TY - JOUR
T1 - Onconephrology and Thrombotic Microangiopathy
T2 - Looking Beyond the Horizon
AU - Gudsoorkar, Prakash
AU - Abudayyeh, Ala
AU - Tchakarov, Amanda
AU - Hanna, Ramy
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2022/11
Y1 - 2022/11
N2 - Thrombotic microangiopathies (TMAs) represent a complex interaction of endothelial and podocyte biology, nephron physiology, complement genetics, and oncologic therapies with host immunology. The complexity of various factors, such as molecular causes, genetic expressions, and immune system mimicking, along with incomplete penetrance, make it difficult to find a straightforward solution. As a result, there may be variations in diagnosis, study, and treatment approaches, and achieving a consensus can be challenging. Here, we review the molecular biology, pharmacology, immunology, molecular genetics, and pathology of the various TMA syndromes in the setting of cancer. Controversies in etiology, nomenclature, and points requiring further clinical, translational, and bench research are discussed. Complement-mediated TMAs, chemotherapy drug–mediated TMAs, TMAs in monoclonal gammopathy, and other TMAs central to onconephrology practice are reviewed in detail. In addition, established and emerging therapies within the US Food and Drug Administration pipeline subsequently are discussed. Finally, a comprehensive review of critical areas of onconephrology clinical practice is presented as practical value to the clinical practitioner and seeds of investigation to be sown among the community of atypical hemolytic uremic syndrome researchers.
AB - Thrombotic microangiopathies (TMAs) represent a complex interaction of endothelial and podocyte biology, nephron physiology, complement genetics, and oncologic therapies with host immunology. The complexity of various factors, such as molecular causes, genetic expressions, and immune system mimicking, along with incomplete penetrance, make it difficult to find a straightforward solution. As a result, there may be variations in diagnosis, study, and treatment approaches, and achieving a consensus can be challenging. Here, we review the molecular biology, pharmacology, immunology, molecular genetics, and pathology of the various TMA syndromes in the setting of cancer. Controversies in etiology, nomenclature, and points requiring further clinical, translational, and bench research are discussed. Complement-mediated TMAs, chemotherapy drug–mediated TMAs, TMAs in monoclonal gammopathy, and other TMAs central to onconephrology practice are reviewed in detail. In addition, established and emerging therapies within the US Food and Drug Administration pipeline subsequently are discussed. Finally, a comprehensive review of critical areas of onconephrology clinical practice is presented as practical value to the clinical practitioner and seeds of investigation to be sown among the community of atypical hemolytic uremic syndrome researchers.
KW - allogenic stem cell transplant (ASCT)
KW - biomarkers
KW - conventional chemotherapy
KW - targeted therapies
KW - Thrombotic microangiopathy (TMA)
KW - vascular endothelial growth factor inhibitor (VEGFi)
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U2 - 10.1016/j.semnephrol.2023.151345
DO - 10.1016/j.semnephrol.2023.151345
M3 - Review article
C2 - 37196461
AN - SCOPUS:85159935466
SN - 0270-9295
VL - 42
JO - Seminars in Nephrology
JF - Seminars in Nephrology
IS - 6
M1 - 151345
ER -