Table 2.
List of targeted agents which cause nephrotoxicity
| Agent | Nephrotoxic effect | Associated conditions | Management | References |
|---|---|---|---|---|
| EGFR inhibitors | Inhibition of EGFR signaling at the distal convoluted tubule, which functions in transepithelial magnesium transport; failure to maintain tubular integrity through EGFR | Electrolyte disturbance (hypomagnesemia, hypophosphatemia, hypokalemia), diffuse proliferative glomerulonephritis, nephrotic syndrome, hypoalbuminemia | Nephrotic syndrome management through fluid and sodium restriction, oral or IV diuretics, and ACE inhibitors; magnesium wasting management by IV magnesium infusion and oral magnesium supplementation; discontinuation | [3,61,109,110] |
| Cetuximab | ||||
| Panitumumab | ||||
| mTOR inhibitors | Inconclusive and multifactorial mechanism with possible increased glomerular permeability and injury and suppression of tubular renal cell compensatory proliferation/survival/repair processes | Glomerulopathy, AKI, proteinuria | Close monitoring of proteinuria and renal damage; early use of ACE inhibitors and ARBs with sirolimus; discontinuation | [67-71] |
| Temsirolimus | ||||
| B-Raf inhibitors | Damage to proximal tubules, inhibiting tubular secretion; reduction in GFR and creatinine clearance | Acute interstitial nephritis, acute tubular necrosis, AKI, Fanconi’s syndrome, hypertension | Routine monitoring of serum creatinine and electrolytes; discontinuation | [3,75,76,111] |
| Vemurafenib | ||||
| Anti-angiogenesis (VEGF and VEGFR inhibitors) | Anti-VEGF antibodies inhibition of endothelial cell proliferation and blood vessel formation, resulting in loss of filtration barrier; nitric oxide pathway inhibition and oxidative stress inducing endothelial dysfunction and capillary rarefaction | Nephrotic syndrome with high-grade proteinuria, AKI, TMA, hypertension | Hypertension management through ACE inhibitor, ARBs; discontinuation | [3,57,112,113] |
| Bevacizumab | ||||
| Sorafenib | ||||
| Sunitinib | ||||
| Immune Checkpoint Inhibitors | Enhanced T cell response with migration of activated T cells into the kidney; immune responses leading to inflammatory cell infiltrates; podocyte effacement | Acute tubulointerstitial nephritis, immune complex glomerulonephritis, TMA, AKI with possible granulomas | Corticosteroids; discontinuation | [3,58,80] |
| Ipilimumab | ||||
| Pembrolizumab | ||||
| Nivolumab | ||||
| CAR-T therapy | CAR-T cell expansion and stimulation of immune cell-secreting cytokines; fever, hypotension, renal failure | CRS; AKI | Tocilizumab | [86,88,89,91,92] |
| Cytokine therapy | Activation of TNF-alpha and other cytokines to induce capillary leak syndrome and renal hypoperfusion | Pre-renal azotemia; AKI | Fluid bolus; intermediate-dose dopamine; discontinuation | [93-98] |
| IL-2 |