Urinary NK Cells in Patients with Transplant Glomerulopathy with or without Donor-Specific Antibodies

Transplant glomerulopathy (TG) is a hallmark of chronic active antibody-mediated rejection (cAMR), but also occurs in the absence of donor-specific antibodies (TG/DSA-). Recently, biopsy studies have hypothesized a role for NK cells in both conditions. We investigated the possible presence of urinary NK cells (uNK) using flow cytometry in 19 cAMR and 18 TG/DSA-. uNK were significantly detected in TG patients vs. controls (transplanted patients without TG/healthy subjects); considering a uNK cutoff >1.5 cells/mg/g urinary creatinine (correlating with graft loss based on the ROC curve), the 26/37 (70.2%) uNK+ showed similar distribution in cAMR vs. TG/DSA-, and increased cg and g+ptc scores and a more pronounced decline in eGFR with significant difference at 12 months. TG/DSA-/uNK+ showed worse eGFR at diagnosis and at 12 months. In TG/uNK+, phenotypic profiling revealed a predominance of CD56dimCD16⁺ cells in both cAMR and TG/DSA⁻ (78.6% vs. 58.3%, respectively), supporting the hypothesis that circulating NK cells are mainly involved in kidney infiltration and TG pathogenesis. Taken together, our results demonstrate the presence of uNK in both cAMR and TG/DSA- but not in controls, and attempted correlations with clinical outcome and histology findings, thus supporting a peculiar role of this cell type in these conditions.