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Proteinuria due to suboptimal hydration with high-dose methotrexate therapy
1Second Department of Pediatrics, Semmelweis Medical School, Budapest, Hungary.
Insights
High-dose methotrexate (HDMTX) can cause kidney damage. Modifying hydration and urinary alkalization protocols significantly reduced proteinuria in children receiving HDMTX for cancer treatment.
Area of Science:
- Pediatric Oncology
- Nephrology
- Pharmacology
Background:
- High-dose methotrexate (HDMTX) is a critical chemotherapy agent for pediatric malignancies.
- Renal damage, manifesting as proteinuria, is a significant complication of HDMTX therapy.
- Previous protocols for managing HDMTX-induced nephrotoxicity were suboptimal.
Purpose of the Study:
- To investigate the incidence of proteinuria following HDMTX administration in pediatric cancer patients.
- To evaluate the efficacy of a modified hydration and urinary alkalization protocol in preventing HDMTX-induced renal damage.
Main Methods:
- Retrospective analysis of 52 HDMTX courses in 24 children (1989-1990) with a standard hydration/alkalization protocol.
- Prospective evaluation of 24 children (1991-1992) with a modified intensive intravenous prehydration and posthydration protocol including sodium bicarbonate.
- Urine protein levels were measured pre-treatment, and on days 1 and 2 post-infusion.
Main Results:
- The initial protocol showed a significant increase in proteinuria (mean 0.38 g/m2 on day 1, 0.39 g/m2 on day 2) in 54% of patients.
- The modified protocol resulted in significantly lower mean proteinuria levels (0.05 g/m2 on day 1, 0.08 g/m2 on day 2), all within normal ranges.
- Statistical analysis confirmed a significant difference between the two protocols (P < 0.05).
Conclusions:
- Standard hydration and alkalization are insufficient to prevent HDMTX-induced proteinuria in children.
- An intensive intravenous hydration and urinary alkalization regimen effectively mitigates proteinuria associated with HDMTX therapy.
- This modified approach is crucial for preventing renal complications in pediatric patients undergoing HDMTX treatment.
Abstract:
One of the major complications after high-dose methotrexate (HDMTX) infusions is renal damage. We investigated the occurrence of proteinuria after HDMTX administration in children with pediatric malignancies (acute lymphoid leukaemia, osteosarcoma Burkitt's lymphoma). In the period 1989-1990 we gave 52 HDMTX courses to 24 children. During this period, prehydration and extra urinary alkalisation were performed only if the urinary specific gravity was over 1010 or if the urinary pH fell below 7. Using this schedule the mean values obtained for protein extraction were: before the therapy, 0.12 +/- 0.03 g/m2; on day 1 after MTX treatment, 0.38 +/- 0.06 g/m2; and on day 2 after the MTX infusion, 0.39 +/- 0.11 g/m2 (P < 0.01). A significant increase in proteinuria (> 0.2 g/m2 post- vs pretreatment) was detectable in 54% of the patients. In the period 1991-1992 we modified the hydration-alkalisation schedule to include i.v. prehydration for 18-24 h at 3 l/m2/day with a 0.45% NaCl-5% glucose solution along with sodium bicarbonate and posthydration for 72 h with the same solution. On this protocol the mean values determined for the urinary protein content were all in the normal range (pretreatment, 0.03 g/m2/day; day 1, 0.05 g/m2/day; and day 2, 0.08 g/m2/day). These findings were significantly different from the previous results (P < 0.05).