Pediatr Nephrol (2014) 29:2421–2424 DOI 10.1007/s00467-014-2935-z

BRIEF REPORT

Cisplatinum nephrotoxicity in oncology therapeutics: retrospective review of patients treated between 2005 and 2012 Morgan Finkel & Adam Goldstein & Yael Steinberg & Linda Granowetter & Howard Trachtman

Received: 12 May 2014 / Revised: 22 July 2014 / Accepted: 25 July 2014 / Published online: 30 August 2014 # IPNA 2014

Abstract Background Cisplatinum (CP) is associated with acute kidney injury. The aim of this study was to define the spectrum of CPinduced nephrotoxicity in current practice. Case-Diagnosis/Treatment A single-center, retrospective chart review was performed on children who received CP for treatment of a malignancy at the Hassenfeld Children’s Center for Blood and Cancer Disorders of NYU Langone Medical Center between 2005 and 2012. Patients were considered to have nephrotoxicity if they had: (1) a decrease in estimated glomerular filtration rate (eGFR) of ≥30 % or (2) a decline in serum magnesium of ≥0.2 meq/L or (3) a decline in serum potassium of ≥0.2 meq/L. Thirty-two patients (mean age 8.0±7.0 years) were included in this review, of whom 21 had a brain tumor (BT) and 11 had an osteosarcoma (OS); 31 (97 %) of the patients had a disturbance in renal function. The mean reduction in eGFR, serum magnesium and potassium was 37±17, 30±16 and 25±14 %, respectively. The decline in eGFR, hypomagnesemia and hypokalemia was persistent in 38, 60 and 40 % of cases, respectively, through the short-term follow-up period. No patients required dialysis.

Electronic supplementary material The online version of this article (doi:10.1007/s00467-014-2935-z) contains supplementary material, which is available to authorized users. M. Finkel : A. Goldstein : Y. Steinberg : H. Trachtman Division of Nephrology, Department of Pediatrics, NYU Langone Medical Center, New York, NY, USA

Conclusions Nearly all patients receiving CP in current care experience modest glomerular and tubular injury. The abnormalities persist in 40–60 % of cases during the short-term recovery period after CP treatment.

Introduction Cisplatinum (CP) is a chemotherapeutic alkylating agent that is prescribed for the treatment of various malignancies [1, 2]. Its use is limited by serious adverse events, including nephrotoxicity [3]. Past studies have revealed that 30–60 % of pediatric patients treated with CP develop some degree of nephrotoxicity [3–7]. However, most studies represent the outcomes of children who were treated for cancer primarily during the 1990s, with more recent reports limited by relatively small sample sizes. Updated information on the impact of CP therapy would help clarify the extent of the nephrotoxicity experienced by pediatric patients under current standards of care. Such information includes a greater awareness of CP nephrotoxicity, meticulous attention to hydration status and use of mannitol to maintain diuresis, improved monitoring of nephrotoxic drugs and use of alternative therapies with a decreased adverse effect on kidney function. We have therefore conducted this single-center, retrospective chart review of children and adolescents who received CP as part of a chemotherapeutic regimen to treat an osteosarcoma (OS) or a brain tumor (BT) during the period 2005–2012 to define the spectrum of CP nephrotoxicity in current practice.

L. Granowetter Division of Hematology–Oncology, Department of Pediatrics, NYU Langone Medical Center, New York, NY, USA

Patients and methods

H. Trachtman (*) Clinical and Translational Science Institute (CTSI), NYU Langone Medical Center, 227 East 30th Street, New York, NY 10016, USA e-mail: [email protected]

A retrospective chart review was performed on children who received at least one course of CP for treatment of a malignancy in the Division of Pediatric Hematology/Oncology at the Hassenfeld Children’s Center of NYU Langone Medical

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Center during the years 2005–2012. This time period represents a convenience sample, based on access to complete medical records. The chemotherapy regimen for each CP dose was similar for patients with OS or BT and the protocols were stable with few procedural changes during the study period. For OS patients, the CP dose in each course was 60 mg/m2 per day on 2 consecutive days. The BT patients received 75 mg/m2 CP for 1 day. Body surface area (BSA) was calculated using the Dubois formula. The regimen involved prehydration with dextrose 5 % water/0.45 % normal saline (D5W 0.45 % NS) + 20 mEq KCl and 250 mg MgSO4 per liter until urine specific gravity was ≤1.010, followed by mannitol 10 g/m2 in 500 mL/m2 of NS over 2 h. CP was then infused in 1,000 mL/m2 of NS with 10 g/m2 of mannitol over 4 h for OS patients or 6 h for BT patients. After completion of the CP/mannitol infusion, D5W 0.45 %NS+20 mEq KCl and 250 mg MgSO4 per liter was infused at 125 mL/m2 per hour for at least 16 h. Furosemide and other diuretics were not prescribed by protocol and their use was discouraged. Diet was not altered and food intake was not recorded during CP treatment. The following data were collected and tabulated: age at diagnosis, tumor type, number of courses and cumulative CP dose. Serum creatinine, magnesium (Mg), and potassium (K) levels were recorded prior to CP treatment, at the nadir of kidney function during treatment, and 1–3 weeks after the last course of CP, based on the availability of laboratory data in the medical record. Estimated glomerular filtration rate (eGFR) was calculated using the revised Schwartz formula [8]. The Cockcroft–Gault equation was used to estimate GFR in three patients who were aged ≥18 years. Patients were considered to have developed CP nephrotoxicity if they had: (1) a decrease in eGFR of ≥30 % or (2) a decline in serum Mg concentration of ≥0.2 meq/L or (3) a decline in serum K concentration of ≥0.2 meq/L. These criteria were designed specifically for this study and were intended to capture clinically meaningful changes in GFR and to apply one standard for the two electrolytes. The definition of hypokalemia is similar to that used to assess response to various treatments in patients with Gitelman syndrome [9]. A patient was considered to have achieved full recovery if the final assessment after completion of CP indicated that their renal function or serum Mg or K concentration had returned to at least 90 % of the baseline value. All laboratory testing was performed in the clinical chemistry laboratory of NYU Langone Medical Center. All of the data were normally distributed, and initial, nadir and final eGFR, Mg and K were compared using a paired t test. Linear regression was used to analyze the relationships between CP dosage and the various aspects of kidney function. This retrospective chart review was approved by the Institutional Review Board of New York University Langone Medical Center.

Pediatr Nephrol (2014) 29:2421–2424

Results Patients Electronic Supplementary Material (ESM) Fig. 1 summarizes the flow chart of the screening process, beginning with a survey of children maintained in a clinical trial listing who might have received CP, reasons for exclusion and the final study population. During the study period, there were 53 patients with a new diagnosis of BT or OS. Of these, 32 patients (age 8.0±7.0 years, median age 5.7 years, range 0.12–27.25 years) were included in this review: 21 with BT and 11 with OS. OS patients were older (15.5±6.0 vs. 4.1± 3.2 years; P

Cisplatinum nephrotoxicity in oncology therapeutics: retrospective review of patients treated between 2005 and 2012.

Cisplatinum (CP) is associated with acute kidney injury. The aim of this study was to define the spectrum of CP-induced nephrotoxicity in current prac...
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