Early TMA more frequently observed in the presence of anti-HLA class-II antibodies, preformed DSA and induction with thymoglobulin were associated with acute ABMR and bacterial infections and had an excellent prognosis

Early TMA more frequently observed in the presence of anti-HLA class-II antibodies, preformed DSA and induction with thymoglobulin were associated with acute ABMR and bacterial infections and had an excellent prognosis. included death, graft function (defined by serum creatinine levels) and end-stage renal failure (chronic dialysis or new transplantation), new onset ABMR or/and TCMR and recurrence of TMA. Statistical analysis Continuous variables were offered as median (Interquartile range [IQR]). Non-parametric MannCWhitney-Wilcoxon test or KruskalCWallis test followed by Dunns test were utilized for comparisons. Categorical variables were offered as figures and percentage, and we used 2-test or Fisher test for univariate analysis. After a preliminary analysis of the timing of TMA during post-transplant management, it appeared that 3 unique situations could be observed. The first group was constituted by patients who developed TMA within the first 2?weeks after transplantation early (early TMA: eTMA). The second group was constituted by the unexpected TMA anytime during follow-up, starting after the second week following transplantation (Unexp-TMA). The third group was constituted of patients with failing graft [12] who presented with TMA (Fail-TMA) (Fig.?1). E 2012 For graft survival, only early and unexpected TMA groups were considered. Statistical analysis was conducted using GraphPad (version 8, Prism, San Diego.United State). The study was approved by the regional ethic committee (Espace de reflexion thique region Centre: research project no. 2017C003). Open in a separate window Fig. 1 TMA in kidney transplant recipients Results Baseline characteristics and incidence of TMA During the 2009C2021 period, 1644 patients experienced a kidney transplantation whereas 2925 patients who received a transplantation since 1985 were followed up in our center (total follow-up period: 20,293 patient-years (/1,000-PY)). During this period, graft loss occurred in 491 patients (renal replacement therapy: BPHUS2 (3)0 (0)2 (6)0 (0)0.33Infections32 (42)7 (29)16 (52)9 (41)0.24Bacteria17 (22)6 (25)6 (19)5 (23)0.93(without evidence of shiga toxin)4 (5)3 (13)0 (0)1 (5)0.96Other gram-negative bacilli7 (9)1 (4)3 (10)3 (14)0.48Streptococcus2 (3)2 E 2012 (8)0 (0)0 (0)0.17Staphylococcus1 (1)0 (0)0 (0)1 E 2012 (5)0.29Virus17 (22)1 (4)10 (32)6 (27)0.03Epstein-Barr virus9 (12)0 (0)6 (19)3 (14)0.06Cytomegalovirus9 (12)0 (0)5 (16)4 (18)0.06Other2 (3)1 (4)1 (3)0 (0)1.00Not documented3 (4)1 (4)2 (6)0 (0)0.78Pre-eclampsia1 (1)0 (0)1 (3)0 (0)1.00Malignant hypertension8 (103 (13)1 (3)4 (18)0.22Malignancies9 (12)1 (4)2 (6)6 (27)0.04Autoimmune diseases3 (4)0 (0)3 (10)0 (0)0.11CNI E 2012 toxicity, n (%)6 (8)2 (8)4 (13)0 (0)0.27Combination of CNI and mTOR inhibitor, n (%)4 (5)1 (4)3 (10)0 (0)0.45Conditions associated with other TMAs30 (39)13 (54)8 (26)9 (41)0.01Large hematoma9 (12)4 (17)4 (13)1 (5)0.45Folate deficiency19 (25)8 (33)3 (10)8 (36)0.04Vitamin B12 deficiency2 (3)1 (4)1 (3)0 (0)1.00 Open in a separate window TMA?Thrombotic microangiopathy, HUS?Hemolytic and uremic syndrome, CNI?Calcineurin inhibitors mTOR?Mammalian target of Rapamycin Most frequent causes of TMA in the 3 groupsAs shown in Table ?Table2,2, infections (29%), were the most common cause of TMA among patients with eTMA. Acute antibody-mediated rejection (ABMR) was diagnosed in 4 patients. Of notice, folate deficiency was present in 8 patients. Malignant hypertension was present in 13% of eTMA patients. Infections were the most frequent cause of unexp-TMAs (52%). Viral reactivation (EBV and CMV) was more frequent in unexp-TMA compared to eTMA and fail-TMA with 32%, 0% and 27%, respectively (p?=?0.03). CNI toxicity based on tacrolimus trough level above 12?ng/mL (8% of TMAs). Other frequent causes of TMA were ABMR (13%), aHUS (10%), auto-immune disease (10%) and shigatoxin-associated HUS (6%). Among patients with fail-TMA, acute ABMR and chronic active ABMR were present in 18% and 64% of patients, respectively. Infections (41% of fail-TMA patients, with EBV and CMV reactivations in 14 and 18%, respectively), malignancies (27% compared TFRC with 4% and 6% in eTMA and unexp-TMA, respectively, p?=?0.04) and malignant hypertension (18%) were commonly associated with TMA. Histology findings of patients with TMAOverall, 27 patients (35%) experienced a kidney biopsy (8 patients, 10 patients and 9 patients in the eTMA, unexp-TMA and fail-TMA groups, respectively) (Table S1). Capillary luminal narrowing, glomerular.