From the Guidelines
Oxaliplatin and cisplatin cause distinct renal tubular damage, with oxaliplatin being less nephrotoxic and causing less severe damage compared to cisplatin. The mechanisms of nephrotoxicity for both platinum-based chemotherapeutic agents involve proximal tubular injury, oxidative stress, and inflammation, but the severity and frequency of damage differ significantly 1. Key differences in their molecular structure and biotransformation pathways contribute to the reduced nephrotoxicity of oxaliplatin, with its diaminocyclohexane ligand reducing reactivity with kidney tissues and resulting in less toxic metabolites. Some notable points about the nephrotoxic effects of these drugs include:
- Cisplatin commonly causes acute kidney injury in 20-30% of patients, characterized by severe tubular necrosis, decreased glomerular filtration rate, and electrolyte disturbances.
- Oxaliplatin rarely causes clinically significant nephrotoxicity, with renal dysfunction occurring in less than 5% of patients.
- Patients receiving oxaliplatin should still have renal function monitored, particularly those with pre-existing kidney disease or risk factors for nephrotoxicity.
- Aggressive hydration protocols typically used with cisplatin are not routinely required for oxaliplatin administration, highlighting the difference in nephrotoxic potential between the two drugs 1. Overall, while both drugs can cause renal tubular damage, the severity and frequency of this damage are significantly lower with oxaliplatin compared to cisplatin, making oxaliplatin a preferable option when considering the risk of nephrotoxicity 1.
From the Research
Renal Tubular Damage Comparison
- The renal tubular damage associated with oxyplatin and cisplatinum is not identical, but both can cause nephrotoxicity [ 2, 3 ].
- Cisplatin has been shown to cause dose-dependent renal toxicity, with unbound cisplatin being freely filtered at the glomerulus and taken up into renal tubular cells, leading to tubular damage and dysfunction [ 2 ].
- Oxaliplatin, on the other hand, has been reported to cause various forms of nephrotoxicity, including renal tubular vacuolization, acute tubular necrosis, renal tubular acidosis, and acute kidney injury secondary to hematological toxicity [ 3 ].
Mechanisms of Injury
- The mechanisms of injury for cisplatin and oxaliplatin are not fully understood, but it is believed that both drugs can cause direct cytotoxicity, oxidative stress, and apoptosis in renal tubular cells [ 2, 4 ].
- Cisplatin has been shown to accumulate in the kidney tubules and cause acute kidney injury through various mechanisms, including DNA damage and oxidative stress [ 4 ].
Prevention and Management
- Hydration and diuresis have been shown to decrease the incidence of nephrotoxicity in patients receiving cisplatin therapy [ 5 ].
- The administration of magnesium and mannitol may also assist in maintaining renal function and reducing nephrotoxicity in adults receiving cisplatin [ 5 ].
- Monitoring for renal function abnormalities and hemolysis should be considered during oxaliplatin-based chemotherapy [ 3 ].