Abstract: PUB306
Delayed Presentation of Primary Podocytopathy and Membranoproliferative Glomerulonephritis (MPGN) Pattern of Injury Secondary to Pembrolizumab and Lenvatinib Use
Session Information
Category: Onconephrology
- 1700 Onconephrology
Authors
- Surapaneni, Anish, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Konda, Raghunandan, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Rosenblum, Frida, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Rizk, Dana V., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Rajasekaran, Arun, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Gandhi, Mamatha, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
Introduction
Immune checkpoint inhibitors (ICPI) like Pembrolizumab have transformed cancer therapy by enhancing T-cell responses via PD-1 inhibition but are increasingly linked to immune-related adverse events including kidney toxicity. Lenvatinib, a tyrosine kinase inhibitor (TKI) acting on VEGFR, FGFR, and PDGFR, is also linked with nephrotoxicity, mainly via endothelial glomerular injury. Early recognition and tailored management of ICPI and TKI induced kidney dysfunction are essential to preserve kidney function while maintaining cancer control.
Case Description
A 64-year-old male with hypertension, diabetes, and CKD 3b in the setting of metastatic renal cell carcinoma s/p radical nephrectomy with recurrence, with subsequent treatment with Pembrolizumab and Lenvatinib for 4 years, presented with non-oliguric AKI and nephrotic syndrome. Labs included SCr 2.5 mg/dL (baseline 2.0), serum albumin 1.9 g/dL, and UPCR 5.6 g/g. Urinalysis showed no acanthocytes. Comprehensive GN serological workup was negative. Kidney biopsy: LM showed 25 glomeruli with diffuse segmental sclerosis, double-contoured basement membranes, and hyaline microthrombi. There were no crescents or endocapillary proliferation. IF showed low-grade granular staining along the capillary walls and mesangium for IgM, IgA, C3, trace C1q, and light chains. EM revealed diffuse podocyte foot process effacement in non-sclerotic and sclerotic glomeruli without deposits. A diagnosis of diffuse podocytopathy with FSGS and MPGN pattern of kidney injury likely in the setting of Pembrolizumab and Lenvatinib was made. These medications were held; high-dose glucocorticoids with taper was initiated leading to resolution of AKI, normalization of serum albumin, and complete remission of proteinuria.
Discussion
Our case highlights delayed presentation of diffuse podocytopathy with FSGS and MPGN likely in the setting of Pembrolizumab and Lenvatinib use after 4 years of being on therapy. The exact etiology for delayed podocytopathic and glomerular endothelial involvement of these medications is unclear. Holding the offending agents and starting glucocorticoids led to complete resolution of nephrosis, suggesting immunosuppression may not be necessary in such cases. Individualized treatment approach for these cases is warranted.