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ONCO-NEPHROLOGY
A GlomCon case-based discussion led by Dr. Raymond Hsu and Dr.Vighnesh Walavalkar from UCSF. Our Moderator’s Notes are derived from the live presentation.
By Dr. Jorge Castaneda
Key Points:
Patients treated with anti-VEGF tyrosine kinase inhibitors (such as cabozantinib ) can present in a variety of ways including ATN, AIN, TMA with endotheliosis and features of FSGS.
It is not uncommon to see endothelial and tubular damage simultaneously, in patients treated with tyrosine kinase inhibitors.
TMA can present only as “microangiopathy” with evidence of endothelial damage, but without thrombi (endotheliosis).
TMA can be renal limited. References: Jhaveri KD et al. KI Reports 2017; Launay-Vacher V. Annals Onc 2015
Sorafenib (also an anti-VEGF tyrosine kinase inhibitor) can be associated with HTN, FSGS, interstitial nephritis and hypophosphatemia.
In some cases, the tyrosine kinase inhibitors can be continued, depending on the progression of proteinuria.
Checkpoint inhibitors such as CTLA-4 antagonists (ipilimumab) and PD-1 inhibitors (pembrolimumab, nivolumab) induce sustained T-cell activation.
Checkpoint inhibitors are a known cause of AIN, but ATN has been reported as well.
Other organs can be involved with immune checkpoint inhibitors, especially skin and GI tract.
Treatment is usually empiric steroids. Although routinely not performed, renal biopsy may have a role in differentiating ATN from AIN. References: Wanchoo R. Am J Nephrol, 2017; Cortazar, KI 2016; Izzedine. CKJ 2019
Lenalinomide can be associated with acute T-cell mediated rejection.
Lenalidomide can also be associated with AKI, Fanconi syndrome and AIN. References: Walavalkar V. Transpl Proc, 2018
There are 2 types of Drug induced TMA (DITMA): A: Toxic Reaction: Direct cellular damage (e.g. gemcitabine, mitomycin, VEGF inhibitors, CNI, proteasome inhibitors). B: Immunological: Drug dependent antibodies (e.g. quinine, ticlopidine, gemcitabine, proteasome inhibitors).
Drug induced TMA does usually not present as classic TMA on biopsy, but rather primarily as an endotheliosis pattern.
If TMA is immune mediated, PLEX can be considered (opinion based).
Eculizumab has been used in case reports. References: Reese J, Am J Hematol,2015; Al Nouri et al 2015