Renal vulnerability beyond glomerular filtration in heavily pre-treated children with relapsed/refractory pediatric solid tumors: A multidimensional clinical assessment

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is used in selected children with relapsed solid tumors. In heavily pre-treated children, cumulative nephrotoxic exposure, reduced renal mass, and tubular dysfunction may contribute to renal vulnerability that is not reflected by glomerular filtration rate (GFR) alone. Aims and Objectives: This study aimed to characterize renal vulnerability beyond GFR in heavily pre-treated children undergoing autologous HSCT and to explore a multidimensional assessment incorporating structural renal reserve, cumulative nephrotoxic exposure, glomerular function, and tubular phenotype. Materials and Methods: Three children with relapsed pediatric solid tumors underwent autologous HSCT following modified thiote-pamelphalan (TT–MEL) conditioning. We reviewed clinical records for renal anatomy, cumulative nephrotoxic treatment exposure, GFR, and tubular electrolyte abnormalities before and during transplantation. Results: We observed three distinct renal phenotypes despite preserved GFR. Case 1 had a solitary kidney, substantial platinum/ifosfamide exposure, and pre-existing mild hypomagnesemia and hypokalemia, followed by severe renal magnesium and potassium wasting during transplantation. Case 2 had a solitary kidney and substantial nephrotoxic exposure without documented tubular dysfunction. Case 3 had extensive platinum/ifosfamide exposure with preserved GFR and no documented dyselectrolytemia. All three received modified TT–MEL and achieved timely engraftment without dialysis. Conclusion: Renal vulnerability may extend beyond a measurable reduction in GFR. Assessment of structural renal reserve, cumulative nephrotoxic exposure and tubular phenotype may complement conventional GFR-based assessment before high-dose conditioning. These observations support a conceptual multidimensional model requiring prospective validation.