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Meta-Analysis
. 2019 Mar 11;3(3):CD008944.
doi: 10.1002/14651858.CD008944.pub3.

Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer

Esmee Cm Kooijmans  1 , Arend Bökenkamp, Nic S Tjahjadi, Jesse M Tettero, Eline van Dulmen-den Broeder, Helena Jh van der Pal, Margreet A Veening
Affiliations
Meta-Analysis

Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer

Esmee Cm Kooijmans et al. Cochrane Database Syst Rev. .

Abstract

Background: Improvements in diagnostics and treatment for paediatric malignancies resulted in a major increase in survival. However, childhood cancer survivors (CCS) are at risk of developing adverse effects caused by multimodal treatment for their malignancy. Nephrotoxicity is a known side effect of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate (GFR) impairment, proteinuria, tubulopathy, and hypertension. Evidence about the long-term effects of these treatments on renal function remains inconclusive. It is important to know the risk of, and risk factors for, early and late adverse renal effects, so that ultimately treatment and screening protocols can be adjusted. This review is an update of a previously published Cochrane Review.

Objectives: To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with the general population or CCS treated without potentially nephrotoxic treatment. In addition, to evaluate evidence on associated risk factors, such as follow-up duration, age at time of diagnosis and treatment combinations, as well as the effect of doses.

Search methods: On 31 March 2017 we searched the following electronic databases: CENTRAL, MEDLINE and Embase. In addition, we screened reference lists of relevant studies and we searched the congress proceedings of the International Society of Pediatric Oncology (SIOP) and The American Society of Pediatric Hematology/Oncology (ASPHO) from 2010 to 2016/2017.

Selection criteria: Except for case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment), in CCS treated before the age of 21 years with cisplatin, carboplatin, ifosfamide, radiation involving the kidney region, a nephrectomy, or a combination of two or more of these treatments. When not all treatment modalities were described or the study group of interest was unclear, a study was not eligible for the evaluation of prevalence. We still included it for the assessment of risk factors if it had performed a multivariable analysis.

Data collection and analysis: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction using standardised data collection forms. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.

Main results: Apart from the remaining 37 studies included from the original review, the search resulted in the inclusion of 24 new studies. In total, we included 61 studies; 46 for prevalence, six for both prevalence and risk factors, and nine not meeting the inclusion criteria, but assessing risk factors. The 52 studies evaluating the prevalence of renal dysfunction included 13,327 participants of interest, of whom at least 4499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0% to 84%. This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow-up duration and the methodological quality of available evidence.Seven out of 52 studies, including 244 participants, reported the prevalence of chronic kidney disease, which ranged from 2.4% to 32%.Of these 52 studies, 36 studied a decreased (estimated) GFR, including at least 432 CCS, and found it was present in 0% to 73.7% of participants. One eligible study reported an increased risk of glomerular dysfunction after concomitant treatment with aminoglycosides and vancomycin in CCS receiving total body irradiation (TBI). Four non-eligible studies assessing a total cohort of CCS, found nephrectomy and (high-dose (HD)) ifosfamide as risk factors for decreased GFR. The majority also reported cisplatin as a risk factor. In addition, two non-eligible studies showed an association of a longer follow-up period with glomerular dysfunction.Twenty-two out of 52 studies, including 851 participants, studied proteinuria, which was present in 3.5% to 84% of participants. Risk factors, analysed by three non-eligible studies, included HD cisplatin, (HD) ifosfamide, TBI, and a combination of nephrectomy and abdominal radiotherapy. However, studies were contradictory and incomparable.Eleven out of 52 studies assessed hypophosphataemia or tubular phosphate reabsorption (TPR), or both. Prevalence ranged between 0% and 36.8% for hypophosphataemia in 287 participants, and from 0% to 62.5% for impaired TPR in 246 participants. One non-eligible study investigated risk factors for hypophosphataemia, but could not find any association.Four out of 52 studies, including 128 CCS, assessed the prevalence of hypomagnesaemia, which ranged between 13.2% and 28.6%. Both non-eligible studies investigating risk factors identified cisplatin as a risk factor. Carboplatin, nephrectomy and follow-up time were other reported risk factors.The prevalence of hypertension ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and abdominal radiotherapy. A non-eligible study also found long follow-up time as risk factor. Three non-eligible studies showed that a higher body mass index increased the risk of hypertension. Treatment-related risk factors were abdominal radiotherapy and TBI, but studies were inconsistent.Because of the profound heterogeneity of the studies, it was not possible to perform meta-analyses. Risk of bias was present in all studies.

