case_images: PMC10631334_01
case_images: Clinical course before and after application of daratumumab. (a) Summary of events and therapy before and after transplantation including five IA and four PPH sessions for desensitization, rituximab (375 mg/m2), biopsies, ABMR therapy with prednisolone pulse (250 mg/kg body weight), post-transplant PPH, ABO-A antibody-selective IA and application of daratumumab (each 1800 mg s.c.). Serum-Creatinine levels after transplantation. (b) Histopathological images of the transplant biopsies performed on day 5, 14, and 62 after transplantation (I-XII). First biopsy (I-VI) on post-transplant day 5 with morphological features of C4d-positive active ABMR (BANFF 2019 classification: g2 i1 ti2 i-IFTA2 t1 t-IFTA1 v1 ptc2 aah2 cg1 ci1 ct1 cv2 mm0). I: transplant glomerulitis (g2). PAS x 20. II: peritubular capillaritis (ptc2). PAS x 40. III: Focal interstitial inflammation and hemorrhage. HE x 20. IV: Mild endothelialitis. HE x 40. V, VI: Strong diffuse C4d-positivity of peritubular capillaries (C4d3, V: x 20, VI: x 40). Second biopsy (VII, IX, XI) on post-transplant day 14 (BANFF 2019 classification: g1 i1 ti1 i-lFTA0 t-lFTA0 t0 v0 ptc2 aah0 cg0 ci0 ct0 cv1 mm0) and third biopsy (VIII, X, XII) on post-transplant day 62 with markedly improved morphology (BANFF 2019 classification: g1 ptc0 v0 t0 i0 ti0 t-IFTA0 iIFTA0 cg1 cv0 ct1 ci1 aah0 mm1). VII: Mild focal transplant glomerulitis (g1). PAS x 20; VIII: Focal-segmental glomerular thrombotic microangiopathy ( ) and mild transplant glomerulitis (g1). HE x 20. IX: Focal mild peritubular capillaritis (ptc1). PAS x 40. X: No peritubular capillaritis (ptc0). HE x 40. XI: Diffuse C4d-positivity of peritubular capillaries (C4d3, XI: x 40). XII: Weaker diffuse C4d-positivity of peritubular capillaries (C4d2, XII: x 40).. aah: arteriolar hyalinosis; ABMR: antibody-mediated rejection; cg: chronic glomerulopathy (transplant glomerulopathy); ci: interstitial fibrosis in cortex; ct: tubular atrophy in cortex; g: glomerulitis; i: inflammation in non-scarred cortex; IA: immunoadsorption; i-IFTA: inflammation in areas of the cortex with interstitial fibrosis and tubular atrophy; mm: mesangial matrix expansion; PPH: plasmapheresis; ptc: peritubular capillaritis; t: tubulitis in cortical tubules within non-scarred cortex; t-IFTA: tubulitis in areas of the cortex with interstitial fibrosis and tubular atrophy; v: endarteritis (intimal arteritis).
case_images: 10.1177_2050313X231211050-fig1.jpg
case_images: PMC10631334_01_10.1177_2050313X231211050-fig1.jpg
case_images: fig1-2050313X231211050
case_images: Due to the high-risk immune constellation with HLA- and ABO-incompatibility, an extended desensitization protocol with five IA (Immusorba ) and four PPH sessions (Plasmaflo ) was performed preoperatively (Figure 1(a)). Initially, renal function improved gradually; however, on day 5 after transplantation, a rapid increase of Serum-creatinine (S-creatinine) from 1.8 mg/dL on day 4 to 3.4 mg/dL was observed (Figure 1(a)). The graft biopsy performed on the same day indicated severe C4d-positive and hemorrhagic ABMR associated with inflammation and intimal arteritis (Figure 1(b)). A IgM titer 1:2 and IgG titer 1:8 after the last IA on day 12), where a second graft-biopsy was performed (Figure 1(b)). In the subsequent course, three further doses of daratumumab were administered on days 15, 23, and 30. An abdominal wound dehiscence after laparotomy occurred on day 30 requiring operative revision. The third graft biopsy conducted on day 62 showed further improvement of ABMR-related changes (Figure 1(b)).
case_images: Antibody measurements. (a) Anti-A IgG- and IgM blood group antibody titers post-transplant. (b) Donor-specific antibody (DSA) level against HLA-DRB1*01:01 in mean fluorescence intensity (MFI) measured on post-transplant day 5 (before application of daratumumab) and on post-transplant day 49 (after application of daratumumab). Cut-off for post-transplant DSA positivity is shown by dotted red line.
case_images: 10.1177_2050313X231211050-fig2.jpg
case_images: PMC10631334_01_10.1177_2050313X231211050-fig2.jpg
case_images: fig2-2050313X231211050
case_images: The rise in S-creatinine was accompanied by a marked rebound of anti-blood group A antibody levels (peak IgM titer 1:8 and IgG titer 1:32) despite PPH and adequate tacrolimus trough levels of 13.4 mug/L on day 6 and 10.2 mug/L on day 8 (Figure 2(a)).