Peritoneal injury by methylglyoxal in peritoneal dialysis.
BACKGROUND
Peritonealdialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo.


METHODS
Male Sprague-Dawley rats (n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed.


RESULTS
In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels.


CONCLUSIONS
MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.
Hirahara
Ichiro
I
Department of Nephrology, Jichi Medical School, Kawachi-gun, Tochigi, Japan. hirahara@rpf.jp
Kusano
Eiji
E
Yanagiba
Satoru
S
Miyata
Yukio
Y
Ando
Yasuhiro
Y
Muto
Shigeaki
S
Asano
Yasushi
Y
D000818:Animals; D015314:Dialysis Solutions / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D023421:Models, Animal; D010529:Peritoneal Cavity / Q000502:physiology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D011765:Pyruvaldehyde / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015314:Dialysis Solutions; D011765:Pyruvaldehyde; D005947:Glucose