A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol
Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this...
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2021
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oai:doaj.org-article:15b7986c609a42cb8982f5a706c42a372021-11-17T23:03:33ZA Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol2054-358110.1177/20543581211057708https://doaj.org/article/15b7986c609a42cb8982f5a706c42a372021-11-01T00:00:00Zhttps://doi.org/10.1177/20543581211057708https://doaj.org/toc/2054-3581Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented. Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults. Design: Observational prospective cohort study. Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both). Patients: Three hundred adults and 300 children planned to receive cisplatin therapy. Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort. Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival. Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge. Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.Anshika JainRyan HuangJasmine LeeNatasha JawaYong Jin LimMike GuronSharon AbishPaul C. BoutrosMichael BrudnoBruce CarletonGeoffrey D. E. CuvelierLakshman GunaratnamCheryl HoKhosrow AdeliSara KuruvillaGiles LajoieGeoffrey LiuPaul C. NathanShahrad Rod RassekhMichael RiederSushrut S. WaikarStephen A. WelchMatthew A. WeirEric WinquistDavid S. WishartAlexandra P. ZorziTom Blydt-HansenMichael ZappitelliBradley UrquhartSAGE PublishingarticleDiseases of the genitourinary system. UrologyRC870-923ENCanadian Journal of Kidney Health and Disease, Vol 8 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Diseases of the genitourinary system. Urology RC870-923 |
| spellingShingle |
Diseases of the genitourinary system. Urology RC870-923 Anshika Jain Ryan Huang Jasmine Lee Natasha Jawa Yong Jin Lim Mike Guron Sharon Abish Paul C. Boutros Michael Brudno Bruce Carleton Geoffrey D. E. Cuvelier Lakshman Gunaratnam Cheryl Ho Khosrow Adeli Sara Kuruvilla Giles Lajoie Geoffrey Liu Paul C. Nathan Shahrad Rod Rassekh Michael Rieder Sushrut S. Waikar Stephen A. Welch Matthew A. Weir Eric Winquist David S. Wishart Alexandra P. Zorzi Tom Blydt-Hansen Michael Zappitelli Bradley Urquhart A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| description |
Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented. Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults. Design: Observational prospective cohort study. Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both). Patients: Three hundred adults and 300 children planned to receive cisplatin therapy. Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort. Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival. Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge. Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices. |
| format |
article |
| author |
Anshika Jain Ryan Huang Jasmine Lee Natasha Jawa Yong Jin Lim Mike Guron Sharon Abish Paul C. Boutros Michael Brudno Bruce Carleton Geoffrey D. E. Cuvelier Lakshman Gunaratnam Cheryl Ho Khosrow Adeli Sara Kuruvilla Giles Lajoie Geoffrey Liu Paul C. Nathan Shahrad Rod Rassekh Michael Rieder Sushrut S. Waikar Stephen A. Welch Matthew A. Weir Eric Winquist David S. Wishart Alexandra P. Zorzi Tom Blydt-Hansen Michael Zappitelli Bradley Urquhart |
| author_facet |
Anshika Jain Ryan Huang Jasmine Lee Natasha Jawa Yong Jin Lim Mike Guron Sharon Abish Paul C. Boutros Michael Brudno Bruce Carleton Geoffrey D. E. Cuvelier Lakshman Gunaratnam Cheryl Ho Khosrow Adeli Sara Kuruvilla Giles Lajoie Geoffrey Liu Paul C. Nathan Shahrad Rod Rassekh Michael Rieder Sushrut S. Waikar Stephen A. Welch Matthew A. Weir Eric Winquist David S. Wishart Alexandra P. Zorzi Tom Blydt-Hansen Michael Zappitelli Bradley Urquhart |
| author_sort |
Anshika Jain |
| title |
A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| title_short |
A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| title_full |
A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| title_fullStr |
A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| title_full_unstemmed |
A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol |
| title_sort |
canadian study of cisplatin metabolomics and nephrotoxicity (accent): a clinical research protocol |
| publisher |
SAGE Publishing |
| publishDate |
2021 |
| url |
https://doaj.org/article/15b7986c609a42cb8982f5a706c42a37 |
| work_keys_str_mv |
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