THROMBOTIC MICROANGIOPATHY AND KIDNEY TRANSPLANTATION (KT). A SINGLE CENTER EXPERIENCE.

Background:

TMA is a complication of KT involving elevated mortality and a poor prognosis.

Objective:

To report the features of patients with TMA and atypical Hemolytic Uremic Syndrome (aHUS) in pre transplant evaluation and post kidney transplantation in our hospital.

Retrospective review of medical records of patients who underwent KT and patients on Waiting Transplant List (WTL), between 1998 and 2023 in Fundacion Favaloro University Hospital.

During the mentioned period, we analyze different groups. We focused on patients who have received eculizumab treatment. See genetic studies table.

Group 1. Diagnosis of aHUS (positive genetic test) and eculizumab treatment during dialysis due to extrarenal complications of MAT. 4/5 patients received KT and continue with eculizumab treatment.  1/5 patient is on liver-kidney waiting transplant list (WTL). No relapses were reported.

Group 2. Diagnosis of aHUS on pre transplant evaluation, received prophylactic eculizumab started at KT. 3/3 patients continue receiving eculizumab post transplantation, no recurrence reported. Genetic test consisting in CFH risk haplotypes and CFH heterozygous variants. 

Group 3. Post renal transplantation TMA.

-TMA secondary to infection. 2 patients (bacteriemia and Covid pneumonia), they received eculizumab to stop TMA with favorable response, then it was discontinued.

-TMA secondary to rejection. Challenging indication of eculizumab due to abscense of genetic test prior to event: 2/3 patients with Antibody Mediated Rejection (AMR) and TMA, 1/3 ABO incompatible rejection.

-TMA secondary to calcineurin inhibitor. 1 patient who received a preemptive kidney transplant from related donor, and developed systemic TMA (lung, native and transplant kidneys, myocardium) and sudden death. Genetic study showed mutation on THBD gene and CFHR3 and CFHR1. 2 patients who resolved TMA with eculizumab treatment, 1 of them decided to discontinue.

Summary.

Between 1998 and 2023, 1,291 patients received a KT, 26 presented TMA (2.01%). 11/26 patients maintain graft function.

On pre eculizumab era, 6/13 lost their graft, 5/13 died, 2/13 maintain kidney function.

On post eculizimub era: 3/13 lost kidney graft, 1/13 died due to catastrophic systemic TMA, 9/13 maintain kidney function.

 17/26 Received tacrolimus (FK) + mycophenolate (MPA); 6/26 received FK + mTORi (mTOR inhibitors), 1/26 FK + azathioprine, 1/26 patient presented recurrence in the induction inmunosupression phase prior to FK start, 1/26 FK + Belatacept. In all cases, FK was suspended, and TMA persisted; 15/26 received plasma exchange (PE) and were refractory.

TMA and Belatacept.

Prior to Belatacept era 6/23 patients lost their graft.

In the Belatacept era: 17/23 switched to Belatacept and 2 patients lost their grafts because they decided to discontinue Eculizumab and Belatacept.

Pre Transplant Evaluation.

- 20/839 (2.38%) patients on WTL (waiting transplant list) have aHUS confirmed diagnosis. See table below.

Very early use of Eculizumab after exclusion of another TMA etiologies, favorably resolved graft survival and mortality in most cases of TMA post transplantation.

Switch to belatacept is safe in secondary TMA.

Pre-transplant screening allows to identify risk mutations; lead prophylactic therapy and quickly introduce of eculizumab in unexpected relapse.

Use of eculizumab as rescue therapy on humoral rejection should be considered. Secondary TMA are consisting with polymorphisms and risk haplotypes of genetic tests.