Authors' conclusions: The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow-up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment-related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large prospective cohort studies with adequate control groups when possible. In addition, these studies should deploy multivariable risk factor analyses to correct for possible confounding. Next to research concerning known nephrotoxic therapies, exploring nephrotoxicity after new therapeutic agents is advised for future studies. Until more evidence becomes available, CCS should preferably be enrolled into long-term follow-up programmes to monitor their renal function and blood pressure.

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Conflict of interest statement

Esmee CM Kooijmans: none known

Arend Bökenkamp: none known

Nic S Tjahjadi: none known

Jesse M Tettero: none known

Eline van Dulmen‐den Broeder: none known

Heleen van der Pal is author of several studies included in this review (i.e. Mulder 2013 and Knijnenburg 2012).

Margreet A Veening: none known

Figures

1
1
Study flow diagram aStudies that did not fulfil the inclusion criteria, but performed multivariable risk analyses
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.1, chronic kidney disease/renal insufficiency as defined by study authors. It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
5
5
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.2, (estimated) glomerular filtration rate < 90 mL/min/1.73m². It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
6
6
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.3, (estimated) glomerular filtration rate < 80 mL/min/1.73 m². It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
7
7
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.4 (estimated) glomerular filtration rate < 75 mL/min/1.73m²
8
8
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.5, (estimated) glomerular filtration rate < 70 mL/min/1.73 m²
9
9
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.6, (estimated) glomerular filtration rate < 60 mL/min/1.73m². It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
10
10
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome, 1.7 (estimated) glomerular filtration rate: other definition or definition not mentioned
11
11
Forest plot of comparison 2. Mean glomerular filtration rate in mL/min/1.73 m² at least 1 year after diagnosis, outcome 2.1, mean (estimated) glomerular filtration rate in studies that included internal or healthy controls
12
12
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.7, proteinuria as defined by study authors. It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
13
13
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.8, serum phosphate/hypophosphataemia as defined by study authors. It should be noted that the method used in Reviw Manager to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
14
14
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.9, tubular phosphate regulation parameters as defined by study authors
15
15
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.10, serum magnesium/hypomagnesaemia as defined by study authors
16
16
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.11, blood pressure. It should be noted that the method used in Review Manager 5 to calculate 95% confidence intervals is not accurate in percentages close to 0, leading to confidence intervals that are below 0%
17
17
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.13, composite outcome as defined by Weirich 2004
18
18
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome:1.14, composite outcome as defined by Oue 2014
19
19
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.15, composite outcome as defined by Stohr 2007b
20
20
Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.16, composite outcome as defined by von Schweinitz 1997
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Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.17, composite outcome as defined by Schiavetti 2015a
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Forest plot of comparison 1. Prevalence of renal dysfunction, outcome 1.18, composite outcome as defined by Van Dijk 2010
1.1
1.1. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 1 Chronic kidney disease/renal insufficiency as defined by study authors.
1.2
1.2. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 2 (Estimated) glomerular filtration rate < 90 mL/min/1.73m².
1.3
1.3. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 3 (Estimated) glomerular filtration rate < 80 mL/min/1.73m².
1.4
1.4. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 4 (Estimated) glomerular filtration rate < 75 mL/min/1.73m².
1.5
1.5. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 5 (Estimated) glomerular filtration rate < 70 mL/min/1.73m².
1.6
1.6. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 6 (Estimated) glomerular filtration rate < 60 mL/min/1.73m².
1.7
1.7. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 7 (Estimated) glomerular filtration rate: other definition or definition not mentioned.
1.8
1.8. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 8 Proteinuria as defined by study authors.
1.9
1.9. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 9 Serum phosphate/hypophoshataemia as defined by study authors.
1.10
1.10. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 10 Tubular phosphate regulation parameters as defined by the study authors.
1.11
1.11. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 11 Serum magnesium/hypomagnesaemia as defined by study authors.
1.12
1.12. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 12 Blood pressure as defined by study authors.
1.13
1.13. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 13 Composite outcome as defined by Weirich 2004.
1.14
1.14. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 14 Composite outcome as defined by Oue 2014.
1.15
1.15. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 15 Composite outcome as defined by Stohr 2007b.
1.16
1.16. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 16 Composite outcome as defined by von Schweinitz 1997.
1.17
1.17. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 17 Composite outcome as defined by Schiavetti 2015a.
1.18
1.18. Analysis
Comparison 1 Prevalence of renal dysfunction, Outcome 18 Composite outcome as defined by Van Dijk 2010.
2.1
2.1. Analysis
Comparison 2 Mean (estimated) glomerular filtration rate in mL/min/1.73m² at least 1 year after diagnosis, Outcome 1 Mean (estimated) glomerular filtration rate in studies that included internal or healthy controls.
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    1. Dijk IW, Oldenburger F, Cardous‐Ubbink MC, Geenen MM, Heinen RC, Kraker J, et al. Evaluation of late adverse events in long‐term Wilms' tumor survivors. International Journal of Radiation Oncology Biology Physics 2010;78:370‐8. - PubMed
Van Why 1991 {published data only}
    1. Why SK, Friedman AL, Wei LJ, Hong R. Renal insufficiency after bone marrow transplantation in children. Bone Marrow Transplantation 1991;7(5):383‐8. - PubMed
von Schweinitz 1997 {published data only}
    1. Schweinitz D, Byrd DJ, Hecker H, Weinel P, Bode U, Burger D, et al. Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology. European Journal of Cancer 1997;33(8):1243‐9. - PubMed
Weirich 2004 {published data only}
    1. Weirich A, Ludwig R, Graf N, Abel U, Leuschner I, Vujanic GM, et al. Survival in nephroblastoma treated according to the trial and study SIOP‐9/GPOH with respect to relapse and morbidity. Annals of Oncology 2004;15(5):808‐20. - PubMed
Wikstad 1986 {published data only}
    1. Wikstad I, Pettersson BA, Elinder G, Sokucu S, Aperia A. A comparative study of size and function of the remnant kidney in patients nephrectomized in childhood for Wilms' tumor and hydronephrosis. Acta Paediatrica Scandinavia 1986;75(3):408‐14. - PubMed

