Epidemiologic Characteristics of Acute Kidney Injury During Cisplatin Infusions in Children Treated for Cancer
Authors: Kelly R. McMahon, Shahrad Rod Rassekh, Kirk R. Schultz, Tom Blydt-Hansen, Geoffrey D. E. Cuvelier, Cherry Mammen, Maury Pinsk, Bruce C. Carleton, Ross T. Tsuyuki, Colin J. D. Ross, Ana Palijan, Louis Huynh, Mariya Yordanova, Frédérik Crépeau-Hubert, Stella Wang, Debbie Boyko, Michael Zappitelli
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. <h3>Objective</h3> To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. <h3>Design, Setting, and Participants</h3> This prospective cohort study examined children (aged &lt;18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m<sup>2</sup>or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. <h3>Exposures</h3> Cisplatin infusions. <h3>Main Outcomes and Measures</h3> The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria–based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. <h3>Results</h3> A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). <h3>Conclusions and Relevance</h3> The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.