case_images: PMC11325154_01
case_images: Case summary including key clinical events, allograft biopsy results, therapeutic interventions, routine biomarkers (creatinine, urine albumin/creatinine ratio) as well as donor-derived cell-free DNA (dd-cfDNA). The red shaded area depicts the absolute dd-cfDNA levels and numeric values are provided at the top of the figure. The prespecified cut-off of 50 copies/mL derived from previous validation studies is shown. Grey arrowheads indicate therapeutic interventions, black arrowheads indicate clinical events including kidney allograft biopsies. Orange shape indicate the time periods when DSA MFI were above 1,500. dd-cfDNA, donor-derived cell-free DNA; cp, copies; D0, day of transplantation; M, months after transplantation; DSA, donor-specific anti-HLA antibodies; dnDSA, de novo DSA; KTX, kidney transplantation; PLEX, plasma exchange; IVIG, intravenous immunoglobulins; ATG, anti-thymocyte globulin; Mixed Rej., mixed rejection; aAMR, active antibody-mediated rejection; TCMR, T-cell mediated rejection; UTI, urinary tract infection; caAMR, chronic active antibody-mediated rejection; MMF, mycophenolate mofetil.
case_images: ti-37-13213-g001.jpg
case_images: PMC11325154_01_ti-37-13213-g001.jpg
case_images: F1
case_images: Preformed DSA declined to an MFI of 1,564, which was deemed sufficiently low to perform transplantation (Figure 1).
case_images: Representative histopathological findings for patient 1 showing glomerulitis (g), peritubular capillaritis (ptc), chronic transplant glomerulopathy (cg), and intimal arteritis (v) at (A) 9 months after transplantation (before daratumumab) and (B) 15 months after transplantation (6 months after treatment with daratumumab).
case_images: ti-37-13213-g002.jpg
case_images: PMC11325154_01_ti-37-13213-g002.jpg
case_images: F2
case_images: A third kidney biopsy confirmed ongoing chronic active AMR (caAMR) with severe transplant glomerulopathy (cg3), severe glomerulitis (g3), severe peritubular capillaritis (ptc3), mild to moderate intimal arteritis (v1), matching the high dd-cfDNA levels (Figure 2A) (g3ptc3v1t0i1ti1tIFTA0iIFTA0cg3mm0cv1aah3ct1ci1).
case_images: Case summary including key clinical events, allograft biopsy results, therapeutic interventions, routine biomarkers (creatinine, urine albumin/creatinine ratio) as well as donor-derived cell-free DNA (dd-cfDNA). The red shaded area depicts the absolute dd-cfDNA levels and numeric values are provided at the top of the figure. The prespecified cut-off of 50 copies/mL derived from previous validation studies is shown. Grey arrowheads indicate therapeutic interventions, black arrowheads indicate clinical events including kidney allograft biopsies. Orange shape indicate the time periods when DSA MFI were above 1,500. dd-cfDNA, donor-derived cell-free DNA; cp, copies; D0, day of transplantation; M, months after transplantation; DSA, donor-specific anti-HLA antibodies; KTX, kidney transplantation; PLEX, plasma exchange; IVIG, intravenous immunoglobulins; RTX, rituximab; aAMR, active antibody-mediated rejection; cAMR, chronic inactive antibody-mediated rejection; MMF, mycophenolate mofetil.
case_images: ti-37-13213-g003.jpg
case_images: PMC11325154_02_ti-37-13213-g003.jpg
case_images: F3
case_images: Despite well matched graft (mismatch grade HLA-A, -B, -C, -DR, -DQ 1-1-1-0-0) within the Acceptable Mismatch (AM) program, two preformed DSA were present (Cw6; MFI 1743, DP2; MFI 8890) after transplantation (Figure 3).
case_images: PMC11325154_02
case_images: Case summary including key clinical events, allograft biopsy results, therapeutic interventions, routine biomarkers (creatinine, urine albumin/creatinine ratio) as well as donor-derived cell-free DNA (dd-cfDNA). The red shaded area depicts the absolute dd-cfDNA levels and numeric values are provided at the top of the figure. The prespecified cut-off of 50 copies/mL derived from previous validation studies is shown. Grey arrowheads indicate therapeutic interventions, black arrowheads indicate clinical events including kidney allograft biopsies. Orange shape indicate the time periods when DSA MFI were above 1,500. dd-cfDNA, donor-derived cell-free DNA; cp, copies; D0, day of transplantation; M, months after transplantation; DSA, donor-specific anti-HLA antibodies; KTX, kidney transplantation; PLEX, plasma exchange; IVIG, intravenous immunoglobulins; RTX, rituximab; aAMR, active antibody-mediated rejection; cAMR, chronic inactive antibody-mediated rejection; MMF, mycophenolate mofetil.
case_images: ti-37-13213-g003.jpg
case_images: PMC11325154_02_ti-37-13213-g003.jpg
case_images: F3
case_images: Despite well matched graft (mismatch grade HLA-A, -B, -C, -DR, -DQ 1-1-1-0-0) within the Acceptable Mismatch (AM) program, two preformed DSA were present (Cw6; MFI 1743, DP2; MFI 8890) after transplantation (Figure 3).
case_images: Representative histopathological findings for patient 2 showing glomerulitis (g), peritubular capillaritis (ptc), and chronic transplant glomerulopathy (cg) at (A) 12 months after transplantation (before daratumumab) and (B) 18 months after transplantation (6 months after treatment with daratumumab).
case_images: ti-37-13213-g004.jpg
case_images: PMC11325154_02_ti-37-13213-g004.jpg
case_images: F4
case_images: However, 2-3 months later, creatinine rose again (1.9-2.3 mg/dL), and a third biopsy still showed caAMR with high activity (g3ptc2v0t0i0ti0tIFTA0iIFTA0cg2mm0cv0aah0ct1ci1, Figure 4A). A fourth biopsy after 6 months of daratumumab therapy showed chronic (inactive) AMR with AMR activity being almost completely resolved (g0ptc1v0t1i0ti1iIFTA2tIFTA1cg2mm1cv1aah2ct1ci1), which is matching the dd-cfDNA results (Figure 4B).