References to studies excluded from this review

Abboud 2009 {published data only}
    1. Abboud I, Porcher R, Robin M, Latour RP, Glotz D, Socie G, et al. Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2009;15:1251‐7. - PubMed
Abd‐El‐Aal 2005 {published data only}
    1. Abd‐El‐Aal HH, Mokhtar MM, Habib EE, El‐Kashef AT, Fahmy ES. Medulloblastoma: conventional radiation therapy in comparison to chemo radiation therapy in the post‐operative treatment of high‐risk patients. Journal of the Egyptian National Cancer Institute 2005;17:301‐7. - PubMed
Abedi 1990 {published data only}
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Ahn 2013 {published data only}
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Aksnes 2009 {published data only}
    1. Aksnes LH, Bauer HC, Dahl AA, Fossa SD, Hjorth L, Jebsen N, et al. Health status at long‐term follow‐up in patients treated for extremity localized Ewing sarcoma or osteosarcoma: a Scandinavian Sarcoma Group study. Pediatric Blood and Cancer 2009;53:84‐9. - PubMed
Aleksa 2001 {published data only}
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Aleksa 2004 {published data only}
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Amato 1995 {published data only}
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Anderson 1979 {published data only}
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Anderson 2010 {published data only}
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Anderson 2016 {published data only}
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Antman 1989 {published data only}
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Arai 1998 {published data only}
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Arakelyan 2010 {published data only}
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Arga 2015 {published data only}
    1. Arga M, Oguz A, Pinarli FG, Karadeniz C, Citak EC, Emeksiz HC, et al. Risk factors for cisplatin‐induced long‐term nephrotoxicity in pediatric cancer survivors. Pediatrics International 2015;57:406‐13. - PubMed
Argueso 1992 {published data only}
    1. Argueso LR, Ritchey ML, Boyle ET Jr, Milliner DS, Bergstralh EJ, Kramer SA. Prognosis of children with solitary kidney after unilateral nephrectomy. Journal of Urology 1992;148:747‐51. - PubMed
Ariceta 1997 {published data only}
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Arjmandi‐Rafsanjani 2008 {published data only}
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Armstrong 2010 {published data only}
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Arndt 1997 {published data only}
    1. Arndt C, Tefft M, Gehan E, Anderson J, Jenson M, Link M, et al. A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study. Journal of Pediatric Hematology and Oncology 1997;19:124‐9. - PubMed
Arndt 1999 {published data only}
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Arriagada 2009 {published data only}
    1. Arriagada R, Averbeck D, Dahl AA, Darby S, Fossa S, Friberg S, et al. OECI Workshop on late side‐effects of cancer treatments. European Journal of Cancer 2009;45:354‐9. - PubMed
Ashraf 1994 {published data only}
    1. Ashraf MS, Brady J, Breatnach F, Deasy PF, O'Meara A. Ifosfamide nephrotoxicity in paediatric cancer patients. European Journal of Pediatrics 1994;153:90‐4. - PubMed
Ater 2016 {published data only}
    1. Ater JL, Xia C, Mazewski CM, Booth TN, Freyer DR, Packer RJ, et al. Nonrandomized comparison of neurofibromatosis type 1 and non‐neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low‐grade glioma: a report from the Children's Oncology Group. Cancer 2016;122:1928‐36. - PMC - PubMed
Aurer 2016 {published data only}
