37th Congress of the Italian Transplantation SocietyRenal transplantationEverolimus, Cyclosporine, and Thrombotic Microangiopathy: Clinical Role and Preventive Tools in Renal Transplantation
Section snippets
Materials and Methods
We analyzed 350 renal graft biopsy specimens gathered from 1998 to 2012 in 496 renal graft recipients (excluding kidney/pancreas, kidney/liver allografts, and primary nonfunction). Patients provided written informed consent before graft biopsy; the biopsy was indicated on clinical grounds (worsening renal function and/or proteinuria, signs of hemolitic anemia such as lactate dehydrogenase elevation, without other explanation). No protocol biopsies were performed.
In each patient with
Results
Thirty-six cases of TMA were found in 350 renal biopsy specimens in a population of 496 patients receiving a renal allograft. Prevalence was 7.3% (36 of 496). TMA that was not drug related (n = 19) included AMR (n = 11), viral infection (cytomegalovirus, human immunodeficiency virus) (n = 5), vasculitis (n = 1), systemic lupus erythematosus (n = 1), and recurrent atypical HUS (n = 1); drug-related TMA was found in 3.4% of patients (n = 17). Statistical analysis found no significant differences
Discussion
The goal of this study was to investigate the role of IS drugs in posttransplant TMA. We selected a TMA population not influenced by classical risk factors (eg, AMR, viral infections, vasculitides, systemic lupus erythematosus, recurrence of atypical HUS), in whom the role of the antirejection medication appeared predominant. However, we could not exclude the possible presence of underlying causes unknown at the time of onset.
According to the literature, drug-induced HUS represents 13% of all
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Cited by (22)
“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy
2024, Kidney International ReportsManagement of the kidney transplant patient with Cancer: Report from a Multidisciplinary Consensus Conference
2021, Transplantation ReviewsCitation Excerpt :Thrombotic microangiopathy [66] is a further rare, but typical adverse event of anti-angiogenic agents. In KTRs, CNI and mTORi are regularly used, and they might enhance the risk of thrombotic microangiopathy [67]. Therefore, proteinuria and early signs of thrombotic microangiopathy (anemia, lowering platelet count and aptoglobin levels) have to be carefully evaluated in these patients.
De novo thrombotic microangiopathy after kidney transplantation
2018, Transplantation ReviewsCitation Excerpt :Interestingly, not only were the CNI and the m-TOR inhibitor levels higher in the TMA group compared to those who did not develop this complication, the sum of concentrations of these two drugs was also higher in the former group (cyclosporine + everolimus: 15.2 ± 6.3 ng/dL in those with TMA vs 10.7 ± 2.1 ng/dL in those without TMA, and tacrolimus + everolimus: 21.1 ± 11.3 ng/dL in those with TMA vs 9.6 ± 1.3 ng/dL in those without TMA. Endothelial damage by CNI, in setting of mTOR inhibitor related impediment to repair of endothelial injury is postulated as the reason for this additive risk [32,35,36]. Based on these studies, we recommend caution with use of combination of these two classes of medications in the early post-transplant period when higher therapeutic levels are desirable, or in the presence of other risk factors for endothelial injury, for example presence of mutations in complement regulatory genes [19].
Secondary thrombotic microangiopathy and eculizumab: A reasonable therapeutic option
2017, NefrologiaCitation Excerpt :The mTOR inhibitors enhance post-transplant TMA by inhibiting VEGF synthesis by podocytes, enhancing endothelial damage and reducing endothelial regeneration capacity. The risk of SOT-TMA increases significantly when associated with both drugs.92,98–100 Management of SOT-TMA is not well established.
Use of Eculizumab in Transplant-Associated Thrombotic Microangiopathy in a Patient With Polycystic Kidney Disease Immediately Post–Kidney Transplant: A Case Report
2020, Kidney MedicineCitation Excerpt :Calcineurin inhibitors (CNIs) are frequently implicated in transplant-associated TMA, especially in the early period (3-6 months) after transplantation.3,4 Mammalian target of rapamycin inhibitors have also been associated with TMA and only belatacept (cytotoxic T lymphocyte antigen 4–immunoglobulin fusion protein that inhibits T-cell function) exists as an alternative to these agents.5,6 Withdrawal of CNI treatment alone may not be sufficient to fully reverse the adverse effects of the alternative pathway of complement activation associated with this condition.2,3
Onconephrology: Mitigation of renal injury in chemotherapy administration
2024, Current Opinion in Nephrology and Hypertension