Discussion
Our study found that half of our childhood AML patients developed acute kidney injury during their course of chemotherapy. AKI most commonly occurs in the early stages after the beginning of treatment, with a median time to first episode within one month of treatment initiation. Age at diagnosis ≥ 10 years, impaired renal function at AML diagnosis, and septic shock were independent risk factors for AKI.
Pediatric data on the epidemiology of AKI in AML are limited, to our knowledge, to only two previous reports.10,19 In one study, the incidence of acute renal failure was found to be 16.2%19; however, since acute renal failure does not include severe cases of AKI, the incidence of AKI may have been underreported. The high incidence of AKI found in our study is consistent with a study by Du Plessis et al, who also used the KDIGO criteria for defining AKI.10
In studies in both adulthood and childhood AML, one of the common findings was that older age (more than 10 years in children and more than 55-60 years in adults) was a significant independent risk factor for AKI.10,19–21 These results correlated with the finding of other studies which found that the prognosis of AML gets worse with increasing age.22,23
We also found impaired initial renal function was strongly associated with a higher likelihood of one or more AKI incidents during admission in our study, consistent with a previous report in pediatric cancer patients from Korea.1 We found 15 AML patients with impaired initial eGFR at their first AML diagnosis, 12 of whom developed at least 1 episode of AKI. There were no significant differences in white blood cell counts or occurrence of tumor lysis syndrome that may have contributed to kidney damage between patients with impaired eGFR and patients with normal initial renal function. None of the patients in our study had had previous investigations for preexisting renal tract anomalies, so we did not know the exact cause of impaired renal function in these patients. However, due to the high risk of developing AKI in impaired renal function patients, nephrotoxic medications should only be prescribed with caution and renal function should be closely monitored during treatment in these patients.
Regarding infections, the most common treatment-related toxicity and main cause of death was sepsis, which has been commonly associated with AKI in both noncancer and cancer patients.8,24–26 Our study confirmed a strong association between septic shock and AKI during the course of chemotherapy, consistent with a previous pediatric AML study.10 In terms of overall treatment outcomes in our study, the proportion of patients entering remission was significantly lower in the AKI group. This finding might be explained by a dose adjustment of chemotherapy in patients who developed AKI. However, there were no differences in either relapse or mortality rates between the two groups. As the only known effective regimens for treating childhood AML involve aggressive treatment, lowering the intensity of chemotherapy may be beneficial in some patients, as this should lead to a decrease in associated infections and subsequent organ dysfunction, including AKI, and hopefully lead to decreased mortality, which is often related to organ-failure caused by sepsis rather than AML itself.
In conclusion, half of our childhood AML patients developed AKI during their chemotherapy treatment. Age ≥ 10 years at diagnosis, impaired renal function before treatment, and septic shock were independent risk factors for developing AKI.
Conflict of Interest Disclosure: The authors have no conflicts of interest relevant to this article to disclose.