    1. Aurer I, Nemet D, Mitrović Z, Dujmović D, Bašić‐Kinda S, Radman I, et al. High‐dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma. Annals of Hematology 2016;95:1129‐36. - PubMed
Bacci 2002 {published data only}
    1. Bacci G, Ferrari S, Longhi A, Picci P, Mercuri M, Alvegard TA, et al. High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study. Journal of Chemotherapy 2002;14:198‐206. - PubMed
Bachrach 2014 {published data only}
    1. Bachrach L, Negron E, Liu JS, Su YK, Paparello JJ, Eggener S, et al. Preoperative nuclear renal scan underestimates renal function after radical nephrectomy. Urology 2014;84:1402‐6. - PubMed
Baker 2010 {published data only}
    1. Baker KS, Bresters D, Sande JE. The burden of cure: long‐term side effects following hematopoietic stem cell transplantation (HSCT) in children. Pediatric Clinics of North America 2010;57:323‐42. - PubMed
Barahmani 2009 {published data only}
    1. Barahmani N, Carpentieri S, Li XN, Wang T, Cao Y, Howe L, et al. Glutathione S‐transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma. Neuro‐Oncology 2009;11:292‐300. - PMC - PubMed
Bardi 2004b {published data only}
    1. Bardi E, Bobok I, Olah AV, Olah E, Kappelmayer J, Kiss C. Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatric Nephrology 2004;19:1145‐7. - PubMed
Bardi 2007 {published data only}
    1. Bardi E, Bobok I, Olah V, Kappelmayer J, Kiss C. Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer. Pathology & Oncology Research 2007;13:249‐53. - PubMed
Bashir 2007 {published data only}
    1. Bashir H, Crom D, Metzger M, Mulcahey J, Jones D, Hudson MM. Cisplatin‐induced hypomagnesemia and cardiac dysrhythmia. Pediatric Blood and Cancer 2007;49:867‐9. - PubMed
Baudoin 1993 {published data only}
    1. Baudoin P, Provoost AP, Molenaar JC. Renal function up to 50 years after unilateral nephrectomy in childhood. American Journal of Kidney Disease 1993;21:603‐11. - PubMed
Berg 2006 {published data only}
    1. Berg EE. Osteogenic sarcoma. Orthopaedic Nursing 2006;25:348‐9. - PubMed
Berger 2013 {published data only}
    1. Berger M, Fernandez‐Pineda I, Cabello R, Ramírez‐Villar GL, Márquez‐Vega C, Nustede R. The relationship between the site of metastases and outcome in children with stage IV Wilms tumor: data from 3 European pediatric cancer institutions. Journal of Pediatric Hematology Oncology 2013;35:518‐24. - PubMed
Bergeron 2005 {published data only}
    1. Bergeron C, Dubourg L, Chastagner P, Mechinaud F, Plouvier E, Desfachelles AS, et al. Long‐term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study. Pediatric Blood and Cancer 2005;45:32‐6. - PubMed
Beyzadeoglu 2008 {published data only}
    1. Beyzadeoglu M, Arpaci F, Surenkok S, Ozyigit G, Oysul K, Caglar K, et al. Acute renal toxicity of 2 conditioning regimens in patients undergoing autologous peripheral blood stem‐cell transplantation: total body irradiation‐cyclophosphamide versus ifosfamide, carboplatin, etoposide. Saudi Medical Journal 2008;29:832‐6. - PubMed
Bhatia 2003 {published data only}
    1. Bhatia S. Late effects among survivors of leukemia during childhood and adolescence. Blood Cells, Molecules, and Diseases 2003;31:84‐92. - PubMed
Bhisitkul 1991 {published data only}
    1. Bhisitkul DM, Morgan ER, Vozar MA, Langman CB. Renal functional reserve in long‐term survivors of unilateral Wilms tumor. Journal of Pediatrics 1991;118:698‐702. - PubMed
Bobowski 2016 {published data only}
    1. Bobowski NP, Baker LH. The University of Michigan Sarcoma Survivorship Clinic: preventing, diagnosing, and treating chronic illness for improved survival and long‐term health. Journal of Adolescent and Young Adult Oncology 2016;5:211‐4. - PMC - PubMed
Boddy 1996 {published data only}
