Long-term renal follow-up of children treated with cisplatin, carboplatin, or ifosfamide: a pilot study
Childhood cancer survivors treated with cisplatin, ifosfamide, or carboplatin are at risk for late kidney and blood pressure (BP) abnormalities. Few studies have comprehensively evaluated kidney outcomes and 24-h ambulatory BP monitoring (ABPM) in this population. We aimed to describe chemotherapy-associated acute kidney injury (AKI) and late kidney outcomes using standardized definitions.
This was a single-center longitudinal pilot study of 23 children who participated in a previous study during cisplatin, carboplatin, or ifosfamide treatment. Medical charts were reviewed retrospectively. Available patients were approached for a study visit for blood and urine collection, BP measurement, and ABPM. AKI is defined by serum creatinine (SCr) rise (Kidney Disease: Improving Global Outcomes definition [SCr-AKI]). Electrolyte-AKI is defined by hypokalemia, hypophosphatemia, or hypomagnesemia. Chronic kidney disease (CKD) is defined by estimated glomerular filtration rate < 90 mL/min/1.73 m2, albuminuria, or proteinuria. Electrolyte-CKD is defined by low serum electrolyte concentration or electrolyte supplementation.
Median age at chemotherapy start was 8.3 years; 9/23 (39%) were boys. Fourteen out of 23 (61%) patients had SCr-AKI during therapy; all developed electrolyte-AKI. Median 5.7 years post-chemotherapy, 7/22 (32%) had CKD, 11/23 (48%) had electrolyte-CKD, and 2/20 (10%) had hypertension. Fifteen out of 23 patients (65%) had either CKD, electrolyte-CKD, or hypertension. In ten patients available for a study visit (median 4.9 years post-chemotherapy), 1/10 (10%) had hypertension by ABPM; none had masked or white coat hypertension. All ten had at least one kidney abnormality (CKD, electrolyte-CKD, office pre-hypertension, or abnormal ABPM).
Using standardized outcome definitions, children treated with cisplatin, carboplatin, or ifosfamide have a high prevalence of late kidney abnormalities. Research must elucidate best practice for post-cancer treatment follow-up and kidney complication treatment.
KeywordsChemotherapy Pediatric Acute kidney injury Chronic kidney disease Hypertension
We would like to acknowledge the work performed by all study staff for specimen and data collection. A special thank you goes to study participants and their families.
This work was supported by grants from the Fonds de recherche du Québec - Santé (FRQS) and the Kidney Research Scientist Core Education and National Training Program (KRESCENT) awarded to Michael Zappitelli. A FRQS Doctoral Training Scholarship awarded to Kelly McMahon also helped support this work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For the retrospective study component, formal consent was not required.
Informed consent was obtained from all individual participants included in the study.
- 2.Phillips SM, Padgett LS, Leisenring WM, Stratton KK, Bishop K, Krull KR, Alfano CM, Gibson TM, de Moor JS, Hartigan DB, Armstrong GT, Robison LL, Rowland JH, Oeffinger KC, Mariotto AB (2015) Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomark Prev 24(4):653–663CrossRefGoogle Scholar
- 8.Knijnenburg SL, Mulder RL, Schouten-Van Meeteren AY, Bokenkamp A, Blufpand H, van Dulmen-den Broeder E, Veening MA, Kremer LC, Jaspers MW (2013) Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev 10(10):CD008944Google Scholar
- 9.Sterling M, Al-Ismaili Z, McMahon KR, Piccioni M, Pizzi M, Mottes T, Lands LC, Abish S, Fleming AJ, Bennett MR, Palijan A, Devarajan P, Goldstein SL, O'Brien MM, Zappitelli M (2017) Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy. Pediatr Blood Cancer 64(10). https://doi.org/10.1002/pbc.26538 CrossRefGoogle Scholar
- 11.Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury (2012). Kidney Int, Suppl 2 (1):1–138Google Scholar
- 12.Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. (2010) National Institutes of Health. National Cancer Institute. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed 29 Aug 2017
- 14.CDC Growth Charts. (2000) Centers for Disease Control and Prevention/ National Center for Health Statistics. http://www.cdc.gov/growthcharts/. Accessed 29 Aug 2017
- 15.National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents (2004). Pediatrics 114 (Supplement 2):555–576Google Scholar
- 18.Flynn JT, Daniels SR, Hayman LL, Maahs DM, BW MC, Mitsnefes M, Zachariah JP, Urbina EM, American Heart Association Atherosclerosis H, Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young (2014) Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension 63(5):1116–1135CrossRefGoogle Scholar
- 19.O'Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P, European Society of Hypertension Working Group on Blood Pressure M (2003) European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. J Hypertens 21(5):821–848CrossRefGoogle Scholar
- 22.Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ (2005) Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation 111(5):697–716CrossRefGoogle Scholar
- 23.Daskalopoulou SS, Rabi DM, Zarnke KB, Dasgupta K, Nerenberg K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, McKay DW, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallee M, Ramesh Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Brian Penner S, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Stone JA, Drouin D, Lavoie KL, Hamet P, Fodor G, Gregoire JC, Fournier A, Lewanczuk R, Dresser GK, Sharma M, Reid D, Benoit G, Feber J, Harris KC, Poirier L, Padwal RS (2015) The 2015 Canadian hypertension education program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 31(5):549–568CrossRefGoogle Scholar
- 25.Knijnenburg SL, Jaspers MW, van der Pal HJ, Schouten-van Meeteren AY, Bouts AH, Lieverst JA, Bökenkamp A, Koning CCE, Oldenburger F, Wilde JCH, van Leeuwen FE, Caron HN, Kremer LC (2012) Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors. Clin J Am Soc Nephrol 7(9):1416–1427CrossRefGoogle Scholar