Long-Term Kidney Outcomes in Paediatric Osteosarcoma Survivors: A 20-Year Multi-Centre Study

Background: The long-term kidney outcomes in paediatric osteosarcoma survivors treated with nephrotoxic chemotherapeutic agents are not well-described. Methods: We conducted a multi-centre retrospective cohort study and recruited paediatric osteosarcoma survivors who survived beyond 5 years from cancer diagnosis over a 20-year period. Chronic kidney disease (CKD) was defined as evidence of kidney impairment, chronic tubulopathy, and proteinuria upon last follow-up. Results: We included 89 patients (57% males) with a mean follow-up period of 14.9 years. A total of 42 subjects (47.2%) developed CKD, 28 of whom had CKD stage 1 with either chronic tubulopathy or proteinuria; 14 patients had CKD stage 2 (eGFR < 90 mL/min/1.73 m2), while two had CKD stage 3 (eGFR < 60 mL/min/1.73 m2). Chronic tubular dysfunction was reported in 34 patients (38%), with hypomagnesemia being the most common manifestation. Proteinuria and hypertension were infrequently observed, in 3% and 8% of cases, respectively. We found that a history of severe AKI and aminoglycoside exposure during the treatment course were significant risk factors for CKD, but the dose-dependent relationships between the development of CKD and cisplatin, ifosfamide, and methotrexate could not be demonstrated. Conclusions: CKD is prevalent among paediatric osteosarcoma survivors. Caution is needed when using multiple nephrotoxic agents at the same time, as this could increase the risk of CKD in the long run. Multi-disciplinary regular surveillance should be performed to identify and manage CKD early, including kidney function, electrolyte, and proteinuria monitoring.