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Kidney Week

Abstract: PO2194

Crescentic Glomerulonephritis and Phospholipase A2 Receptor-Positive Membranous Nephropathy in a Lung Cancer Patient on an Immune Checkpoint Inhibitor

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Abramson, Matthew, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
  • Jaffer Sathick, Insara, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction

Acute kidney injury (AKI) occurs in 3% of patients on immune checkpoint inhibitors (ICPI), usually due to interstitial nephritis, yet the array of ICPI-mediated AKI is not fully understood, with rare reports due to Crescentic Glomerulonephritis (cGN). To date there is no known case of PLA2R-positive Membranous Nephropathy (MN) associated with ICPI. Here we report the first case of ANCA-negative cGN with PLA2R MN, which developed after initiation of ICPI, with response to rituximab (RTX).

Case Description

Nephrology was consulted for AKI and hematuria in a 67-year-old male smoker with lung adenocarcinoma. He started on pembrolizumab and pemetrexed 8 months ago, last doses 3 weeks prior to consult. He developed throat irritation from local irradiation, and pantoprazole was initiated. No NSAIDs, herbal medications or iodinated contrast exposure. Prior to treatment, baseline Creatinine (Cr) was 0.8mg/dL and urinalysis (UA) was negative for albuminuria.
Blood pressure was 112/66, and no edema was present. Cr was elevated at 3.7 mg/dL. UA showed 3+ protein, >50 RBC, 10-25 WBC, and no pathologic casts. Renal sonogram was normal. Urine protein:creatinine ratio (UPC) was 1.52g/g. Complements were normal. Serology workup (pANCA/cANCA/MPO/PR3, ANA, anti-PLA2R) was negative.
Kidney biopsy showed diffuse cGN [Glomeruli: necrosis (2/38), cellular crescents (10/38), and fibrocellular crescents (6/38)], diffuse PLA2R-positive glomerular deposits, focal tubular atrophy, and minimal interstitial fibrosis/inflammation. EM showed thickened basement membranes, focal subepithelial granular deposits and early spike formation, and 30% foot-process effacement. ICPI was discontinued and prednisone 60mg daily was started. Cr nadir’ed at 2.3mg/dL, but uptrended to 3.1mg/dL over 4 weeks; UPC increased to 2.59. He then received 4 doses of RTX over 8 weeks and was started on vinorelbine. UPC and Cr improved to 2.18 and 2.5mg/dL, respectively, and NSCLC disease stabilized.

Discussion

Interstitial nephritis is often implicated in AKI related to ICPIs, but rarely other pathologies are reported. Renal biopsy should be considered in patients with atypical features suggestive of GN. Given that our patient’s biopsy showed cGN and PLA2R MN, we opted to treat with RTX, which has resulted in improvement in renal function and proteinuria.