Matrix metalloproteinase-2 as a superior biomarker for peritoneal deterioration in peritoneal dialysis

Table 1 Characteristics of peritoneal dialysis patients

Characteristics of patients
Sex (male/female)	122/96 (56% male)
Etiology (non-DM/DM)	179/36 (17% diabetes)
Age (yr)	56 (20, 46, 64, 84)
PD duration (mo)	40 (1, 15, 63, 206)
Peritonitis episode (times)	0 (0, 0, 1, 9)
D/P Cr	0.65 (0.38, 0.59, 0.71, 0.88)
D/D 0 glucose	0.40 (0.21, 0.34, 0.44, 0.59)

Data except sex and etiology of renal failure are expressed as median with minimum value, interquartile range, and maximum value. PD: Peritoneal dialysis; Cr: Creatinine; DM: Diabetes mellitus; non-DM: Non-diabetes mellitus.

Table 2 Biomarker levels in the peritoneal effluent

Biomarker	Level in the peritoneal effluent
Matrix metalloproteinase-2 (ng/mL)	159 (14, 107, 220, 681)
Interleukin-6 (pg/mL)	14.6 (1.5, 7.6, 29.6, 253.5)
Hyaluronan (ng/mL)	109 (5.1, 53, 204, 889)
Cancer antigen 125 (U/mL)	6.7 (0.7, 4.0, 12.1, 91.8)

Data are expressed as median with minimum value, interquartile range, and maximum value.

Table 3 Correlation between patient characteristics and effluent biomarker levels

	Biomarker levels in the peritoneal effluents
	MMP-2	IL-6	Hyaluronan	CA125
Sex (male/female)	P = 0.92	P = 0.54	P = 0.48	P < 0.05
Etiology (non-DM/DM)	P = 0.18	P = 1.00	P = 0.56	P < 0.05
Age (yr)	ρ = 0.076	ρ = 0.12	ρ = 0.046	ρ = -0.096
	P = 0.27	P = 0.092	P = 0.50	P = 0.16
PD duration (mo)	ρ = 0.050	ρ = 0.15	ρ = 0.25	ρ = -0.062
	P = 0.47	P < 0.05	P < 0.01	P = 0.93
Peritonitis episode (times)	ρ = 0.17	ρ = 0.25	ρ = 0.092	ρ = -0.012
	P < 0.05	P < 0.001	P = 0.20	P = 0.86

ρ values were derived from Spearman’s correlation coefficient. PD: Peritoneal dialysis; MMP-2: Matrix metalloproteinase-2; IL-6: Interleukin-6; CA125: Cancer antigen 125; DM: Diabetes mellitus; non-DM: Non-diabetes mellitus.

Table 4 Correlation between effluent biomarker levels and the results of peritoneal equilibration test

	D/P Cr	D/D0 glucose	MMP-2	IL-6	Hyaluronan	CA125
D/P Cr	ρ = 1	ρ = -0.86	ρ = 0.74	ρ = 0.46	ρ = 0.27	ρ = 0.13
		P < 0.001	P < 0.001	P < 0.001	P < 0.001	P = 0.051
D/D0 Glucose		ρ = 1	ρ = -0.65	ρ = -0.28	ρ = -0.22	ρ = -0.094
			P < 0.001	P < 0.001	P < 0.005	P = 0.19
MMP-2			ρ = 1	ρ = 0.54	ρ = 0.40	ρ = 0.1
				P < 0.001	P < 0.001	P < 0.05
IL-6				ρ = 1	ρ = 0.45	ρ = 0.26
					P < 0.001	P < 0.001
Hyaluronan					ρ = 1	ρ = 0.18
						P < 0.01
CA125						ρ = 1

ρ values were calculated by Spearman’s correlation coefficient. Cr: Creatinine; MMP-2: Matrix metalloproteinase-2; IL-6: Interleukin-6; CA125: Cancer antigen 125.

Table 5 Test performance of effluent biomarkers cut-off levels to distinguish the high category of peritoneal equilibration test

Biomarkers	Cut-off level	Sensitivity (95%CI)	Specificity (95%CI)	AUC
MMP-2-	214 ng/mL	0.95 (0.86 to 1.00)	0.79 (0.74 to 0.85)	0.90
	219 ng/mL	0.86 (0.71 to 1.00)	0.81 (0.76 to 0.86)
	228 ng/mL	0.81 (0.62 to 0.95)	0.84 (0.79 to 0.89)
	238 ng/mL	0.76 (0.57 to 0.95)	0.87 (0.82 to 0.91)
IL-6	16.8 pg/mL	0.81 (0.62 to 0.95)	0.60 (0.53 to 0.67)	0.78
	19.3 pg/mL	0.76 (0.57 to 0.90)	0.65 (0.58 to 0.73)
	20.0 pg/mL	0.71 (0.52 to 0.90)	0.66 (0.60 to 0.73)
	24.8 pg/mL	0.67 (0.48 to 0.86)	0.75 (0.66 to 0.79)
Hyaluronan	94.5 ng/mL	0.81 (0.62 to 0.95)	0.47 (0.41 to 0.54)	0.62
	101.5 ng/mL	0.71 (0.52 to 0.90)	0.51 (0.44 to 0.58)
	108.0 ng/mL	0.67 (0.48 to 0.86)	0.52 (0.45 to 0.58)
	115.0 ng/mL	0.62 (0.43 to 0.81)	0.53 (0.46 to 0.53)
CA125	3.85 U/mL	0.81 (0.62 to 0.95)	0.23 (0.17 to 0.29)	0.51
	4.45 U/mL	0.71 (0.52 to 0.90)	0.30 (0.23 to 0.37)
	6.55 U/mL	0.62 (0.43 to 0.81)	0.50 (0.43 to 0.57)
	7.05 U/mL	0.52 (0.33 to 0.71)	0.53 (0.46 to 0.59)

AUC: Area under curve; MMP-2: Matrix metalloproteinase-2; IL-6: Interleukin-6; CA125: Cancer antigen 125.

Table 6 Test performance of effluent matrix metalloproteinase-2 cut-off levels to predict the encapsulating peritoneal sclerosis in peritoneal dialysis patients

Cut-off level	Sensitivity (95%CI)	Specificity (95%CI)	AUC
458.5	1.00 (1.00 to 1.00)	0.96 (0.94 to 0.98)	0.99
609.5	0.88 (0.63 to 1.00)	0.99 (0.98 to 1.00)
863.5	0.63 (0.25 to 0.88)	1.00 (0.99 to 1.00)

AUC: Area under curve.