Prevention and treatment
To minimise the risk of cisplatin-induced kidney adverse events, adequate preventative and supportive care measures (as per local institutional policies) are advised for all patients receiving cisplatin. This includes appropriate antiemetics, maintaining adequate euvolemia, monitoring urine output throughout hydration pre- and post-infusion and preventing salt wasting with magnesium and potassium supplementation.r rr
However, given the differences in cancer types, cisplatin doses, study types, hydration regimens, and definitions of nephrotoxicity across studies, no definitive conclusions can be made regarding optimal hydration regimens.r
Diuresis induction with intravenous sodium chloride 0.9%
The administration of intravenous isotonic sodium chloride 0.9% to induce diuresis continues to be the primary approach for preventing CIN and is recommended for all patients receiving cisplatin containing regimens. However, the optimal hydration solution and regimen to prevent nephrotoxicity associated with cisplatin administration remain unclear.
The use of hypertonic sodium chloride or dextrose/sodium chloride is not recommended.
Volume and duration of hydration
Systematic review of 24 studies supports the effectiveness and safety of short-duration (2 to 6 hours), lower-volume (2 to 4 L) hydration with magnesium supplementation in preventing CIN, even at intermediate- to high-dose levels.r eviQ default hydration regimens align with this recommendation.
Supplementation in hydration regimens
The main objective of hydration during cisplatin therapy is to maintain sufficient urine flow, thereby facilitating the drug's elimination from the kidneys and minimising the risk of kidney damage.
The rationale for adding potassium and magnesium to sodium chloride 0.9% is to avoid the development of hypokalaemia and hypomagnesaemia that may occur with forced diuresis; in addition, magnesium supplementation may help to limit CIN.r
Magnesium: Cisplatin and magnesium affect the same sodium and water channels in the outer medulla, leading to magnesium depletion induced by cisplatin. This depletion can enhance cisplatin nephrotoxicity.
To minimize the risk of CIN, it is important to manage hypomagnesaemia in accordance with local policy before and during cisplatin treatment. There is robust evidence supporting the effectiveness of this approach.
In alignment with these considerations, the default prehydration regimen includes magnesium sulfate supplementation. This regimen incorporates 10 mmol of magnesium sulfate (MgSO4) in 1000 mL of sodium chloride 0.9%, regardless of the administered cisplatin dose.
Potassium: Cisplatin does not result in significant potassium loss, and the administration of intravenous sodium chloride 0.9% helps maintain fluid balance, promoting urine production, without requiring additional potassium supplementation.
It has been shown that cisplatin (at doses 60 to 80 mg/m2) can be safely administered to patients with nephrotoxicity or low potassium levels using a short hydration method, even in the absence of potassium chloride (KCL) supplementation.r
The eviQ default prehydration regimen does not include potassium supplementation for this reason.
Unclear role of mannitol
Although many hydration regimens include the use of either mannitol or furosemide, there is no good evidence that diuretics provide any added benefit.
Routine use of mannitol to prevent nephrotoxicity during cisplatin therapy lacks clear evidence. However, in specific situations like high-dose cisplatin (≥100 mg/m2) or pre-existing hypertension, it may be considered appropriate, although the supporting evidence is not compelling.r
On balance, and given the practical challenges of its use, mannitol is not included in the eviQ recommended hydration schedules below with a footnote added to suggest considering its use in cases of high-dose cisplatin (≥100 mg/m2) or pre-existing hypertension.
Cisplatin dose modifications
There are a lack of pharmacokinetic studies evaluating cisplatin dose reductions in kidney dysfunction in the non-kidney replacement therapy (KRT) setting. Several observational studies suggest that cisplatin dose reduction in kidney dysfunction (with the aim to reduce cumulative cisplatin exposure) may decrease the risk of adverse events.rr r
The impact of cisplatin dose reduction on therapeutic efficacy is largely unknown due to the exclusion of patients with kidney dysfunction in many clinical trials.
For eGFR < 60 mL/min/1.73 m2, to ensure therapeutic dosing and reduce the risk of a further decline in kidney function from cisplatin-induced renal adverse events, directly mGFR is preferred for initial dosing, especially where either:
- cisplatin dose > 50 mg/m2
- eGFR is unreliable (e.g., extremes of body composition, amputees, paraplegia, conditions of skeletal muscle).
Refer to the cisplatin monograph in the International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) for dosing recommendations according to kidney function.
High peak plasma concentration of cisplatin has been shown to increase the risk of cisplatin nephrotoxicity. Case reports have documented instances where a single standard dose of cisplatin resulted in an increase in serum creatinine levels. However, after the recovery of kidney function, subsequent administration of split doses of cisplatin was carried out without any harmful impact on measured kidney function. This suggests that dividing the cisplatin dose into multiple administrations may help reduce the risk of nephrotoxicity compared to a single high-dose infusion.r
However, in kidney dysfunction, fractionating cisplatin doses over several consecutive days does not appear to significantly reduce the incidence of cisplatin-related adverse events (e.g., renal adverse events, haematological toxicities) in kidney dysfunction. r r
Substitution with carboplatin
Carboplatin is a less nephrotoxic analogue of cisplatin and has been substituted in many chemotherapy regimens. This substitution should be implemented solely with substantial supporting evidence. Before using carboplatin, it is essential to evaluate the comparative efficacy of cisplatin and carboplatin across different diseases.