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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Blanka Mező; Andreas Heilos; Georg A Böhmig; Farsad Eskandary; Markus Wahrmann; Gregor Bond; Nicolas Kozakowski; Philip F Halloran; Krisztina Rusai; Zoltán Prohászka Journal: Transplant Direct Date: 2019-06-27