    1. Boddy AV, English M, Pearson AD, Idle JR, Skinner R. Ifosfamide nephrotoxicity: limited influence of metabolism and mode of administration during repeated therapy in paediatrics. European Journal of Cancer 1996;32A:1179‐84. - PubMed
Bodei 2008 {published data only}
    1. Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long‐term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y‐DOTATOC and 177Lu‐DOTATATE: the role of associated risk factors. European Journal of Nuclear Medicine and Molecular Imaging 2008;35:1847‐56. - PubMed
Boer 2015 {published data only}
    1. Boer H, Proost JH, Nuver J, Bunskoek S, Gietema JQ, Geubels BM, et al. Long‐term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors. Annals of Oncology 2015;11:2305‐10. - PMC - PubMed
Bolling 2010 {published data only}
    1. Bolling T, Ernst I, Pape H, Martini C, Rube C, Timmermann B, et al. Dose‐volume analysis of radiation nephropathy in children: preliminary report of the RiSK Consortium. International Journal of Radiation Oncology, Biology and Physics 2010;80(3):840‐4. - PubMed
Bonsib 2010 {published data only}
    1. Bonsib SM, Pei Y. The non‐neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important?. Advances in Anatomic Pathology 2010;17:235‐50. - PubMed
Bosl 1988 {published data only}
    1. Bosl GJ, Geller NL, Bajorin D, Leitner SP, Yagoda A, Golbey RB, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good‐prognosis germ cell tumors. Journal of Clinical Oncology 1988;6:1231‐8. - PubMed
Bouillet 2012 {published data only}
    1. Bouillet T. Radiation‐induced nephropathy [Néphropathie post‐radique]. Bulletin du Cancer 2012;99:389‐96. - PubMed
Brade 1991 {published data only}
    1. Brade WP, Herdrich K, Kachel‐Fischer U, Araujo CE. Dosing and side‐effects of ifosfamide plus mesna. Journal of Cancer Research and Clinical Oncology 1991;117 Suppl 4:S164‐86. - PMC - PubMed
Bradley 1998 {published data only}
    1. Bradley J, Reft C, Goldman S, Rubin C, Nachman J, Larson R, et al. High‐energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications. International Journal of Radiation Oncology Biology Physics 1998;40:391‐6. - PubMed
Breslow 2005 {published data only}
    1. Breslow NE, Collins AJ, Ritchey ML, Grigoriev YA, Peterson SM, Green DM. End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. Journal of Urology 2005;174:1972‐5. - PMC - PubMed
Brock 1992 {published data only}
    1. Brock PR, Yeomans EC, Bellman SC, Pritchard J. Cisplatin therapy in infants: short and long‐term morbidity. British Journal of Cancer 1992;Suppl 18:S36‐40. - PMC - PubMed
Bunjes 2002 {published data only}
    1. Bunjes D. 188Re‐labeled anti‐CD66 monoclonal antibody in stem cell transplantation for patients with high‐risk acute myeloid leukemia. Leukemia and Lymphoma 2002;43:2125‐31. - PubMed
Bürger 1985 {published data only}
    1. Bürger D, Moorman‐Voestermans CG, Mildenberger H, Lemerle J, Voute PA, Tournade MF, et al. The advantages of preoperative therapy in Wilms' tumour. A summarised report on clinical trials conducted by the International Society of Paediatric Oncology (SIOP). Zeitschrift für Kinderchirurgie 1985;40:170‐5. - PubMed
Burk 1990 {published data only}
    1. Burk CD, Restaino I, Kaplan BS, Meadows AT. Ifosfamide‐induced renal tubular dysfunction and rickets in children with Wilms tumor. Journal of Pediatrics 1990;117:331‐5. - PubMed
Cachat 1996 {published data only}
    1. Cachat F, Guignard J‐P. Chemotherapy in children and renal side‐effects. Revue Medicale de la Suisse Romande 1996;116:985‐93. - PubMed
Cai 2010 {published data only}
    1. Cai J‐Y, Tang J‐Y, Pan C, Xu M, Xue H‐L, Zhou M, et al. Results of RS‐99 protocol for childhood solid tumors. World Journal of Pediatrics 2010;6:43‐9. - PubMed
Carlson 1993 {published data only}
