Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients.
BACKGROUND
The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival.


OBJECTIVE
The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months).


RESULTS
Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2) versus 53 [43-61] mL/min/1.73 m(2), P < .00001) than RTRs without proteinuria.


CONCLUSIONS
Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. Electronic address: o.mazanowska@gmail.com.
O
O
Mazanowska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Zabińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
K
K
Kościelska-Kasprzak
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
D
D
Kamińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Krajewska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Banasik
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
K
K
Madziarska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
S C
SC
Zmonarski
Department of Vascular, General and Transplant Surgery, Wroclaw Medical University, Wroclaw, Poland.
P
P
Chudoba
Interdisciplinary Centre for Mathematical and Computational Modelling University of Warsaw, Warsaw, Poland.
P
P
Biecek
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Boratyńska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Klinger
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011507:Proteinuria / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D066027:Transplant Recipients; D014184:Transplantation, Homologous
C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9