Kidney Week

Abstract: FR-PO1270

Anti-LRP2 Nephropathy in a Patient on PD-L1 Inhibitor Therapy

Session Information

• Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Alahmadi, Ziad, Johns Hopkins University, Baltimore, Maryland, United States

Ziad Alahmadi, MBBS

• Lopez Madrid, Rosario Michelle, Johns Hopkins University, Baltimore, Maryland, United States

Rosario Michelle Lopez Madrid, MD

• Wilkins, Reid C., Johns Hopkins University, Baltimore, Maryland, United States

Reid C. Wilkins, MD

• Monroy-Trujillo, Jose Manuel, Johns Hopkins University, Baltimore, Maryland, United States

Jose Manuel Monroy-Trujillo, MD

• Cervantes, C. Elena, Johns Hopkins University, Baltimore, Maryland, United States

C. Elena Cervantes, MD

Introduction

Anti-LRP2 positive tubulointerstitial nephritis is identified as autoantibodies targeting proximal tubular epithelial receptors, causing immune complex deposition in tubular basement membranes (TBMs). Immune checkpoint inhibitor therapy can trigger diverse autoimmune processes including acute interstitial nephritis but rarely manifesting with distinct concurrent pathologies. We present a case of anti-LRP2 tubulointerstitial nephritis in a patient receiving durvalumab (PD-L1 inhibitor)

Case Description

A 74-year-old man with invasive urothelial carcinoma status post radical cystectomy with ileal conduit and neoadjuvant cisplatin/gemcitabine/durvalumab was admitted with Klebsiella bacteremia from urinary source. He was found with acute kidney injury (AKI) with creatinine (Cr) of 6 mg/dL (baseline 1.2 mg/dL). CT abdomen showed stable mild bilateral hydronephrosis attributed to ileal conduit. Urinalysis was consistent with UTI and urine protein to creatinine ratio was 1.56 g/g. Kidney biopsy was done and showed acute tubulointerstitial nephritis, neutrophilic predominant, suggestive of pyelonephritis, and focal membranous nephropathy with TBM deposits. Immunohistochemistry was positive for NELL-1 and LRP2, suggesting NELL-1 membranous nephropathy and LRP2 anti brush border disease (ABBA). Creatinine improved with antibiotics and supportive care. Durvalumab was restarted and subsequently the patient had recurrent AKI. Repeat biopsy showed acute on chronic tubulointerstitial inflammation and TBM immune complex deposition consistent with ABBA (Figure 1). Durvalumab was discontinued and the patient was initiated on oral prednisone 60 mg with a 10-week taper and Cr stabilized at 2.6 mg/dL

Discussion

ABBA is a rare disease caused by circulating IgG autoantibodies against LRP2 (megalin). PD-L1 is expressed on proximal tubular epithelial cells and by blocking it with durvalumab, loss of immune tolerance against tubular antigens as LRP2 can develop. Anti-LRP2 positivity on initial biopsy was an early finding and likely progressed upon continuation of durvalumab. ABBA secondary to immune checkpoint inhibitors has not been reported