    1. Carlson K, Smedmyr B, Hagberg H, Oberg G, Simonsson B. Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara‐C, cyclophosphamide) +/‐ TBI and autologous BMT for malignant lymphomas. Bone Marrow Transplantation 1993;11:205‐8. - PubMed
Cassady 1995 {published data only}
    1. Cassady JR. Clinical radiation nephropathy. International Journal of Radiation Oncology Biology Physics 1995;31:1249‐56. - PubMed
Castleberry 1991 {published data only}
    1. Castleberry RP, Kun LE, Shuster JJ, Altshuler G, Smith IE, Nitschke R, et al. Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. Journal of Clinical Oncology 1991;9:789‐95. - PubMed
Chao 2016 {published data only}
    1. Chao C, Xu L, Bell E, Cooper R, Mueller L. Long‐term health outcomes in survivors of childhood cancer diagnosed between 1990 and 2000 in a large US integrated health care system. Journal of Pediatric Hematology/Oncology 2016;38:123‐30. - PubMed
Chen 2007 {published data only}
    1. Chen XF, Zhou FJ, Han H, Qin ZK, Liu ZW, Yu SL, et al. Transabdominal radical nephrectomy for renal cell carcinoma: an experience on 155 patients. Ai.Zheng 2007;26:528‐32. - PubMed
Chen 2016 {published data only}
    1. Chen SH, Hung IJ, Yang CP, Jaing TH, Wang CJ, Hsueh C, et al. Clinical features and long‐term outcomes of bilateral Wilms tumor treated with Taiwan Pediatric Oncology Group protocols: a single center report. Asiac‐Pacific Journal of Clinical Oncology 2016;12:300‐7. - PubMed
Cheng 2008 {published data only}
    1. Cheng JC, Schultheiss TE, Wong JY. Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. International Journal of Radiation Oncology, Biology, Physics 2008;71:1436‐43. - PubMed
Chintagumpala 2015 {published data only}
    1. Chintagumpala M, Eckel SP, Krailo M, Morris M, Adesina A, Packer R, et al. A pilot study using carboplatin, vincristine, and temozolomide in children with progressive/symptomatic low‐grade glioma: a Children's Oncology Group study. Neuro Oncology 2015;17:1132‐8. - PMC - PubMed
Chow 2007 {published data only}
    1. Chow EJ, Pihoker C, Hunt K, Wilkinson K, Friedman DL. Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer 2007;110:2313‐20. - PubMed
Chow 2010 {published data only}
    1. Chow EJ, Simmons JH, Roth CL, Baker KS, Hoffmeister PA, Sanders JE, et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biology of Blood and Marrow Transplantation 2010;16(12):1674‐81. - PMC - PubMed
Chow 2011 {published data only}
    1. Chow EJ, Mueller BA, Baker KS, Cushing‐Haugen KL, Flowers ME, Martin PJ, et al. Cardiovascular hospitalizations and mortality among recipients of hematopoietic stem cell transplantation. Annals of Internal Medicine 2011;155(1):21‐32. - PubMed
Chu 2014 {published data only}
    1. Chu DI, Lloyd JC, Balsara ZR, Wiener JS, Ross SS, Routh JC. Variation in use of nephron‐sparing surgery among children with renal tumors. Journal of Pediatric Urology 2013;10:724‐9. - PMC - PubMed
Coccia 2012 {published data only}
    1. Coccia PF, Altman J, Bhatia S, Borinstein SC, Flynn J, George S, et al. Adolescent and young adult oncology. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network 2012;10:1112‐50. - PubMed
Cohen 1995 {published data only}
    1. Cohen EP, Lawton CA, Moulder JE. Bone marrow transplant nephropathy: radiation nephritis revisited. Nephron 1995;70:217‐22. - PubMed
Cohen 2008 {published data only}
    1. Cohen EP, Irving AA, Drobyski WR, Klein JP, Passweg J, Talano JA, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. International Journal of Radiation Oncology, Biology, Physics 2008;70:1546‐51. - PMC - PubMed
Cohen 2012 {published data only}
    1. Cohen EP, Bedi M, Irving AA, Jacobs E, Tomic R, Klein J, et al. Mitigation of late renal and pulmonary injury after hematopoietic stem cell transplantation. International Journal of Radiation Oncology & Biology & Physics 2012;83:292‐6. - PMC - PubMed
