Urinary C4d does not correlate with C4d-staining in peritubular capillaries but reflects nonspecific glomerular injury.
BACKGROUND
C4d-staining in peritubular capillaries (PTC) in allograft biopsies is a hallmark of antibody-mediated rejection (AMR). This study investigated whether urinary C4d correlates with C4d-staining in PTC, allowing for a noninvasive screening procedure.


METHODS
Urine samples from 34 patients with diffuse C4d-staining in PTC (C4d-pos group) and 68 urine samples from patients with negative C4d-staining in PTC (C4d-negative group) matched 1:2 according to proteinuria and time posttransplant were compared regarding urinary C4d-levels.


RESULTS
Overall, urinary C4d/creatinine-ratios (C4d/C) were not different between the C4d-positive and the C4d-negative group (P=0.55). Urinary C4d/C strongly correlated with total protein/creatinine-ratios (P/C) (r2=0.53; P<0.0001) and albumin/creatinine-ratios (r2=0.52; P<0.0001). C4d/C were not different between C4d-pos and C4d-negative patients with P/C>50 mg/mmol (P=0.57) and P/C<50 mg/mmol (P=0.65), respectively. However, in both the C4d-positive and the C4d-negative group urinary C4d/C were significantly higher in patients with P/C>50 mg/mmol than in patients with P/C<50 mg/mmol (P<or=0.005). Furthermore, longitudinal analysis in 3 patients with distinct clinico-pathological courses demonstrated that urinary C4d/C closely followed P/C regardless of C4d-staining in PTC.


CONCLUSIONS
Urinary C4d does not correlate with C4d-staining in PTC but reflects nonspecific glomerular injury. Therefore, urinary C4d is likely not a useful biomarker for non-invasive screening and monitoring of AMR.
Hönger
Gideon
G
Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Mayr
Michael
M
Dickenmann
Michael
M
Mihatsch
Michael J
MJ
Schaub
Stefan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D002196:Capillaries / Q000473:pathology*; D015935:Complement C4b / Q000032:analysis* / Q000652:urine*; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis* / Q000652:urine*; D011183:Postoperative Complications / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D003404:Creatinine