The impact of the type of post-transplant thrombotic microangiopathy on graft and patient outcomes

Introduction: Post-transplant thrombotic microangiopathy (PT-TMA) affects 0.8–15% of kidney transplant (KT) recipients and is associated with poor graft and patient outcomes. The pathogenesis of PT-TMA is multifactorial, with the most common causes being calcineurin inhibitor (CNI) toxicity, ischemia-reperfusion injury (IRI), antibody-mediated rejection (AMR), autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome (APS), etc.), infections, and atypical hemolytic uremic syndrome (aHUS). The aim of our study was to compare the graft and patient survival in different types of PT-TMA.
Methods: A retrospective cohort study included 84 patients with PT-TMA diagnosed based on graft biopsy performed between January 2012 and December 2023. Patients were divided into 6 groups depending on the cause of PT-TMA: 1 – CNI toxicity (15 patients), 2 – aHUS (17 patients), 3 – AMR (22 patients), 4 – APS/infections (9 patients), 5 – IRI (11 patients), 6 – unknown cause (10 patients). Demographic and laboratory data (serum creatinine (SCr), daily proteinuria, hemoglobin (Hb), platelets count, LDH) at the time of diagnostic biopsy, 3-year graft survival and 3-year patient survival were assessed. Statistical analysis was performed using the SPSS STATISTIC 23 (Mediana (Me) [IQR 25%; 75%], Kaplan–Meier estimator).
Results: Patients in the selected groups did not differ significantly by gender, SCr, daily proteinuria, Hb, platelets count and LDH (p > 0.5). Patients with aHUS were younger (38 [28; 43] years) than patients with AMR (46 [41; 52] years, p = 0.005), IRI (54 [46; 60] years, p = 0.0001) and unknown TMA (49 [34; 56] years, p = 0.049). The time of TMA development after KT in the IRI group was significantly shorter (1.0 [0.4; 1.8] months) than in CNI toxicity (11 [1; 52] months, p = 0.0001), aHUS (6 [0.7; 42] months, p = 0.014), AMR (7 [0.6; 39] months, p = 0.046) and unknown TMA (7 [0.9; 22] months, p = 0.01). The worst 3-year graft survivals were observed in the APS/infection group (0%), aHUS (9%), and IRI (17%). Higher graft survivals were in the AMR (41%), unknown TMA (45%), and CNI toxicity (48%). Statistical differences were observed in the CNI toxicity and aHUS (p = 0.02) and CNI toxicity and APS (p = 0.047). The lowest 3-year patient survival rate was in APS (46%) and aHUS (47%). Patient survival was 65% in the CNI toxicity group. All patients with AMR, IRI and unknown TMA were alive by the end of the third year of follow-up. Significant differences in patient survival were found in aHUS and AMR (p = 0.047), APS and AMR (p = 0.007), and APS and unknown TMA (p = 0.04).

Conclusion: The type of PT-TMA significantly impacts graft and patient survival. The lowest graft and patient survival rates were observed in aHUS and APS/infection groups. Graft survival was low, but patient survival was 100% by the end of the third year of follow-up in IRI group. These differences highlight the importance of systemic and extrarenal TMA manifestations, typical for patients with aHUS, APS and infections, in determining long-term patient prognosis.