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Kidney Week

Abstract: PO1868

Treatment of PLA2R-Negative Membranous Nephropathy in the Setting of Immune Checkpoint Inhibitor and Renal Cell Carcinoma

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Reddy, Vikas D., The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Kala, Jaya, The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Msaouel, Pavlos S., The University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, United States
  • Glass, William F., The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Mamlouk, Omar, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Abudayyeh, Ala, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Lin, Jamie S., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Introduction

Systemic therapy of renal cell cancer (RCC) has undergone major changes over the past decade with the development of targeted therapies such as tyrosine kinase inhibitors (TKIs) and biologic therapies such as immune checkpoint inhibitors (ICIs). Familiarization of the unique nephrotoxicity associated with each treatment is necessary to optimize renal outcomes and cancer care.

Case Description

57-year-old male with metastatic RCC s/p left nephrectomy progressed after being treated for 16 weeks with the TKI axitinib in combination with pembrolizumab, an ICI targeting PD-1. He subsequently progressed after a 14-week course with second-line cabozatinib (TKI) and was initiated on third-line levatinib (TKI) plus everolimus (mTOR inhibitor) two months prior to presenting with severe diarrhea. Labs were notable for creatinine (Cr) of 2.28 mg/dL (baseline 0.96 mg/dL). CT revealed suspicion for colitis and decreased tumor size of his metastatic disease. Further work-up revealed: 2.87 g on 24 h urine protein, negative anti-GBM and ANCA antibodies, and normal complements. Renal ultrasound showed a hypertrophic right kidney measuring 14 cm in length without obstruction. Due to the broad AKI differential, steroids were empirically started for possible immune-mediated disease, and biopsy was obtained. Pathology revealed membranous nephropathy (MN) with mesangial deposits, PLA2R and THSD7A were negative. With worsening renal function (Cr 3.87 mg/dL) and risk for progression to dialysis, treatment with rituximab (1 g IV D1 and D14) was initiated. Follow-up labs at one month showed Cr 1.50 mg/dL and the patient was restarted on levatinib and everolimus with continued durable response.

Discussion

While TKIs may induce TMA and mTOR inhibitors have been associated with proteinuria and ATN, our patient revealed a unique presentation of secondary MN that was likely induced by his relatively recent ICI therapy. MN can also present as a paraneoplastic lesion, but it is rarely associated with RCC and the presentation did not correlate with his improved CT scan. Given his deteriorating kidney function, treatment with rituximab was fortunately successful and allowed for continued treatment with durable cancer response.