Advanced age of renal transplant recipients correlates with increased plasma concentrations of interleukin-6, chemokine ligand 2 (CCL2), and matrix metalloproteinase 2, and urine concentrations of CCL2 and tissue inhibitor of metalloproteinase 1.
BACKGROUND
Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging.


OBJECTIVE
The aim of the study was to assess the impact of a RTR's age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system.


METHODS
One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearman's (rs) rank correlation were applied, and differences with a P < .05 were considered statistically significant.


RESULTS
There was a weak but significant positive correlation between increasing RTR's age and plasma IL-6 (rs = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017), as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014) concentrations.


CONCLUSIONS
Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland. Electronic address: o.mazanowska@gmail.com.
O
O
Mazanowska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
M
M
Zabińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
K
K
Kościelska-Kasprzak
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
D
D
Kamińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
M
M
Banasik
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
M
M
Krajewska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
K
K
Madziarska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
S C
SC
Zmonarski
Department of Vascular, General and Transplant Surgery, Wroclaw Medical University, Poland.
P
P
Chudoba
Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, (ICM UW), Poland.
P
P
Biecek
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
M
M
Boratyńska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
M
M
Klinger
D000328:Adult; D018932:Chemokine CCL2 / Q000097:blood* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000652:urine*; D019716:Tissue Inhibitor of Metalloproteinase-2; D066027:Transplant Recipients
D018932:Chemokine CCL2; D015850:Interleukin-6; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9