Non-invasive monitoring of renal transplant recipients: urinary excretion of soluble adhesion molecules and of the complement-split product C4d.
BACKGROUND
The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients.


METHODS
Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: GROUP 1: acute steroid-sensitive rejection (ASSR, n = 14), GROUP 2: acute steroid-resistant rejection (ASRR, n = 12), GROUP 3: chronic allograft dysfunction (CAD, n = 20) and GROUP 4: stable graft function (SGF, n = 29).


RESULTS
All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p < 0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p < 0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p < 0.05).


CONCLUSIONS
The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment.
Lederer
Stephan R
SR
Medizinische Klinik-Innenstadt, Klinikum der Universität München, München, Deutschland. stephan.lederer@medinn.med.uni-muenchen.de
Friedrich
Nicole
N
Regenbogen
Claudia
C
Getto
Rainer
R
Toepfer
Marcel
M
Sitter
Thomas
T
D000328:Adult; D015415:Biomarkers / Q000652:urine; D015815:Cell Adhesion Molecules / Q000652:urine*; D003181:Complement C4 / Q000652:urine*; D015935:Complement C4b; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000145:classification / Q000175:diagnosis / Q000652:urine; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000652:urine; D016030:Kidney Transplantation / Q000379:methods*; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D010446:Peptide Fragments / Q000652:urine*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000652:urine
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003181:Complement C4; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015935:Complement C4b; C032261:complement C4d