Epidemiologic Characteristics of Acute Kidney Injury During Cisplatin Infusions in Children Treated for Cancer

Abstract

IMPORTANCE Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. OBJECTIVE To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study examined children (aged <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 2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. EXPOSURES Cisplatin infusions. MAIN OUTCOMES AND MEASURES The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteriabased 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. RESULTS 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).

Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer

“…In agreement with previous reports, the rate of SCr‐AKI in our study was 25% 2,3,6,8,39 . As we previously reported, eAKI occurred in most children 34 . As expected, urine platinum was weakly associated with cisplatin dose.…”

“…The Epidemiology Coordinating and Research Center (Edmonton) provided centralized recruitment; entered data into a secure, online Research Electronic Data Capture database; and performed regular site queries. Throughout‐study and end‐of‐study queries were performed to minimize missing data and maximize accuracy of the data 33,34,36 …”

“…33 The ABLE study design has been previously described. 33,34 Inclusion criteria were age <18 years at cancer diagnosis and initiation of cisplatin treatment, with at most 1 completed cisplatin cycle. Exclusion criteria were measured or estimated GFR (eGFR) <30 mL/min/1.73m 2 or kidney transplantation before cis-platin initiation.…”

A Micellar Formulation of Quercetin Prevents Cisplatin Nephrotoxicity

“…At the subcellular and molecular levels, cisplatin tubular cytotoxicity is driven by mitochondrial injury, which curtails respiration, produces oxidative stress, and induces apoptotic and necrotic cell death and a deleterious inflammatory response [ 13 , 15 , 16 ]. Oxidative stress is recognized as a central mechanism of cisplatin cytotoxicity and nephrotoxicity [ 12 , 13 , 15 , 16 , 17 ], arising from an increased production of reactive oxygen species and a weakened endogenous antioxidant enzyme barrier [ 5 , 7 , 18 ].…”

Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney Injury

“…However, the relative proportions of C-AKI across various equations were not profoundly different for two possible reasons: First, baseline kidney function by eGFR or eCrCl alone has not been consistently shown to predict C-AKI. [36][37][38][39][40][41] Second, our cohort, despite being very large and inclusive, did not have many patients with very low eGFR (ie, patients who would presumably be at highest risk of C-AKI). The mean eGFRCKD-EPI in the <60 ml/min/1.73 m 2 group was 51.3 ml/min/1.73 m 2 .…”