Wednesday, November 13, 2019

Topic Discussion: Interferons and kidney disease

Interferons usually have been linked with kidney damage with forms of podocytopathies. CJASN paper from 2010 from CUMC described these lesions. Collapsing FSGS may occur after treatment with IFN-alpha, -beta, or -gamma and is typically accompanied by the ultrastructural finding of endothelial tubuloreticular inclusions.
Following that series of 11 patients showing Collapsing GN, few cases reports were published in 2016 showing FSGS as well. Another large series by Markowitz et al in 2015 of 32 patients also showed podocytopathies but this time also MCD and FSGS along with collapsing GN. The MCD patients had complete and partial remission but the FSGS and collapsing GN had <50% complete or partial remissions.

But the most common lesion that is hidden in the heme literature is TMA but many being renal limited. There are now over 80 cases described of TMA , AKI and HTN related to interferons. Outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease (CKD) in 28 (42%) and fatality in 12 patients (18%). (10) Treatment with corticosteroids, plasma exchange and rituximab resulted in durable responses.

In an elegant experiment by a group published in 2016 in Blood showed that type 1 interferon can induced TMA. They showed that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA with interferon. They then showed that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor. Together their clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. So, this experiment showed that from bedside to bench the clear relationship of interferon and TMA development.
So in summary, the renal lesions seen with Interferon should really be TMA, and podocytopathies such as FSGS, collapsing GN and MCD.

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