Table 1.
Summarized kidney adverse effects from anticancer therapies
| Drug Class | Drug Name | Mechanism of Injury | Kidney Effect |
|---|---|---|---|
| Conventional chemotherapy | |||
| Platinum-based | Cisplatin, carboplatin, oxaliplatin. | Platinum-DNA adducts mediate arrest of cell cycle, initiate apoptosis. ATP depletion. | ATI, renal magnesium wasting, proximal tubulopathy, NDI |
| Antimetabolite | Methotrexate | Intratubular crystal formation. Afferent arteriolar constriction | Crystal nephropathy, ATI |
| Gemcitabine | Endothelial injury | TMA, HTN | |
| Pemetrexed | Unknown | ATI, chronic interstitial fibrosis, proximal tubulopathy, NDI | |
| Alkylating agent | Cyclophosphamide | Toxic metabolite, acrolein | Hemorrhagic cystitis |
| Ifosfamide | Toxic metabolite, chloroacetaldehyde | ATI, proximal tubulopathy, NDI | |
| Melphalan | Increase ADH release | SIADH | |
| Nitrosoureas | Alkylation of tubular cell proteins | Chronic interstitial nephritis | |
| Antitumor antibiotics | Mitomycin C | Endothelial injury | TMA, HTN |
| Targeted therapy | |||
| VEGF inhibitors | Bevacizumab | Endothelial injury | TMA, HTN, ATI |
| Tyrosine kinase inhibitors | Sorafenib, sunitinib, axitinib, pazopanib, lenvatinib. | Endothelial injury, podocyte injury. | ATIN, ATI, TMA, FSGS |
| BCR-ABL tyrosine kinase inhibitor | Imatinib, dasatinib. | Tubular injury, endothelial injury | ATI, TMA |
| BRAF inhibitors | Vemurafenib, dabrafenib | Tubular injury, ERK activation | ATIN, ATI |
| BCL-2 inhibitors | Venetoclax | Tubular injury | AKI, TLS |
| ALK inhibitors | Crizotinib, lorlatinib, alectinib | Inhibition of creatinine secretion, renal arteriolar myocyte vacuolization | Pseudo-AKI, ATIN, ATI, kidney cyst, podocytopathies |
| CDK4/6 inhibitors | Palbociclib, ribociclib | Inhibit MATE1 and MATE2 transporters | Pseudo-AKI, ATI |
| PARP inhibitors | Olaparib, talazoparib | Inhibition of creatinine secretion | Pseudo-AKI |
| MET tyrosine kinase | Capmatinib, tepotinib | Inhibition of creatinine | Pseudo-AKI |
| EFGR monoclonal antibodies | Cetuximab, panitumumab | Inhibition of EGFR signaling at the DCT | Renal magnesium wasting |
| mTOR inhibitors | Everolimus | Decrease cubilin and megalin, VEGF inhibition | ATI, podocytopathies |
| Protease inhibitors | Bortezomib, carfilzomib | Endothelial injury, autoantibody formation | TMA, HTN |
| BTK inhibitors | Ibrutinib | Endothelial injury | ATI, HTN |
| XPO inhibitor | Selinexor | Volume depletion | Hemodynamic AKI, hyponatremia |
| Immunotherapies | |||
| CAR-T therapy | Axicabtagene ciloleucel, idecabtagene vicleucel, brexucabtagene autoleucel, tisagenlecleucel. | Systemic hyperinflammatory state. Ischemic injury | ATI, hemodynamic mediated AKI |
| CTLA-4 inhibitor | Ipilimumab, tremelimumab | Tubular injury, endothelial injury, podocyte injury | ATIN, ATI, MCD, lupus-like GN, necrotizing GN, TMA |
| PD-1 inhibitors | Pembrolizumab, cemiplimab, nivolumab | Tubular injury, endothelial injury, podocyte injury | ATIN, ATI, MCD, IgA nephropathy, FSGS, necrotizing GN, amyloidosis, immune complex–mediated GN |
| PDL-1 inhibitor | Atezolizumab, avelumab, durvalumab | Tubular injury | ATIN, ATI |
ATP, adenosine 5'-triphosphate; ATI, acute tubular injury; NDI, nephrogenic diabetes insipidus; TMA, thrombotic microangiopathy; HTN, hypertension; BTK, Bruton tyrosine kinase; SIADH, syndrome of inappropriate antidiuretic hormone secretion; VEGF, vascular endothelial growth factor; ATIN, acute tubulointerstitial nephritis; FSGS, focal segmental glomerulosclerosis; BCR-ABL, breakpoint cluster region-tyrosine protein kinase ABL-1 gene; BRAF, proto-oncogene B-Raf; BCL-2, B cell lymphoma 2 gene; TLS, tumor lysis syndrome; ALK, anaplastic lymphoma kinase; CDK4/6, cyclin-dependent kinase 4/6; MATE, multidrug and toxin extrusion; PARP, poly-ADP-ribose polymerase; MET, mesenchymal-epithelial transition; EFGR, epidermal growth factor receptor; DCT, distal convoluted tubule; mTOR, mammalian target of rapamycin; XPO, export protein exportin 1; CAR-T, chimeric antigen receptor T cells; CTLA-4, cytotoxic T-lymphocyte–associated protein 4; MCD, minimal change disease; PD-1, programmed cell death protein 1; FSGS, focal segmental glomerulosclerosis; PDL-1, programmed death-ligand 1 ERK, extracellular signal-regulated kinase.