Cole 1994 {published data only}
    1. Cole CH, Pritchard S, Rogers PC, Davis JE, Phillips G, Chan KW. Intensive conditioning regimen for bone marrow transplantation in children with high‐risk haematological malignancies. Medical and Pediatric Oncology 1994;23:464‐9. - PubMed
Conn 1972 {published data only}
    1. Conn JW, Cohen EL, McDonald WJ, Blough WM Jr, Lucas CP, Mayor GH, et al. The syndrome of hypertension, hyperreninemia and secondary aldosteronism associated with renal juxtaglomerular cell tumor (primary reninism). Transactions of the Association of American Physicians 1972;85:353‐68. - PubMed
Cosentino 1993 {published data only}
    1. Cosentino CM, Raffensperger JG, Luck SR, Reynolds M, Sherman JO, Reyes‐Mugica M. A 25‐year experience with renal tumors of childhood. Journal of Pediatric Surgery 1993;28:1350‐4. - PubMed
Cosset 1994 {published data only}
    1. Cosset JM, Socie G, Dubray B, Girinsky T, Fourquet A, Gluckman E. Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations. International Journal of Radiation Oncology, Biology, Physics 1994;30:477‐92. - PubMed
Cost 2012 {published data only}
    1. Cost NG, Adibi M, Lubahn JD, Romman A, Raj GV, Sagalowsky AI, et al. Effect of testicular germ cell tumor therapy on renal function. Urology 2012;80:641‐8. - PubMed
Couto‐Silva 2001 {published data only}
    1. Couto‐Silva AC, Trivin C, Thibaud E, Esperou H, Michon J, Brauner R. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplantation 2001;28:67‐75. - PubMed
Coze 1997 {published data only}
    1. Coze C, Hartmann O, Michon J, Frappaz D, Dusol F, Rubie H, et al. NB87 induction protocol for stage 4 neuroblastoma in children over 1 year of age: a report from the French Society of Pediatric Oncology. Journal of Clinical Oncology 1997;15:3433‐40. - PubMed
Cozzi 1997 {published data only}
    1. Cozzi F, Schiavetti A, Ritchey ML, Green DM, Thomas PRM, Smith GR, et al. Nephron sparing surgery for unilateral Wilms' tumor. Medical and Pediatric Oncology 1997;28:239‐40. - PubMed
Cozzi 2001 {published data only}
    1. Cozzi DA, Schiavetti A, Morini F, Castello MA, Cozzi F. Nephron‐sparing surgery for unilateral primary renal tumor in children. Journal of Pediatric Surgery 2001;36:362‐5. - PubMed
Cozzi 2007 {published data only}
    1. Cozzi F, Zani A, Schiavetti A, Morini F, DeGaetano V, Matrunola M, et al. Compensatory renal growth in children with unilateral renal tumor treated by nephron‐sparing surgery or nephrectomy. European Journal of Pediatric Surgery 2007;17:382‐6. - PubMed
Cozzi 2013a {published data only}
    1. Cozzi DA, Ceccanti S, Frediani S, Mele E, Cozzi F. Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross‐sectional and longitudinal study. Pediatric Blood and Cancer 2013;60:1534‐8. - PubMed
Cozzi 2013b {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. Kidney function following nephrectomy during childhood: response to Timsit et al., Urol Oncol 2012. Urologic Oncology 2013;31:950. - PubMed
Cozzi 2014a {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. RE: Long‐term renal outcome in adolescent and young adult patients nephrectomized for unilateral Wilms tumor. Pediatric Blood and Cancer 2014;61:1715. - PubMed
Cozzi 2014b {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. Glomerular function time trends in long‐term survivors of childhood cancer: a longitudinal study ‐ Letter. Cancer Epidemiology Biomarkers and Prevention 2014;23:675. - PubMed
Cozzi 2015a {published data only}
    1. Cozzi F, Ceccanti S, Cozzi DA. Comment on: Long‐rerm renal function in unilateral non‐syndromic renal tumor survivors treated according to International Society of Pediatric Oncology Protocols. Pediatric Blood and Cancer 2015;62:2249. - PubMed
