The potential of matrix metalloproteinase-2 as a marker of peritoneal injury, increased solute transport, or progression to encapsulating peritoneal sclerosis during peritoneal dialysis--a multicentre study in Japan.
BACKGROUND
Long-term peritoneal dialysis (PD) leads to peritoneal injury. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. The mortality rate of EPS is extremely high. To perform PD safely, monitoring of peritoneal injury that leads to EPS is a necessity.


METHODS
A total of 444 PD patients with end-stage renal disease at 60 centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the peritoneal effluents were analysed with gelatin zymography or enzyme-linked immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute transport was assessed with the peritoneal equilibration test (PET).


RESULTS
The MMP-2 levels in peritoneal effluents obtained with the PET were significantly correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio (R = -0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury, moderate peritoneal injury, severe peritoneal injury (EPS) and infectious peritonitis were significantly higher than those in control patients (P < 0.001, P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The peritoneal effluents from patients with infectious peritonitis showed strong MMP-9 signals.


CONCLUSIONS
From these results, MMP-2 levels in peritoneal effluents reflect peritoneal solute transport and changes in MMP-2 levels are associated with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of peritoneal injury, increased solute transport or progression to EPS.
Hirahara
Ichiro
I
Division of Nephrology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-city, Tochigi 329-0498, Japan. hirahara@rpf.jp
Inoue
Makoto
M
Okuda
Kousuke
K
Ando
Yasuhiro
Y
Muto
Shigeaki
S
Kusano
Eiji
E
D000368:Aged; D001202:Ascitic Fluid / Q000201:enzymology*; D001693:Biological Transport, Active / Q000502:physiology; D015314:Dialysis Solutions / Q000493:pharmacokinetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000628:therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000201:enzymology* / Q000453:epidemiology / Q000473:pathology; D010537:Peritoneum / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012598:Sclerosis; D013997:Time Factors
D015314:Dialysis Solutions; D020778:Matrix Metalloproteinase 2