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The presence of specific antibodies against human leukocyte antigen (HLA-DSA) is considered the main cause of antibody-mediated rejection (ABMR). However there is a subgroup of patients with ABMR histological characteristics but without detectable HLA-DSA (20%). We present the clinical case of a hypersensitized and retransplanted patient with early AMR manifested as severe thrombotic microangiopathy (TMA) due to non-HLA antibodies (non-HLA Ab)
Clinical Case
50-year-old patient, history of IgA Nephropathy at age 18, G4P2A2, preeclampsia and 2 previous transplants (Tx), both graft loss due to late ABMR (2003-2011 and 2011 to 2023). Since 2018 with monthly Tocilizumab. Receives third Tx deceased donor on March 30, 2023. Historical PRA >85% and current 47%. CKD-EPI 15 ml/min, residual diuresis 2500 cc. Three weeks before the Tx he had contact with his daughter with confirmed covid-19, the patient developed concomitant diarrhea without confirmation of covid-19. Received a optimal donor, Cold ischemia time 17 hours, cross match by flow cytometry (FCXM) , and current HLA-DSA were negative, but has historical DSA A2 (serum from 2011 with 2900 MFI ). Covid-19 was negative donor and recipient. Induction Solumedrol, Thymoglobulin and IVIG. Maintenance Tacrolimus , Myfortic, steroids and intravenous Immunoglobulin(IVIg)2gr per kg.
No surgical incidents, optimal perfusion upon declamping. Immediate Doppler echo: perfused kidney, IR 0.54, volume 150 cm , with diuresis 200-300 cc/h, graft dysfunction (creatinine serum 2.5mg%).At 36 hrs after Tx she presents a drop in Hemoglobin (11.4 to 7.5) and platelets (145,000 to 38,000), LDH 500. Doppler reveals a transplant kidney perfused to proximal but with severe decrease in distal perfusion, IR 0.88 and a large increase in volume to 370 cc. Directed search show blood smear schistocytes and low haptoglobin. On day 5 platelets reach 25,000 and Hbo at 6.6. Plasmapheresis (Plex) was started 36 hrs after Tx achieving remission of the condition after 10 days. She received 14 Plex ,Solumedrol, Rituximab (1gr) and IVIg (2g per kg)again , and then Tocilizumab (600mg) was restarted on day 14 . She presented respiratory failure on day 3 with clinical picture and images suggestive of covid-19 who responded easily to ventilatory support therapies with CNAF. Respiratory film array and broqueoalveloar lavage finding
did not demonstrate infectious etiology. Post-transplant study FCXM and HLA-DSA were negative. Non-HLA Ab study was positive for ATR1 (+) 12.3 (range >10) and Endothelin type A (+) 2.9 (range >2). Early candesartan is added. Non-HLA Ab control at 21 days was negative after treatment. Given the high risk of complications, the renal biopsy was deferred, which was performed after 34 days and showed mild PTC1, few PMN and mild Interstitial tubulitis, without qualifying for current rejection, C4d negative. Protocol biopsy in the 3rd month without ABMR, mild CNI toxicity. Currently, 6 months post Tx, renal function was stable with creatinine of 1.6 mg% without proteinuria.
This clinical case of a TMA phenotype associated with Non-HLA Ab and clinical ABMR; shows the relevance of non-HLA antibodies in early graft rejection, especially in sensitized, retransplanted patients and with a history of preeclampsia.
The evaluation of Non- HLA (AT1R-Ab and ETAR-Ab) and HLA-DSA could provide a complementary and integrated assessment of immunological risk, guiding an individual therapeutic immunosupression.