Cozzi 2015b {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. Comment on: Nephron‐sparing surgery (NSS) for unilateral Wilms tumor (uWT): the SIOP 2001 experience. Pediatric Blood and Cancer 2015;62:1489. - PubMed
Cozzi 2017a {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. Renal function recovery after nephrectomy or nephron sparing surgery in children with unilateral renal tumor. European Journal of Pediatric Surgery 2017;27:74‐80. - PubMed
Cozzi 2017b {published data only}
    1. Cozzi DA, Ceccanti S, Cozzi F. Re: Lopes et al.: "Zero‐Ischemia" Laparoscopic‐assisted partial nephrectomy for the management of selected children with Wilms tumors following neoadjuvant chemotherapy. (Urology 2017;100:103‐110). Urology 2017;100:258‐9. - PubMed
Crist 2001 {published data only}
    1. Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, et al. Intergroup rhabdomyosarcoma study‐IV: results for patients with nonmetastatic disease. Journal of Clinical Oncology 2001;19:3091‐102. - PubMed
Crom 1981 {published data only}
    1. Crom WR, Evans WE, Pratt CB, Senzer N, Denison M, Green AA, et al. Cisplatin disposition in children and adolescents with cancer. Cancer Chemotherapy and Pharmacology 1981;6:95‐9. - PubMed
Culine 1994 {published data only}
    1. Culine S, Lhomme C, Kattan J, Duvillard P, Michel G, Droz J‐P. Long‐term results of two VAB‐like regimens (vinblastine + actinomycin‐D + bleomycin + cyclophosphamide + cisplatin) in malignant germ cell tumours of the ovary. European Journal of Cancer Part A: General Topics 1994;30:1239‐44. - PubMed
Curigliano 2009 {published data only}
    1. Curigliano G, Spitaleri G, Magni E, Lorizzo K, Cobelli O, Locatelli M, et al. Cisplatin, etoposide and continuous infusion bleomycin in patients with testicular germ cell tumors: efficacy and toxicity data from a retrospective study. Journal of Chemotherapy 2009;21:687‐92. - PubMed
D'Angio 1976 {published data only}
    1. D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, et al. The treatment of Wilms' tumor: results of the national Wilms' tumor study. Cancer 1976;38:633‐46. - PubMed
D'Angio 1978 {published data only}
    1. D'Angio GJ, Tefft M, Breslow N, Meyer JA. Radiation therapy of Wilms' tumor: results according to dose, field, post‐operative timing and histology. International Journal of Radiation Oncology, Biology, Physics 1978;4:769‐80. - PubMed
D'Aoust 1979 {published data only}
    1. D'Aoust JC, Prestayko AW, Einhorn LH, Comis RL, Ginsberg SJ, Archambault WA, et al. Cisplatin, bleomycin, and vinblastine combination therapy of testicular tumors: an analysis. Medical and Pediatric Oncology 1979;6:195‐205. - PubMed
Dantonello 2014 {published data only}
    1. Dantonello TM, Lochbühler H, Schuck A, Kube S, Godzinski J, Sköldenberg E, et al. Challenges in the local treatment of large abdominal embryonal rhabdomyosarcoma. Annals of Surgical Oncology 2014;21:3579‐86. - PubMed
Daw 2011 {published data only}
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De Gislain 1990 {published data only}
    1. Gislain C, Dumas M, D'Athis P, Chapuis T, Mayer F, Fargeot P, et al. Plasma creatinine evolution in long term cisplatin therapy. Influence of drug associations. Therapie 1990;45:423‐7. - PubMed
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References to studies awaiting assessment

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Radvansky 2010 {published data only}
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Sierota 2005 {published data only}
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Vanrenterghem 2014 {published data only}
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References to other published versions of this review

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