Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute kidney injury (AKI) typically within the first few days of exposure and is associated with short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage has progressed to functional impairment, when mitigation strategies are ineffective. Tests that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss would be very impactful, affording opportunities for prevention or early intervention to mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.

The field of metabolomics seeks to identify patterns of small molecules (metabolites) involved in cell or tissue metabolism related to disease states, or patient factors like lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can identify at-risk patients and reveal disease-related changes earlier than existing diagnostic methods do.

In CisP-treated children and adults from across Canada, we will identify urine and plasma metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable. Our identified biomarkers will allow individualization of CisP treatment based on the level of nephrotoxicity risk and the design of trials to mitigate the progression and complications of CisP nephrotoxicity.

Inclusion Criteria:

• Adult participants: Initiating treatment with CisP (≥75 mg/m2) for head/neck or lung cancers at one of the Adult participating sites; 18 years of age or older.
• Paediatric participants: Initiating treatment with CisP for any cancer diagnosis at one of the Pediatric participating sites; greater than 3 months of age.
• All participants: Consent to participate in the study.

Exclusion Criteria:

• Diagnosis of chronic kidney disease (CKD) at baseline (glomerular filtration rate <60 mL/min/1.73m2, determined by chart review of either formal glomerular filtration rate testing, 24 hour creatinine creatinine clearance of age-appropriate serum creatinine-based estimated glomerular filtration rate equations; past kidney transplant)
• Previous use of any nephrotoxic drugs included on the provided Excluded Nephrotoxic Medications list in the two weeks prior to initiation of CisP treatment
• Previous use of CisP
• Previous radiotherapy (total body irradiation or abdominal radiation only) in the last 1 month prior to study
• Previous hematopoietic stem cell transplant
• Any chronic or acute health condition that the investigator feels would render the patient inappropriate for this study, including but not limited to significant uncontrolled cardiorespiratory, hepatic, infectious, or renal disease at the discretion of the investigator

Child Cohort. We already performed these study procedures on 159 children in the "ABLE" study, a 12-centre cohort study.Eligibility criteria and data/samples collected on these patients during their initial CisP treatment are almost identical to the present study. The cohort diagnoses include neuroblastoma, medulloblastoma, osteosarcoma, germ cell tumour, hepatoblastoma, and other cancers. Data and specimens from the pediatric study subjects in the ABLE study who were recruited during their first CisP infusion (about half) will be included in the current study. The remaining children (to reach a target of 300) will be recruited over 3 years from the following centres: McGill, UBC, SickKids, U. Manitoba and UWO. Adult Cohort. 300 adults (18 years of age or older) initiating CisP (≥75 mg/m2) treatment for head/neck or lung cancers will be recruited to participate in this study from PMH (Toronto), UBC and UWO over 2 years. Over 500 new patients/year are available across all sites.