A CASE OF FIBRILLARY GLOMERULONEPHRITIS ASSOCIATED WITH PEMBROLIZUMAB USE DURING BREAST CANCER TREATMENT

Document Type

Conference Proceeding

Publication Date

4-1-2025

Publication Title

Am J Kidney Dis

Abstract

Prior studies have enumerated various immune-mediated effects of which 1-2% involve the kidneys, starting from 10 days of initiation up to 3 months after discontinuation. AIN is the most common picture, although other pathologies like ATN, MCD, IgA nephropathy, FSGS, crescenteric GN, anti-GBM GN, C3 GN and ANCA-associated vasculitis have also been demonstrated. 4 cases of fibrillary glomerulonephritis (FGN) were ascribed to nivolumab, ipilimumab and atezolizumab, however, this report possibly describes the first occurrence related to pembrolizumab. A 73-year-old Caucasian female, with no history of CKD or proteinuria, was treated for invasive ductal carcinoma with pembrolizumab, doxorubicin and cyclophosphamide. Within 3-4 days of completing the 3rd cycle, she developed new-onset hypertension, with a corresponding creatinine rise from 0.94 to 2.05 mg/dL in 1 month and urine Alb/Cr ratio of 8253.8 mg/g. Renal biopsy revealed fibrillary glomerulopathy with moderate interstitial fibrosis and tubular atrophy. The only remarkable immunologic workup was a positive ANA. Creatinine appeared to improve initially with a prednisone taper over 5 months but eventually progressed to 2 mg/dL in 2 years. At 1 year, empagliflozin was added to stabilize proteinuria successfully. FGN is an infrequent renal disease with characteristic disorderly fibrils on microscopy. Although the exact mechanism remains unascertained, it has been linked to multiple malignancies including 5 cases of breast cancer. Higher age, creatinine and proteinuria worsen the prognosis with nearly 50% progressing to ESRD within 4 years, despite steroids and cytotoxic agents. In this case, FGN could reasonably correlate with both breast cancer and pembrolizumab use. However, the timing of disease onset in the setting of cancer remission favors the latter. In summary, considering the novelty of immune checkpoint inhibitors, an AKI attributable to their use demands early recognition to avoid potentially inappropriate treatment and grave consequences. Multicenter controlled trials can further uncover therapeutic options to prevent FGN progression.

Volume

85

Issue

4 Suppl 1

First Page

S83

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