Efficacy of Double Membrane Filtration Immunoadsorption in Severe C1q-Binding Donor-Specific Antibody-Positive Acute Humoral Kidney Allograft Rejection: A Case Series

Abstract

Introduction: Acute antibody-mediated rejection (ABMR) is an important threat to renal allograft survival in the early transplant period and the major single cause of graft loss in the first postoperative year. Semi-selective immunoadsorption (IA) remains one of the commonly applied treatments in ABMR, reducing allo-reactive antibody load. Adding double filtration plasmapheresis (DFPP) to IA might enhance therapeutic efficacy by also addressing innate humoral effectors like complement factors.

Methods: Four patients with ABMR were treated with DFPP + IA. Clinical, histological, and immunological data and adverse events were retrospectively collected.

Results: Here we present four high-risk treatment-refractory ABMR cases with C1q-binding donor-specific antibodies and histology of humoral rejection under treatment with DFPP + IA. While the earlier cases (within the first year after transplantation) showed marked reduction in ABMR severity and improvement of kidney function, the later cases did not respond accordingly. Late ABMR patient 1 stabilized, whereas late ABMR patient 2 did not respond to treatment.

Conclusions: Our data support the consideration of DFPP + IA as a rescue treatment option in early, severe, high-risk ABMR cases in which other treatments failed.

Keywords: Acute antibody-mediated rejection; C1q; Double membrane filtration; Immunoadsorption; Kidney transplantation.

Fig. 1

Depicted are the serum creatinine courses of the C1q-DSA-positive ABMR cases. “Treatment” refers to combined DFPP + IA treatments; “Σ” depicts total number of treatments in the respective treatment cycle. The arrows indicate allograft biopsies taken at respective days after transplantation.

Fig. 2

a Depicted are the absolute alterations of the respective molecules before and after a single DFPP + IA treatment. Index measurements (“before”) are normalized to 100%. b Total serum C1q levels before and after DFPP + IA treatments on seven consecutive treatment days. These data derive from patients “early 1” and “late 1.” The dashed lines mark the lower and upper border of normal C1q values. All data are presented as median + IQR. *** p < 0.001; **** p < 0.0001.