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However, incidental renal radiation exposure presents a significant risk of radiation nephropathy, and this risk varies based on the unique characteristics of the radionuclide and its decay phenomenon as well as the peptide being utilized. This review explores the historical development of PRRT, the physics of radionuclide therapy as necessary for a practicing nephrologist, and key mechanisms of radiation-related kidney injury. We detail renal handling of radionuclides, dose thresholds and pathological features of PRRT-induced nephropathy. Furthermore, we discuss both current and prospective strategies to reduce renal toxicity\u2014such as amino acid infusions, receptor saturation, cleavable linkers and emerging protective agents. Special considerations for PRRT in patients with chronic kidney disease and those on dialysis are highlighted. As PRRT applications expand, multidisciplinary collaboration is essential to optimize renal safety.<\/jats:p>","DOI":"10.1093\/ndt\/gfaf121","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:36:11Z","timestamp":1751960171000},"page":"220-232","source":"Crossref","is-referenced-by-count":5,"title":["Peptide receptor radionuclide therapy: a new era of radiation nephropathy"],"prefix":"10.1093","volume":"41","author":[{"given":"Abhirami","family":"Das","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic Department of Medicine, , Jacksonville, FL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Tuba","family":"Kendi","sequence":"additional","affiliation":[{"name":"Mayo Clinic Department of Radiology, , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-7862","authenticated-orcid":false,"given":"Sandhya","family":"Manohar","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic Department of Medicine, , Jacksonville, FL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"2026013001365947400_bib1","doi-asserted-by":"publisher","first-page":"3S","DOI":"10.2967\/jnumed.116.186502","article-title":"Clinical history of the theranostic radionuclide approach to neuroendocrine tumors and other types of cancer: historical review based on an interview of Eric P. 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