br Methods br We performed a retrospective review of
We performed a retrospective review of the electronic medical records of Seoul National University Hospital, Seoul, South Korea, with approval by the institutional review board (No. H-1509-051-702). This analysis included patients who were diagnosed with cancer between January 1, 2004 and December 31, 2013. Patients who were younger than 18 years at cancer diagnosis and who had creatinine (Cr) levels measured at least twice in the first year after diagnosis were eligible. Patients who had previously been diagnosed with CKD with an initial estimated glomerular filtration rate (eGFR) of lower than 15 mL/minute/1.73 m2 or who had previously received renal replacement therapy (RRT) were not eligible.
The following clinical data were collected: initial blood test results, all available serum Cr levels and urinalysis, development of TLS, performance of nephrectomy as a part of cancer treatment, use of contrast for computed tomography (CT) scans, use of RRT such as intermittent hemodialysis, and continuous RRT. Data on cancer treatment were also collected, including chemotherapy, overall duration of chemotherapy treatment, administra-tion of 5 chemotherapeutic agents that are widely used in children and are known to be nephrotoxic (carboplatin, cisplatin, cyclophosphamide, ifosfamide, and metho-trexate), administration of high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT), and treatment outcome of cancer. Mortality data were ob-tained from both the institutional electronic medical re-cord and the Vital Statistics reported on July 2016 by the Statistics Korea, a governmental organization for na-tional statistics.
Definitions and Measurements
Cancer types of the patients were categorized into 7 groups: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), lymphoma, neuroblastoma (NBL), Wilms tumor, Norfloxacin tumor (including medulloblastoma, primitive neuroectodermal tumor, intracranial germ cell tumor, and
other brain tumors), and other cancers (including retinoblastoma, hepatoblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, nonrhabdomyosarcoma soft tissue sarcoma, extracranial germ cell tumor, and other unspecified cancers).
AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria with some modifications.20 Stage 1 AKI was defined as a rise of Cr by 0.3 mg/dL in 2 days or by 1.5 times in 7 days, stage 2 as a rise of Cr by 2 times, and stage 3 as a rise of Cr above 4 mg/dL or by 3 times. Cr had to be at least 0.5 mg/dL for the patients to be diagnosed with AKI when the
fold-change criterion was used, to avoid over-diagnosis in young patients whose baseline Cr values were low.22,23
When the Cr at presentation was high, a recovery of Cr by more than 50% or by 0.3 mg/dL was used for the diagnosis of AKI, as proposed in the KDIGO criteria. For the purpose of this study, the application of RRT was not used as a criterion of stage 3 AKI because it is often transiently used for prompt management of TLS or toxic methotrexate levels in children with cancer, even without presumable actual renal dysfunction. In addition, the criterion concerning the urine output could not be used because of the retrospective nature of this study. Data on maximum AKI stage, number of AKI episodes, and time from cancer diagnosis to AKI were obtained. Deterioration of renal functions in the timeframe of 4 weeks from the onset of AKI was considered a single episode.
Serum Cr level measured either 1 year after the completion of cancer therapy or 5 years after the initial diagnosis was used as the final Cr to determine the long-term renal outcome. Final eGFRs of survivors were estimated with the CKD in Children “bedside Schwartz” equation, using their final serum Cr level and their height at the time of Cr measurement.24 For patients age 18 years or older at final Cr measurement, the CKD Epidemiology Collaboration equation was used to estimate the eGFR.25 A final eGFR of less than 90 mL/minute/1.73 m2 was defined as impaired renal function. An albumin dipstick test result of greater than 1+ on at least 2 occasions at the time of final serum Cr measurement was defined as proteinuria.