Table 3.
Clinical manifestations of VEGF inhibition
| Druga | Class | Renal Manifestations (Level of Evidence) | References |
|---|---|---|---|
| Bevacizumab | mAb against VEGFA | Proteinuria 21%–62% (level 1), all-gradeb hypertension 23.6% and high-gradec hypertension 7.9% (level 1), renal TMA (levels 6 and 7), MCD/cFSGS-like glomerulopathy (level 6), ABMR-intraocular (level 7) | 8,9,34,37,38 |
| Ranibizumab (intraocular) | mAb against VEGFA | Systemic and renal TMA (level 7), proteinuria (level 7), ABMR-intraocular (level 7) | 46,47 |
| Aflibercept | Recombinant fusion protein | All-gradeb hypertension 42.4% and high-gradec hypertension 17.4% (level 1), proteinuria, TMA (level 6), ABMR-intraocular (level 7) | 9,40 |
| Ramucirumab | mAb against VEGFR2 | All-gradeb hypertension 21% (level 1), proteinuria 9% (level 1) | 39 |
| Sunitinib | Multitargeted TKI | All-gradeb hypertension 14.9% (level 1), MCD/cFSGS-like glomerulopathy (level 6), nephrotic syndrome (level 7) | 9,53,56 |
| Pazopanib | Multitargeted TKI | All-gradeb hypertension 47% (level 1), all-graded proteinuria 13.5% and high-grade proteinuria 2.2% (level 1) | 53,55 |
| Sorafenib | Multitargeted TKI | All-gradeb hypertension 18.1% (level 1), MCD/cFSGS-like glomerulopathy (level 6), TMA (level 6), all-graded proteinuria 11.6% and high-gradee proteinuria 0.9% (level 1) | 9,53,55 |
| Cabozantinib | Multitargeted TKI | All-gradeb hypertension 32.7% (level 1) | 53 |
| Vandetanib | Multitargeted TKI | All-gradeb hypertension 17.3% (level 1), all-graded proteinuria 10.0% and high-gradee proteinuria 0% (level 2) | 53,55 |
| Motesanib | Multitargeted TKI | All-gradeb hypertension 26.1% (level 1) | 53 |
| Cediranib | Multitargeted TKI | All-gradeb hypertension 42.5% (level 1), all-graded proteinuria 37.8% and high-gradee proteinuria 3.9% (level 1) | 53,55 |
| Axitinib | Multitargeted TKI | All-gradeb hypertension 27.1% (level 1), all-graded proteinuria 20.2% and high-gradee proteinuria 4.6% (level 1) | 53,55 |
| Regorafenib | Multitargeted TKI | All-gradeb hypertension 32.4% (level 1), all-graded proteinuria 7.0% and high-gradee proteinuria 1.4% (level 2) | 53,55 |
| Tivozanib | Multitargeted TKI | All-graded proteinuria 9.6% and high-gradee proteinuria 1.5% (level 1) | 55 |
| Linifanib | Multitargeted TKI | All-graded proteinuria 27.3% and high-gradee proteinuria 6.8% (level 1) | 55 |
| Dasatinib | Multitargeted TKI | Nephrotic syndrome (level 7) | 56 |
| Imatinib | Multitargeted TKI | Nephrotic syndrome (level 7) | 56 |
| Quizartinib | Multitargeted TKI | Nephrotic syndrome (level 7) | 56 |
| Vemurafenib | BRAF inhibitor | AKI, acute tubular necrosis (level 7) | 73 |
| Dabrafenib | BRAF inhibitor | Nephrotic syndrome with severe podocyte and endothelial cell injury when used in combination with trametinib (level 7) | 26 |
| Trametinib | MEK inhibitor | Nephrotic syndrome with severe podocyte and endothelial cell injury when used in combination with dabrafenib (level 7) | 26 |
Levels of evidence: level 1: systematic review or meta-analysis of RCTs; level 2: one well designed RCT; level 3: one controlled trial without randomization; level 4: case–control or cohort studies; level 5: systematic review of descriptive and qualitative studies; level 6: one descriptive or qualitative study; level 7: case series or case report. MCD/cFSGS-like, minimal change disease and/or collapsing FSGS; ABMR, Antibody Medicated Rejection.
All drug delivery routes are systemic unless otherwise specified.
All-grade hypertension: grades 1–4. Grade 1: asymptomatic transient increase in systolic BP/diastolic BP >20 mm Hg or <150/100 not requiring therapy; grade 2: recurrent or persistent or symptomatic increase in systolic BP/diastolic BP >20 mm Hg or >150/100, not requiring therapy; grade 3: 4equires therapy or more intensive therapy than previous; grade 4: hypertensive crisis.
High-grade hypertension: combined grades 3 and 4.
All-grade proteinuria: grades 1–5 (National Cancer Institute toxicity grading criteria version 2 and 3 for proteinuria). Grade 1: dipstick 1+ or 0.15–1.0 g/24 h; grade 2: dipstick 2+ to 3+ or 1.0–3.5 g/24 h; grade 3: dipstick 4+ or >3.5 g/24 h; grade 4: nephrotic syndrome; grade 5: death.
High-grade proteinuria: grades 3–5.