THROMBOTIC MICROANGIOPATHY AFTER KIDNEY TRANSPLANTATION: A RETROSPECTIVE COHORT STUDY

Thrombotic microangiopathy (TMA) is a severe condition involving microthrombi formation, platelet consumption, hemolytic anemia, and tissue ischemia. The kidney is particularly vulnerable due to the fragility of the glomerular endothelium, making TMA a major cause of graft dysfunction after kidney transplantation. It may present with hemolytic anemia, thrombocytopenia, and acute kidney injury, but is sometimes detected only on histopathology. Post-transplant TMAs are classified as de novo when no episodes of TMA were diagnosed previously or recurrent. Differentiating hemolytic uremic syndrome (aHUS) from secondary TMAs is essential because therapeutic strategies differ: secondary TMAs require correction of the underlying cause, whereas aHUS demands complement blockade with C5 inhibitors.

This was a retrospective, observational study based on medical record review, including all adult patients (≥18 years) who underwent kidney transplantation at the Hospital das Clínicas, School of Medicine, University of São Paulo, between 1987 and March 2024, and were diagnosed with post-transplant TMA. The overall follow-up was 39.1 months (IQR: 20.6–76.9), and post-TMA follow-up was 12.8 months (IQR: 1.7–43.6). Diagnosis was clinical (based on laboratory abnormalities and graft dysfunction) or histological (renal biopsy showing lesions compatible with TMA). Variables analyzed included demographic characteristics, TMA etiology, clinical manifestations, and patient and graft outcomes.

Among 4,752 kidney transplants, 92 patients (1.94%) developed TMA: 81 (88%) de novo and 11 (12%) recurrent. The mean creatinine at diagnosis was 4.39 mg/dL, with an estimated GFR of 12 mL/min/1.73m². The mean interval between transplant and TMA onset was 115.5 days, similar between groups. The average number of HLA mismatches was three. Maintenance therapy commonly included prednisone, tacrolimus, and mycophenolate, and induction therapy used thymoglobulin or anti–IL-2 receptor antibodies. The recurrent TMA group was younger (mean 31 vs. 43 years) and predominantly female (91% vs. 53%).

Regarding the underlying cause of chronic kidney disease, the most frequent diagnosis was glomerulonephritis (43%), followed by undetermined etiology (14%), hypertensive nephrosclerosis (10.8%), and aHUS (8.7%). All recurrent TMAs were due to aHUS, though only 8 patients (73%) had this diagnosed as the native disease. 2 cases were linked to malignant hypertension and one to snakebite-associated TMA.

For de novo TMA, the main associated factors were infection (23%), drug toxicity (22%), and rejection (19%), most commonly related to tacrolimus. 10 patients (12%) were diagnosed with aHUS without prior history. Other causes included ischemia–reperfusion injury (11%), indeterminate etiology (9%), and lupus with antiphospholipid syndrome (1%). Most TMAs (61%) had both clinical and histological findings (mean hemoglobin 7.4 g/dL, platelets 106,000/mm³, LDH 613 U/L, haptoglobin 10 mg/dL). In 38%, diagnosis was histologic only, mainly drug- or infection-related. 

Death-censored graft survival at 1 year was 54.5% for recurrent TMA and 60.6% for de novo TMA. The main causes of early graft loss (≤12 months after TMA) were rejection (50%), TMA itself (34%), and death (15%). 

The main factors associated with de novo TMA were infection, drugs, and rejection, while all recurrent cases were due to aHUS. 13 patients were diagnosed with post-transplant aHUS, underscoring its underdiagnosis and high recurrence. TMA had a major impact on graft survival, with a high rate of early graft loss. This abstract was first presented at the XIX Brazilian Congress of Transplantation in October 2025.