ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO517

Vacuolated Podocytopathy: A Novel Injury with the Use of BRAF Inhibitors

Session Information

  • Trainee Case Reports - I
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Virmani, Sarthak, Yale School of Medicine, New Haven, Connecticut, United States
  • Shirali, Anushree C., Yale University, New Haven, Connecticut, United States
Introduction

With expanded use of BRAF inhibitors, nephrotoxicities including acute interstitial nephritis (AIN) and nephrotic syndrome (NS) have been described in recent literature. We present a novel case of vacuolated podocytopathy with sub-nephrotic range proteinuria associated with BRAF inhibition.

Case Description

A 64-year-old woman with non-small-cell lung cancer on dual BRAF/MEK inhibition with Vemurafenib and Trametinib, was referred for AKI evaluation. Her serum creatinine (SCr) was 2.1 mg/dL, increased from 1.0 mg/dL 2 months prior. Urine protein/creatinine ratio was between 0.4 – 0.7. Urinalysis was otherwise non-contributory. BRAF inhibition was held due to presumed AIN, but renal function only improved to 1.4 mg/dL. Treatment was restarted due to lack of therapy options with increase in SCr to 2.0 mg/dL. A renal biopsy was performed for definitive diagnosis. Pathology surprisingly showed a minimal interstitial infiltrate but extensive podocyte injury with cytoplasmic vacuolization and nearly global foot process effacement (FPE) was seen on electron microscopy. Given stable renal function, treatment was continued. Her SCr remained around 2.0-2.2 mg/dL and proteinuria remained < 1g until her death from septic shock few months later.

Discussion

BRAF inhibitors are linked with AIN and NS with diffuse FPE. We describe a novel finding of podocyte vacuolization and FPE with sub-nephrotic proteinuria. We recommend renal biopsy for patients on BRAF inhibitors with AKI of undetermined etiology to allow precise identification of the renal lesion. Our patient continued on BRAF inhibitors with stable CKD and proteinuria, suggesting that drug withdrawal is not necessary for all patients, particularly those with limited treatment options.

EM with podocyte vacuolization (arrow) and FPE