Desensitization protocol for highly sensitized kidney transplant candidate with cPRA 98% and DSA MFI >10,000 | tachyDx

2 Answers

Accepted Answer

This is one of the most challenging scenarios in transplant nephrology. At Manipal, we have treated 6 patients with cPRA > 95% in the past 3 years. Here is our approach:

1. Desensitization protocol for MFI > 10,000: We use a modified Johns Hopkins protocol:

Phase 1 (weeks 1-4): Bortezomib 1.3 mg/m2 (days 1, 4, 8, 11) x 2 cycles + dexamethasone 20mg + plasmapheresis x 6 sessions
Phase 2 (weeks 5-8): IVIG 2g/kg (divided over 2 days) + rituximab 375 mg/m2 x 1
Phase 3: Repeat DSA testing. If MFI drops below 5,000, proceed with transplant with desensitization protocol at time of surgery

Our success rate with this protocol: 4/6 patients achieved transplantable MFI levels.

2. Imlifidase (IdeS): This is a game-changer for exactly this scenario. IdeS cleaves all IgG within hours, achieving a temporary "negative crossmatch window." The Highdes trial showed that 92% of highly sensitized patients converted to a negative crossmatch within 24 hours.

However: IdeS is only approved in the EU. If available, I would use it as a rescue strategy if bortezomib + rituximab fails to reduce MFI below 5,000. The protocol: administer IdeS 0.25 mg/kg IV 6 hours before transplant surgery, then proceed with living donor transplant during the window.

3. MFI threshold: We accept a calculated crossmatch risk if:

Flow cytometry crossmatch is negative or weakly positive (MCS < 200)
DSA MFI < 5,000 for class I, < 3,000 for class II (especially DQ)
C1q binding assay is negative at the time of transplant

The DQ antibodies at MFI 6,300 are actually my biggest concern in this case. DQ DSA are the strongest predictor of antibody-mediated rejection recurrence, and they are the hardest to desensitize.

Dr. Ananya Ghosh· Nephrology· answered 6 Apr 2026

Dr. Ghosh, thank you for the detailed protocol. Sharing our KFSH experience for comparison:

We have been using IdeS since 2024 (approved in Saudi Arabia via emergency access pathway). Our results with 8 highly sensitized patients:

7/8 converted to negative crossmatch within 6 hours
6/8 underwent successful transplantation
1 patient had hyperacute rejection despite negative crossmatch (likely non-HLA antibodies)
1 patient had IdeS infusion reaction requiring ICU admission

Key learning: The crossmatch window after IdeS is approximately 7-10 days before IgG reconstitutes. You MUST have the living donor surgery team on standby before administering IdeS. Any delay beyond 24-48 hours risks losing the window.

Post-transplant after IdeS: We use a modified immunosuppression protocol:

Thymoglobulin induction (not basiliximab, as basiliximab is an IgG and gets cleaved by residual IdeS)
Tacrolimus + mycophenolate + steroids
Serial DSA monitoring weekly for 3 months
Protocol biopsies at 1, 3, and 6 months

Regarding the DQ7 antibody: I agree this is the most concerning. In our series, the 1 patient with hyperacute rejection had a pre-transplant DQ DSA MFI of 4,200 that we thought was "safe." I now consider DQ class II DSA above MFI 3,000 as a relative contraindication unless IdeS is available.