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Kidney Week

Abstract: TH-PO145

Immune-Complex Glomerulonephritis Following PD-1 and PD-L1 Therapy in Renal Cell Carcinoma

Session Information

Category: Trainee Case Report

  • 103 AKI: Mechanisms

Authors

  • Leger, Kathleen, Yale University School of Medicine, New Haven, Connecticut, United States
  • Cavanaugh, Corey J., Yale University, New Haven, Connecticut, United States
  • Shirali, Anushree C., Yale University, New Haven, Connecticut, United States
Introduction

Inhibition of the Programmed cell death-1 (PD-1) pathway is associated with interstitial nephritis. Vascular endothelial growth factor (VEGF) inhibition via receptor tyrosine kinase blockade (RTKi) is associated with hypertension (HTN), proteinuria, thrombotic microangiopathy (TMA), and podocytopathies. Here we describe the development of Immune-complex glomerulonephritis (ICGN) in a patient who was treated with PD-L1 inhibitor, atezolizumab, and PD-1 inhibitor, nivolumab.

Case Description

A 49-year-old male with metastatic RCC and nephrectomy presented with worsening HTN and found with acute kidney injury (AKI). Initial treatment for RCC prior included bevacizumab (VEGF), pegylated interferon, and atezolizumab (anti-PD-L1). Following cycle 4, bevacizumab was held due to HTN and new proteinuria of 1.9 g/g. Despite this, proteinuria worsened to 5.2g/g and treatment changed to sunitinib and nivolumab. Following the initiation of this new regimen, he was admitted for AKI (with serum creatinine (SCr) increasing from 1.6 mg/dl to 2.6mg/dl), proteinuria of 9.2g/g, and a serum albumin that fell to 1.6g/dl from 3g/dl. Renal biopsy showed no interstitial infiltrate but one glomerulus displayed thickened. Electron microscopy showed segmental subepithelial, subendothelial, and numerous mesangial deposits with global foot process effacement. Immunofluorescence could not be obtained. These findings were consistent with an ICGN. Prednisone and a loop diuretic were initiated. Nivolumab was held and sunitinib was continued. At 1 month follow up, his NS improved along with serum albumin that rose to 2.3g/dl. Unfortunately, his RCC continued to progress and he subsequently passed away.

Discussion

PD-1 inhibition has become a cornerstone of many immunotherapeutic regimens for various malignancies. We describe a case of progressive proteinuria, AKI, and subsequent NS with biopsy proven ICGN following PD-L1 and PD-1 inhibition that responded to corticosteroids. This case describes a novel case of ICGN, seen rarely with anti-VEGF therapy, now seen with PD-L1 and PD-1 inhibition.