TY - JOUR
T1 - Thrombotic Microangiopathy After Kidney Transplantation
T2 - Insights Into Genetic Etiology and Clinical Outcomes
AU - Merzkani, Massini
AU - Chann Wai Lynn, Nyein
AU - Flores, Karen
AU - Rajashekar, Gaurav
AU - Progar, Kristin
AU - Santos, Rowena Delos
AU - Atkinson, John P.
AU - Brennan, Daniel C.
AU - Java, Anuja
N1 - Publisher Copyright:
© 2025
PY - 2025/4
Y1 - 2025/4
N2 - Introduction: Thrombotic microangiopathy (TMA), characterized by small-vessel thrombosis caused by endothelial injury, presents significant diagnostic and treatment challenges in kidney transplantation. Methods: To investigate the factors associated with posttransplant TMA, we conducted a retrospective study of 3535 kidney transplant recipients at our center from 2008 to 2023. Results: Sixty-eight patients were diagnosed with TMA, and 93% (63 of 68) underwent genetic testing. Patients were categorized into 3 groups based on the TMA etiology. Group 1 (n = 42, 62%) included patients with complement-mediated TMA associated with genetic or acquired complement abnormalities. These patients were younger and had a higher incidence of hypertension (HTN) or preeclampsia as the causes of end-stage kidney disease (ESKD). Notably, 33% of patients developed recurrent TMA, and approximately 78% of those with recurrent TMA lost their allografts. Group 2 (n = 14, 21%) had TMA associated with calcineurin inhibitors (CNIs) or ischemia-reperfusion injury (IRI), showing longer cold ischemia times (CITs) (19.9 ± 8.7 hours vs. 10.7 ± 8.9 hours; P = 0.0001) and a higher rate of delayed graft function (DGF) (43% vs. 13%, P = 0.0008) than the controls. Group 3 (n = 12, 17%) had TMA from diverse causes (infections or autoimmune disorders) and exhibited a poor response to anticomplement therapy. No genetic variants were identified in this group. Conclusion: Our findings underscore the need for comprehensive pre and posttransplantation genetic testing to predict and manage the risk of TMA and prevent graft loss. CNIs may exacerbate the risk of posttransplant TMA in the presence of other complement-activating factors. Our study also highlights the importance of personalized strategies and early interventions based on the functional assessment of variants of uncertain significance (VUS).
AB - Introduction: Thrombotic microangiopathy (TMA), characterized by small-vessel thrombosis caused by endothelial injury, presents significant diagnostic and treatment challenges in kidney transplantation. Methods: To investigate the factors associated with posttransplant TMA, we conducted a retrospective study of 3535 kidney transplant recipients at our center from 2008 to 2023. Results: Sixty-eight patients were diagnosed with TMA, and 93% (63 of 68) underwent genetic testing. Patients were categorized into 3 groups based on the TMA etiology. Group 1 (n = 42, 62%) included patients with complement-mediated TMA associated with genetic or acquired complement abnormalities. These patients were younger and had a higher incidence of hypertension (HTN) or preeclampsia as the causes of end-stage kidney disease (ESKD). Notably, 33% of patients developed recurrent TMA, and approximately 78% of those with recurrent TMA lost their allografts. Group 2 (n = 14, 21%) had TMA associated with calcineurin inhibitors (CNIs) or ischemia-reperfusion injury (IRI), showing longer cold ischemia times (CITs) (19.9 ± 8.7 hours vs. 10.7 ± 8.9 hours; P = 0.0001) and a higher rate of delayed graft function (DGF) (43% vs. 13%, P = 0.0008) than the controls. Group 3 (n = 12, 17%) had TMA from diverse causes (infections or autoimmune disorders) and exhibited a poor response to anticomplement therapy. No genetic variants were identified in this group. Conclusion: Our findings underscore the need for comprehensive pre and posttransplantation genetic testing to predict and manage the risk of TMA and prevent graft loss. CNIs may exacerbate the risk of posttransplant TMA in the presence of other complement-activating factors. Our study also highlights the importance of personalized strategies and early interventions based on the functional assessment of variants of uncertain significance (VUS).
KW - antibody-mediated rejection
KW - calcineurin inhibitors
KW - complement
KW - genetics
KW - kidney transplantation
KW - thrombotic microangiopathy
UR - http://www.scopus.com/inward/record.url?scp=105001078487&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2025.01.026
DO - 10.1016/j.ekir.2025.01.026
M3 - Article
AN - SCOPUS:105001078487
SN - 2468-0249
VL - 10
SP - 1152
EP - 1162
JO - Kidney International Reports
JF - Kidney International Reports
IS - 4
ER -