Download or read book Cisplatin Nephrotoxicity in Children Treated for Cancer written by Kelly McMahon and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Cisplatin, a chemotherapy commonly used to treat pediatric solid tumours, causes acute kidney injury (AKI) and may lead to chronic kidney disease (CKD) and hypertension in children. The epidemiology of cisplatin-associated AKI, CKD, and hypertension, and the extent to which AKI associates with post-cancer kidney health in children treated with cisplatin is not clear. This doctoral thesis is comprised of four manuscripts. Thesis manuscript #1 describes the design and methodology of the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity study, which is an ongoing prospective cohort study of children treated with cisplatin at twelve pediatric hospitals in Canada. Thesis manuscripts #2, #3, and #4 report on the results of the ABLE Nephrotoxicity study. Study participants were free of severe kidney disease before initiating cisplatin therapy. Participants were studied at two cisplatin cycles during cancer treatment (at early [first or second cisplatin cycle] and late [last or second-to-last cycle] cisplatin infusions) and at three months after completing cisplatin therapy. Thesis manuscript #2 aims to describe the epidemiology and risk factors of AKI at individual cisplatin infusions. AKI at early and late cisplatin infusions was defined in two ways: a) Serum creatinine (SCr)-AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) SCr definition (≥stage 1); b) Electrolyte-AKI (eAKI): low serum magnesium, phosphate, or potassium (≥grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0). A total of 159 children (mean [standard deviation [SD]]: 7.2 [5.3] years; 80 [50%] male) participated. SCr-AKI occurred in 48/159 (30%) at early cisplatin infusions and in 23/143 (16%) at late cisplatin infusions; eAKI occurred in 106/159 (67%) at early cisplatin infusions and in 100/143 (70%) at late cisplatin infusions. In multivariable analyses, cancer type and pre-infusion kidney function were associated with SCr-AKI at early and late cisplatin infusions, and cisplatin dose was associated with SCr-AKI at late infusions. Thesis manuscript #3 aims to determine whether kidney tubular injury markers, urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1), are associated with and are early biomarkers of AKI. uNGAL and uKIM-1 were measured pre-cisplatin infusion, morning post-infusion, and near hospital discharge. SCr-AKI at individual cisplatin infusions was defined based on the KDIGO definition (≥stage 1). We found uNGAL and uKIM-1 concentrations were significantly higher in patients with vs. without SCr-AKI. These markers modestly discriminated for AKI at best (area under receiver-operating characteristic curve [AUC-ROC] range: 0.48-0.75); biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROCs range: 0.54-0.75) vs. early cisplatin infusions (AUC-ROCs range: 0.48-0.65). Thesis manuscript #4 aims to: 1) describe the epidemiology of AKI throughout entire cisplatin therapy, 2) describe the incidence of CKD and hypertension at three months post-cisplatin, 3) determine whether AKI during cisplatin therapy is associated with CKD or hypertension at three months post-treatment. Exposures during cisplatin therapy: a) SCr-AKI: KDIGO SCr definition (≥stage 1); b) Severe eAKI: ≥grade 3 eAKI by NCI CTCAE v4.0. Three-month outcomes evaluated: a) CKD: if age >2 years, estimated glomerular filtration rate (eGFR)