Abstract: FR-PO969
Glomerular Intracytoplasmic Vacuolization in a Patient Receiving Polyethylene Glycol Biopharmaceutical
Session Information
- Pathology and Lab Medicine - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Mauiyyedi, Shamila, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
- Lahoti, Amit, The University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, United States
- Tchakarov, Amanda, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
Introduction
Conjugation of biologics to HMW polyethylene glycol (PEG) enhances drug delivery/efficacy by extending half-life. Clearance of PEG causes cellular vacuolization by light microscopy in liver, spleen, brain and kidney in animal models. No human study, electron microscopy, or impact on cell function are reported. We report the first case of marked glomerular cytoplasmic vacuolization in a patient who received PEGylated nucleoside analog.
Case Description
A 67 year old male received PEGylated nucleoside analog for metastatic gastric carcinoma. Within 4 weeks of the drug being stopped due to disease progression, the patient developed 7 g/day proteinuria, cough, dyspnea, and edema. Studies showed a normal C3, C4 and negative ANCAs. Renal biopsy revealed focal segmental glomerulosclerosis with enlarged, reactive, vacuolated podocytes along with acute tubular epithelial injury with areas of tubular epithelial vacuolization. Immunofluorescence was negative. Electron microscopy (Fig. 1) revealed extensive intracytoplasmic vacuolization in glomerular podocytes (P), endothelium (gE), mesangial cells (M), tubular epithelial cells (T) and peritubular capillary endothelium (ptcE). Vacuoles were membrane bound, colorless and variably sized 0.3-6.5 μm. Some vacuoles contained granular material but majority were empty. No zebra bodies were seen. Podocytes had the most prominent vacuoles plus extensive foot process effacement.
Discussion
We report the first case of marked intracytoplasmic vacuolization related to PEG in renal glomerular, endothelial and tubular cells. Animal studies suggest vacuolization may be an adaptive response to clear PEG rather than a toxic effect. However, we hypothesize that PEG vacuoles can alter cell function with pathological changes and adverse clinical outcome, such as the podocytopathy seen in this case. Further clinical studies are needed to understand the safety of PEGylated therapies.