = 32; high-GDP solution group, n = 28). At the 1st, 6th, and 12th months, HPMCs drained from overnight effluent were cultured on T25. When they had nearly reached confluence, cell scores were measured blindly by the same person (score 1 = cobblestone-shaped HPMCs, score 2 = mixed, score 3 = fibroblast dominant). Cell scores and clinical indices, including peritoneal markers, were compared between the low-GDP and high-GDP groups at the 1st, 6th, and 12th months. The factors associated with EMT were analyzed with generalized estimating equations using STATA 7.0 (STATA Corp., College Station, Texas, USA). In addition, vimentin and cytokeratin 8/18 stains were used to verify EMT in cultured cells and peritoneal specimens in some patients.


RESULTS
(1) The low-GOP group showed higher dialysate cancer antigen 125 levels from the 1st to 12th months (55.4 +/- 24.8 vs 8.8 +/- 1.7, 56.7 +/- 28.1 vs 22.1 +/- 11.3, and 54.2 +/- 28.2 vs 24.6 +/- 16.5 U/mL, at the 1st, 6th, and 12th months, respectively; all p = 0.000). (2) The low-GOP group showed lower cell scores at the 1st, 6th, and 12th months (1.22, 1.22, and 1.56 vs 1.61, 1.75, and 2.14; p < 0.05, p < 0.01, and p < 0.01, respectively). (3) At the 12th month, the number of fibroblast-dominant cultures (score 3) was significantly lower in the low-GOP group [4/32 (12.5%) patients vs 14/28 (50%), p < 0.05]. (4) Both cobblestone-shaped HPMCs and fibroblastoid cells were positively stained with cytokeratin and vimentin. (5) There were many cytokeratin- and vimentin-positive cells in the submesothelial area in the peritoneal biopsy specimens. (6) The consistent factor associated with EMT was only high-GOP solution (60 patients, n = 178, beta coefficient 0.312, p = 0.000; 46 patients, n = 137, beta coef: 0.228, p = 0.000) and not numbers of peritonitis episodes, duration of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker medication, or diabetes.


CONCLUSIONS
Low-GDP solution showed beneficial effects such as rapid remesothelialization and less EMT in the peritoneum with time on PD.
Do
Jun-Young
JY
Department of Internal Medicine, Yeungnam University Hospital, Daegu, Korea. jydo@med.yu.ac.kr
Kim
Yong-Lim
YL
Park
Jong-Won
JW
Cho
Kyu-Hyang
KH
Kim
Tae-Woo
TW
Yoon
Kyung-Woo
KW
Kim
Chan-Duck
CD
Park
Sun-Hee
SH
Han
Jin-Hyun
JH
Song
In-Han
IH
D000328:Adult; D000368:Aged; D015415:Biomarkers; D018394:CA-125 Antigen; D015314:Dialysis Solutions / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects*; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000379:methods*; D010537:Peritoneum / Q000187:drug effects*; D011446:Prospective Studies; D016037:Single-Blind Method
D015415:Biomarkers; D018394:CA-125 Antigen; D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced