Table 1.
Incidence of renal manifestations and electrolytic disorders under anti-angiogenic targeted therapies.
| Drugs | Molecular Targets | Tumor Targets | Adverse Events (Incidence) | Electrolytic Disorders | References |
|---|---|---|---|---|---|
| Monoclonal antibodies | |||||
| Bevacizumab | VEGF | CRC, NSCLC, RCC, GBM, epithelial ovarian cancer, primary peritoneal cancer, cervical cancer, fallopian cancer, glioblastoma, ocular diseases | HTN (23–41%), Proteinuria (2–32%) | Hypophosphatemia, Hyponatremia | [38,39,40,41,42,43,44,45,46,47,48] |
| Ranibizumab | VEGF | Ocular diseases | HTN, Proteinuria | - | [38,39] |
| Ramucirumab | VEGFR2 | CRC, NSCLC, GC | HTN, Proteinuria | - | [38,39] |
| Recombinant fusion protein | |||||
| Aflibercept | VEGF | CRC, ocular diseases | HTN, Proteinuria | - | [38,39] |
| Multitargeted TKI | |||||
| Sorafenib | VEGFRs, PDGFRs, RAF, c-Kit, FLT3, Ret | RCC, HCC, DTC | HTN (17–55%), Proteinuria (10%) | Hypophosphataemia (16–85%), Hyponatremia (39%) | [49,50,51,52,53,54,55,56,57,58] |
| Sunitinib | VEGFRs, PDGFRs, FLT3, CSF1R, Ret | RCC, GIST, pNETs | HTN (22–60%), Proteinuria (10–65%) | Hypophosphatemia, Hyponatremia | [59,60,61,62,63,64,65,66] |
| Pazopanib | VEGFRs, PDGFRs, FGFR1, c-Kit | RCC, STS | HTN (40–52%), Proteinuria (13.5–18%) | Hypophosphatemia (34%), Hypocalcemia (33%), Hyponatremia (31%), Hypomagnesemia (11%) | [49,50,67,68,69,70,71,72,73] |
| Vandetanib | VEGFRs, EGFR, Ret | MTC | HTN (23.5–84%), Proteinuria (5.6–26%) | Hypomagnesemia (10–40%)Hypocalcemia (4–29%)Hypokaliemia (4–17%) | [5,50,74,75,76,77,78,79] |
| Axitinib | VEGFRs, PDGFRs, c-Kit | RCC | HTN (40–64%), Proteinuria (4.6–23%) | Hyponatremia, Hypophosphatemia (13%), Hypocalcemia (39%) | [5,49,50,80,81,82,83] |
| Regorafenib | VEGFRs, PDGFRs, FGFRs, Tie2, c-Kit, Ret, RAF | GIST, CRC, HCC | HTN (13–59%), Proteinuria (7–9.4%) | Hypophosphataemia (5–18%) | [5,49,50,55,84,85,86] |
| Cabozantib | VEGFRs, c-Met, AXL, c-Kit, FLT3, Ret | MTC, RCC | HTN (7–16), Proteinuria (6%) | Hypophosphatemia (4–8%) | [5,87,88,89,90,91] |
| Nintedanib | VEGFRs, PDGFRs, FGFRs, SRC | IPF, NSCLC | HTN, Proteinuria | - | [92] |
| Lenvatinib | VEGFRs, FGFRs, PDGFRa, Ret, c-Kit | DTC, RCC, HCC | HTN (45–100%), Proteinuria (26.9–100%) | Hypophosphatemia (45%) | [5,55,93] |
| Dasatinib | BCR-ABL, SRC, LCK, YES, FYN, c-Kit, VEGFR, PDGFR | CML, Ph+ ALL | Proteinuria | Hyponatremia | [94,95] |
| Ponatinib | VEGFRs, BCR-ABL, FLT3, Ret, c-Kit, FGFRs, PDGFR | CML, Ph+ ALL | HTN (9–32%) | - | [96,97,98] |
CML: chronic myeloid leukemia; CRC: colorectal cancer; CSF1R: colony stimulating factor 1 receptor; DTC: differentiated thyroid cancer; FGFR: fibroblast growth factor receptor; FLT3: fms like tyrosine kinase 3; GBM: glioblastoma multiforme; GC: gastric cancer (or gastroesophageal junction adenocarcinoma); GIST: gastrointestinal stromal tumor; HCC: hepatocellular carcinoma; HTN: hypertension; IPF: idiopathic pulmonary fibrosis; LCK: lymphocyte-specific protein tyrosine kinase; MTC: medullary thyroid cancer; NSCLC: non-small cell lung cancer; PDGFR: platelet-derived growth factor; Ph+ ALL: Philadelphia-chromosome-positive acute lymphoblastic leukemia; pNETs: progressive pancreatic neuroendocrine tumors; RAF: rapidly accelerated fibrosarcoma; RCC: renal cell carcinoma; STS: soft tissue sarcoma; VEGF: vascular endothelial growth factor; VEGFR: vascular endothelial growth factor receptor.