Observational Study
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World J Nephrol. Mar 6, 2016; 5(2): 204-212
Published online Mar 6, 2016. doi: 10.5527/wjn.v5.i2.204
Matrix metalloproteinase-2 as a superior biomarker for peritoneal deterioration in peritoneal dialysis
Ichiro Hirahara, Eiji Kusano, Yoshiyuki Morishita, Makoto Inoue, Tetsu Akimoto, Osamu Saito, Shigeaki Muto, Daisuke Nagata
Ichiro Hirahara, Eiji Kusano, Yoshiyuki Morishita, Makoto Inoue, Tetsu Akimoto, Osamu Saito, Shigeaki Muto, Daisuke Nagata, Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
Author contributions: All authors contributed to the drafting and approval of the manuscript; Kusano E and Nagata D managed this multicenter clinical study; Morishita Y, Inoue M, Akimoto T, Saito O and Muto S collected the patients’ clinical data and samples; Hirahara I analyzed the biomarker levels and data and wrote this paper.
Institutional review board statement: This clinical study was reviewed and approved by the Ethics Committee of Jichi Medical University (No. 04-45).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Ichiro Hirahara is affiliated with Terumo Core Technology Center (Kanagawa, Japan).
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ichiro Hirahara, Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. hirahara@rpf.jp
Telephone: +81-0285-587346 Fax: +81-0285-444869
Received: August 27, 2015
Peer-review started: August 31, 2015
First decision: September 28, 2015
Revised: November 5, 2015
Accepted: December 18, 2015
Article in press: December 20, 2015
Published online: March 6, 2016
Processing time: 186 Days and 18.8 Hours
Abstract

AIM: To investigate the efficacy of effluent biomarkers for peritoneal deterioration with functional decline in peritoneal dialysis (PD).

METHODS: From January 2005 to March 2013, the subjects included 218 PD patients with end-stage renal disease at 18 centers. Matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), hyaluronan, and cancer antigen 125 (CA125) in peritoneal effluent were quantified with enzyme-linked immunosorbent assay. Peritoneal solute transport rate was assessed by peritoneal equilibration test (PET) to estimate peritoneal deterioration.

RESULTS: The ratio of the effluent level of creatinine (Cr) obtained 4 h after injection (D) to that of plasma was correlated with the effluent levels of MMP-2 (ρ = 0.74, P < 0.001), IL-6 (ρ = 0.46, P < 0.001), and hyaluronan (ρ = 0.27, P < 0.001), but not CA125 (ρ = 0.13, P = 0.051). The area under receiver operating characteristic curve for the effluent levels of MMP-2, IL-6, and hyaluronan against high PET category were 0.90, 0.78, 0.62, and 0.51, respectively. No patient developed new-onset encapsulating peritoneal sclerosis for at least 1.5 years after peritoneal effluent sampling.

CONCLUSION: The effluent MMP-2 level most closely reflected peritoneal solute transport rate. MMP-2 can be a reliable indicator of peritoneal deterioration with functional decline.

Keywords: Encapsulating peritoneal sclerosis; Matrix metalloproteinase-2; Peritoneal dialysis; Peritoneal solute transport; Peritoneal deterioration

Core tip: Peritoneal effluent samples were obtained from 218 peritoneal dialysis (PD) patients with end-stage renal disease at 18 centers. The effluent levels of biomarkers matrix metalloproteinase-2 (MMP-2), interleukin-6, hyaluronan, and cancer antigen 125 were measured. Peritoneal solute transport rate was assessed by peritoneal equilibration test (PET) to estimate peritoneal deterioration. Among the biomarkers in the effluent, MMP-2 level correlated most significantly with peritoneal solute transport rate. The area under the receiver operating characteristic curve analysis for effluent MMP-2 level against high PET category was 0.90. MMP-2 may be a superior biomarker for peritoneal deterioration during PD.