Society of Diabetic Nephropathy Prevention Journal of Nephropharmacology 2345-4202 15 2 2026 07 01 Proximal tubular trap; radiation nephropathy risks from peptide reabsorption in peptide receptor radionuclide therapy for neuroendocrine tumors e12854 e12854 10.34172/npj.2026.12854 EN Naeem Nikpour https://orcid.org/0000-0002-4265-5430 Reza Farzaneh https://orcid.org/0009-0001-9074-2918 Mohammad Mehdi Darzi https://orcid.org/0009-0005-1352-0210 Simin Zeinadini https://orcid.org/0009-0002-9555-6759 Setare Sadeghi https://orcid.org/0009-0005-1026-344X Zahra Eydizadeh https://orcid.org/0009-0005-5411-6417 Zahed Karimi https://orcid.org/0000-0001-7455-5373 Elham Kebriyaei https://orcid.org/0009-0002-4557-7412 Rasoul Jafari Arismani https://orcid.org/0000-0001-7440-0507 Journal Article 10.34172/npj.2026.12854 2026 01 04 2026 03 16 Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs like 177Lu-DOTATATE) is highly effective for metastatic neuroendocrine tumors (NETs). However, a significant dose-limiting toxicity is radiation-induced nephropathy, primarily driven by a phenomenon termed the proximal tubular trap. Following glomerular filtration, radiolabeled peptides are avidly reabsorbed by proximal tubular epithelial cells (PTECs) via the megalin/cubilin receptor-mediated endocytosis pathway. This intracellular retention concentrates the radionuclide within the tubules, leading to prolonged, localized irradiation of renal tissue, particularly the radiosensitive proximal tubules and microvasculature. Cumulative radiation exposure causes DNA damage, oxidative stress, inflammation, and ultimately progressive tubular atrophy, interstitial fibrosis, and glomerulosclerosis, manifesting clinically as declining glomerular filtration rate (GFR), proteinuria, and potentially end-stage renal disease months to several years post-therapy.