Intravenous immunoglobulins do not prove beneficial to reduce alloimmunity among kidney transplant recipients with BKV-associated nephropathy.

Abstract

Reduced immunosuppression during BKV-DNAemia has been associated with T-cell mediated rejection (TCMR), de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). Intravenous immunoglobulins (IVIG) may reduce alloimmunity. We studied 860 kidney transplant recipients (KTRs) for the development of BKV-DNAuria and BKV-DNAemia (low-level <10000IE/ml, high-level >10000IE/ml). 52/131 KTRs with high-level BKV-DNAemia received IVIG. The HLA-related immunological risk was stratified by the Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) algorithm. BKV-DNAuria only was observed in 86 KTRs (10.0%), low-level BKV-DNAemia in 180 KTRs (20.9%) and high-level BKV-DNAemia in 131 KTRs (15.2%). KTRs with low-level BKV-DNAemia showed significantly less TCMR compared to KTRs with high-level BKV-DNAemia (5.2% vs. 25.5%; P<0.001) and no BKV-replication (13.2%; P=0.014), lowest rates of de novo DSA (21.3%), ABMR (9.2%) and flattest glomerular filtration rate (GFR) slope (-0.8ml/min). KTRs with low-level BKV-DNAemia showed significantly higher median (interquartile range) total PIRCHE if they developed TCMR [100.22 (72.6) vs. 69.52 (49.97); P=0.020] or ABMR [128.86 (52.99) vs. 69.52 (49.96); P=0.005]. Administration of IVIG did not shorten duration of BKV-DNAemia (P=0.798) or reduce TCMR, de novo DSA and ABMR (P>0.05). KTRs with low-level BKV-DNAemia showed best protection against alloimmunity, with a high number of PIRCHE co-determining the remaining risk. The administration of IVIG, however, was not beneficial in reducing alloimmunity.