Abstract: PUB196
Rapidly Progressive AKI After Alpelisib Therapy: Suspected Acute Interstitial Nephritis
Session Information
Category: Onconephrology
- 1600 Onconephrology
Authors
- Alsharif, Mhd Nezar, South Texas Health System, Edinburg, Texas, United States
- Patel, Lalitkumar, South Texas Health System, Edinburg, Texas, United States
- Savage-Lobeck, David, South Texas Health System, Edinburg, Texas, United States
- Garza, Joel F., South Texas Health System, Edinburg, Texas, United States
- Alsabbagh, Mourad, South Texas Health System, Edinburg, Texas, United States
Introduction
Acute interstitial nephritis (AIN) is a common cause of intrinsic acute kidney injury (AKI), most frequently triggered by medications. As targeted oncologic therapies become increasingly utilized, recognition of immune-mediated renal toxicities is essential. Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor used in metastatic breast cancer, has been associated with renal dysfunction; however, hypersensitivity-mediated AIN remains underrecognized.
Case Description
A 70-year-old woman with metastatic breast cancer developed rapidly progressive severe AKI shortly after initiation of alpelisib 300 mg daily. Her baseline estimated glomerular filtration rate was approximately 50 mL/min/1.73 m2. On presentation, serum creatinine was 10.22 mg/dL with blood urea nitrogen 62 mg/dL and estimated GFR 6 mL/min/1.73 m2. The patient reported a mild generalized rash shortly after starting therapy. Laboratory evaluation demonstrated leukocytosis (WBC 15 K/µL) with eosinophilia (17%; absolute eosinophil count 2.63 K/µL) and bicarbonate 18.7 mmol/L. Urinalysis showed leukocyte esterase 2+, protein 2+, blood 3+, and 15–19 white blood cells per high-power field. Urine microscopy demonstrated granular casts and moderate eosinophiluria. Urine sodium was 57 mmol/L with urine osmolality 279 mOsm/kg, consistent with intrinsic renal injury.
The combination of severe AKI, rash, eosinophilia, eosinophiluria, sterile pyuria, and temporal association with alpelisib initiation raised strong suspicion for drug-induced AIN. Alpelisib was discontinued, and prednisone 60 mg daily was initiated. Serum creatinine improved from 10.22 mg/dL to 7.85 mg/dL within 24 hours and further decreased to 4.0 mg/dL within 48 hours, with stabilization thereafter. Renal biopsy was deferred given the characteristic clinical features and rapid response to therapy.
Discussion
The temporal relationship between alpelisib exposure and severe AKI, combined with rash, eosinophilia, eosinophiluria, and sterile pyuria, strongly supports suspected drug-induced AIN. Rapid improvement following drug discontinuation and corticosteroid therapy favored a reversible immune-mediated process rather than acute tubular injury. The absence of severe hemodynamic instability or alternative nephrotoxic exposures further supported a medication-associated etiology.