Why Hyperhydration is Given in Pediatric ALL
Hyperhydration is administered to children with acute lymphoblastic leukemia primarily to prevent methotrexate-induced nephrotoxicity by maintaining high urine output and alkalinization, which reduces methotrexate precipitation in renal tubules and accelerates drug elimination.
Primary Mechanism of Renal Protection
Aggressive intravenous hydration with alkaline solution prevents methotrexate crystal precipitation in the renal tubules, which is the main cause of acute kidney injury during high-dose methotrexate therapy 1.
The standard hydration rate is 125 mL/m²/hour administered before, during, and after methotrexate infusion to maintain brisk urine output and facilitate drug clearance 2, 3.
Urine alkalinization (maintaining pH >7.0) combined with hydration increases methotrexate solubility in the renal tubules, further reducing precipitation risk 1.
Impact on Drug Clearance and Toxicity
Greater hydration volumes significantly lower methotrexate plasma concentrations at critical time points (21-hour and 44-hour levels), directly reducing systemic drug exposure and toxicity risk 1.
A study comparing hydration regimens demonstrated that optimized hydration reduced severe toxicity from 16% to 6% in pediatric ALL patients receiving 2 g/m² methotrexate 1.
For patients with delayed methotrexate clearance, increasing hydration from 125 to 200 mL/m²/hour significantly decreases both methotrexate levels and serum creatinine at all measured time points 2.
Clinical Context in ALL Treatment Protocols
High-dose methotrexate (1-5 g/m² for low-risk, up to 5 g/m² for high-risk ALL) is a core component of consolidation therapy in enhanced-resource settings, making nephrotoxicity prevention essential 4.
Renal toxicity occurs in 18.5% of HDMTX 5 g/m² infusions and 40% of HDMTX 8 g/m² infusions even with standard supportive care, underscoring the importance of adequate hydration 5.
The Asian Oncology Summit guidelines specify that intermediate-dose methotrexate (1 g/m² over 24 hours) requires leucovorin rescue at 10 mg/m² starting at 42 hours, with increased rescue based on elevated creatinine, demonstrating the direct link between renal function and methotrexate toxicity management 4.
Important Caveats About Hydration Duration
Extending prehydration beyond 4 hours (to 12 hours) does NOT reduce renal toxicity or improve methotrexate clearance, so standard 4-hour prehydration is sufficient 5.
Recent evidence suggests that reduced post-hydration (62.5 mL/m²/hour) may be equally safe as standard rates while potentially reducing overhydration complications, though this requires further validation 3.
Patient age and body surface area predict delayed clearance in cycle 1, but hyperhydration mitigates these risk factors in subsequent cycles by improving renal elimination 2.
Practical Implementation
Hydration should begin 4 hours before methotrexate infusion and continue throughout the infusion and post-infusion period until methotrexate levels fall below 0.1 µmol/L 5, 3.
Monitor serum creatinine and methotrexate levels at 24,42, and 48 hours to detect delayed clearance early and adjust hydration accordingly 2.
For patients experiencing ≥50% increase in plasma creatinine or delayed methotrexate clearance, escalate to 200 mL/m²/hour hydration rate in subsequent cycles 5, 2.