{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:18:07Z","timestamp":1792124287947,"version":"4.4.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antibody\u2013drug conjugates (ADCs) have transformed solid-tumor therapy and are increasingly benchmarked directly against physician\u2019s-choice chemotherapy. However, kidney adverse events and electrolyte disturbances remain inconsistently captured across trials and are often interpreted without a unified pharmacological framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review proposes a mechanism-informed narrative framework linking ADC architecture, intracellular processing, and payload exposure pathways to renal injury and electrolyte phenotype hypotheses while contextualizing these patterns against canonical renal-electrolyte programs of conventional cytotoxic chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach<\/jats:title>\n                    <jats:p>We conducted a targeted literature review prioritizing randomized or registrational trials, regulatory labels, real-world or pharmacovigilance data when informative, and phenotype-defining case reports supported by urinary indices, biopsy, or both when available. Evidence is presented using explicit source-level stratification rather than quantitative pooling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Messages<\/jats:title>\n                    <jats:p>Intact ADCs are IgG-based macromolecules with limited glomerular filtration under an intact filtration barrier, whereas released small-molecule payloads or payload-containing catabolites may gain a filtration advantage and create proximal tubular exposure. Comparative studies support toxicity redistribution rather than uniform toxicity reduction. Enfortumab vedotin most often illustrates a systemic\/prerenal acute kidney injury (AKI) axis driven by hyperglycemia, diabetic ketoacidosis, infection, and dehydration; sacituzumab govitecan combines gastrointestinal volume depletion with rare biopsy-proven acute tubulointerstitial nephritis; and trastuzumab deruxtecan has generated a hypothesis-defining Fanconi-like proximal tubule signal. Kidney tissue, especially the proximal tubule, contains protease-rich endolysosomal and apical brush-border systems that make renal processing of ADC-derived material biologically plausible, but kidney-specific proof remains limited. Because creatinine-based endpoints may miss mild tubular injury, future ADC programs should consider electrolyte-focused monitoring and the exploration of tubular injury biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A trafficking-aligned taxonomy may improve the interpretation of ADC-associated renal and electrolyte events. Kidney Disease: Improving Global Outcomes (KDIGO)-aligned kidney endpoints, standardized electrolyte reporting, and prospective validation of tubular injury biomarkers should be priorities for future ADC trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1824554","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T08:30:07Z","timestamp":1782462607000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From intracellular processing to renal phenotypes: a mechanism-informed framework for interpreting kidney injury and electrolyte patterns with antibody\u2013drug conjugates in solid tumors"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuxin","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikun","family":"Wang","sequence":"additional","affiliation":[{"name":"Nephropathy Department, The Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nephropathy Department, The Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1203073","DOI":"10.3389\/fimmu.2023.1203073","article-title":"Antibody-drug conjugates: the paradigm shifts in targeted cancer therapy","volume":"14","author":"Aggarwal","year":"2023","journal-title":"Front. 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