Natural History of Proteinuria in Renal Transplant Recipients Developing De Novo Human Leukocyte Antigen Antibodies

Background. The relationship between humoral rejection and human leukocyte antigen (HLA) antibodies is established. Proteinuria is the hallmark of glomerular injury. The relationship between HLA antibody and proteinuria was explored in renal transplant recipients developing de novo donor-specific antibodies (DSA) and nondonor-specific antibodies (NDSA). Methods. Seventy-two patients with de novo HLA antibody (38 DSA and 34 NDSA) were identified from 475 prevalent renal transplant recipients (15.2%). Antibody surveillance occurred every 6 months, with specificity characterized by a combination of enzyme-linked immunosorbent assay, flow-bead cytometry, and Luminex bead analysis. Pooled analysis of every glomerular filtration rate (GFR) and urinary protein estimation in a 48-month window around the date of antibody detection was performed (4004 and 2084 measurements, respectively). Results. GFR slope (-5.85 vs. -3.21 mL/min/1.73 m(2) per year) and graft failure rate (29% vs. 9%, P=0.039) were worse in patients with DSA. Three-year graft survival after antibody detection was worse in patients with DSA (69.5% vs. 91.1%, P=0.035). Patients with DSA had significantly more proteinuria than those with NDSA and 205 control patients with no alloantibodies, from 6 months before antibody detection (0.91 vs. 0.39 g/L, P=0.015). Graft failure was more likely in patients with DSA with excess of 0.2 g/L at antibody detection (42% vs. 0%, P=0.008). Conclusions. Proteinuria is associated with DSA detection and is likely to be an important factor that determines rapid GFR decline and earlier graft failure in patients developing de novo HLA antibodies.