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. 2024 Jul 30;9(10):2927-2936.
doi: 10.1016/j.ekir.2024.07.024. eCollection 2024 Oct.

Imlifidase in Highly Sensitized Kidney Transplant Recipients With a Positive Crossmatch Against a Deceased Donor

Nassim Kamar  1 , Dominique Bertrand  2 , Sophie Caillard  3 , Danièle Pievani  4 , Marie Joelle Apithy  5 , Nicolas Congy-Jolivet  6   7 , Bertrand Chauveau  8 , Fabienne Farce  9 , Arnaud François  10 , Audrey Delas  11 , Jérôme Olagne  12 , Cédric Usureau  13 , Jean-Luc Taupin  13 , Gwenda Line Guidicelli  14 , Lionel Couzi  15
Affiliations

Imlifidase in Highly Sensitized Kidney Transplant Recipients With a Positive Crossmatch Against a Deceased Donor

Nassim Kamar et al. Kidney Int Rep. .

Abstract

Introduction: Imlifidase is authorized for desensitization of highly sensitized adult kidney transplant candidates with a positive crossmatch (XM) against a deceased donor. Here, we report on the results for the first 9 patients transplanted in this context who had at least 3 months of follow-up.

Methods: The eligibility criteria were as follows: calculated panel reactive antibodies (cPRA) ³ 98%, ³ 3 years on the waiting list, immunodominant donor-specific antibodies (DSAs) with mean fluorescence intensity (MFI) > 6000 (and < 5000 at 1:10 dilution) and a negative post-imlifidase complement-dependent cytotoxic XM (CDCXM).

Results: All 9 patients had been on dialysis for an average of 123 ± 41 months, with cPRA at 99% (n = 2) or 100% (n = 7). At transplantation, the mean number of DSAs was 4.3 ± 1.4. The median immunodominant DSA MFI was 9153 (6430-16,980). Flow cytometry XM (FCXM) and CDCXM before imlifidase were positive in 9 and 2 patients, respectively. After 1 injection of imlifidase, all were negative. Patients received polyclonal antibodies, i.v. Igs (IVIg), rituximab, tacrolimus, and mycophenolate. Five patients had a DSA rebound within the first 14 days: 2 had concomitant clinical antibody-mediated rejection (ABMR), 2 had subclinical ABMR, and 1 had isolated positive C4d staining. No ABMR was observed in patients without rebound. Chronic Kidney Disease-Epidemiology Collaboration formula estimated glomerular filtration rate (eGFR) was 56 ± 22 ml/min per 1.73 m2 at the last follow-up (7 ± 2.8 months). No graft loss or death were observed. Four patients developed at least 1 infection.

Conclusion: These real-life data demonstrate that the use of imlifidase to desensitize highly sensitized patients can have an acceptable short-term efficacy and safety profile in selected patients.

Keywords: highly sensitized patients; imlifidase; kidney transplantation; positive crossmatch.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Outcome of immunodominant donor-specific antibodies (DSAs) after transplantation. (a) In blue, class I and class II immunodominant DSAs without posttransplant rebound. (b) In red, class I and class II immunodominant DSAs with posttransplant rebound. iDSA, immunodominant DSA; MFI, mean florescent intensity.
Figure 2
Figure 2
Outcome of donor-specific antibodies (DSAs) after transplantation. (a) In blue, sum of class I and class II DSAs, (b) class I DSAs, and (c) class II DSAs in patients without posttransplant rebound. (d) In red, sum of class I and class II DSAs, (e) class I DSAs, and (f) class II DSAs in patients with posttransplantation rebound.
Figure 3
Figure 3
Posttransplant evolution of repeated and unrepeated anti-HLA DSA mismatches. DSA, donor-specific antibody; HLA, human leukocyte antigen.
Figure 4
Figure 4
Histological features at days 7 to 10 and month 3 in patients with and without posttransplant rebound. Panel a, tubulitis (t). Panel b, inflammation (i). Panel c, glomerulitis (g). Panel d, peritubular capillaritis (ptc). Panel e, C4d staining.
Figure 5
Figure 5
Outcome of (a) serum creatinine level and (b) CKD EPI estimated glomerular filtration rate, after transplantation. CKD EPI, chronic kidney disease epidemiology collaboration formula.
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References

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