KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors (CCS) (KINDEST-CCS)

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors (CCS): Prospective Study

Background: Childhood cancer survivors (CCS) are at elevated risk of chronic health conditions. Chemotherapies can cause recurrent acute kidney injury which may progress to kidney fibrosis, chronic kidney disease (CKD) or hypertension (HTN). CCS surviving to adulthood are at ≥3 times the risk (vs. non-CCS) for CKD, HTN and lower quality of life. However, the timing of CKD and HTN onset in CCS completing cancer therapy in childhood remains unclear.

Guidelines provide recommendations on managing post-cancer therapy effects in CCS, but they lack specificity on kidney testing content, frequency and complications. This discord is largely due to knowledge gaps on which CCS develop CKD or HTN after cancer therapy, when outcomes occur and their severity. Existing work has shown in select patients, CKD and HTN in CCS likely begins in the first 5 years post-cancer therapy and that the burden is significant. With robust data on CKD and HTN, international CCS follow-up guidelines can be optimized to include detailed and actionable recommendations on kidney and blood pressure monitoring and treatment.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Chronic Kidney Diseases; Acute Kidney Injury; Nephrotoxicity; Childhood Cancer

Detailed Description

Significant improvements in childhood cancer survival rates have come at the cost of an increase in chronic health conditions. Childhood cancer survivors (CCS) often experience chronic kidney disease (CKD) and hypertension (HTN), yet data on the onset and severity of these diseases in the primary years after childhood cancer therapy is unclear. Both CKD and HTN are major treatable cardiovascular risk factors, and the knowledge gap in the first 5 years after therapy impedes the creation of evidence-based guidelines and early intervention plans.

Currently, the Children's Oncology Group international guidelines, which are used to identify and manage therapy effects in CCS, lack information on CKD testing and appropriate measures. With appropriate treatment, CKD and HTN complications are treatable.

In 500 CCS at high risk for blood pressure (BP) and late kidney effects due to cancer therapy, we will determine the prevalence of HTN and CKD at 3 and 5 years after cancer therapy, and the extent to which eGFR, albuminuria and BP worsen from 3 to 5 years after therapy. In addition, we will assess whether acute kidney injury during cancer therapy and cardiometabolic risk factors are associated with these outcomes.

Based on the evidence from the study, we hope to improve current CCS kidney and BP guidelines to advise on appropriate treatments and measures for HTN and CKD. As CCS are vulnerable to cardiovascular disease, addressing CKD and HTN complications will improve their overall quality of life.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Michael Zappitelli, MD; Phone Number: 304077 4168137605; Email: michael.zappitelli@sickkids.ca
• Study Contact Backup: Name: Yasmine Hejri-Rad, BA; Phone Number: 309031 416-813-7605; Email: yasmine.hejri-rad@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E8
      • Recruiting
      • The Hospital for Sick Children
      • Contact: Yasmine Hejri-Rad, BA; Phone Number: 309031 416-813-7910; Email: yasmine.hejri-rad@sickkids.ca
      • Contact: Salma Abrahim, MSc; Email: salma.abrahim@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Observational cohort study of CCS at 5 Ontario child cancer centres

Description

Inclusion Criteria:

• 3 years ± 6 months after therapy for first cancer
• Received high-risk therapy for first cancer, as defined by the Canadian Oncology Group (COG) as alkylating agents; platinums; abdominal or total body radiation; high dose methotrexate; stem cell transplant; nephrectomy; or other therapy which may be known to possibly cause late kidney and/or BP effects.

Exclusion Criteria:

• Pre-cancer severe CKD and/or previous kidney transplant
• >19 years old at 3 years after cancer therapy completion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Late effects after nephrotoxic chemotherapies.; 3 and 5 year kidney and blood pressure effects after cancer therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Chronic Kidney Disease (CKD) based on eGFR (using an equation) at 3 years post cancer therapy	CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines	3 years +/- 6 months after cancer therapy end
Prevalence of Chronic Kidney Disease (CKD) based on eGFR (using an equation) at 5 years post cancer therapy	CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines	5 years +/- 6 months after cancer therapy end
Prevalence of Hypertension (HTN) from office blood pressure (vis blood pressure machine) at 3 years post cancer therapy	Defined by 2017 American Academy of Pediatrics (AAP) guidelines	3 years +/- 6 months after cancer therapy end
Prevalence of Hypertension (HTN) using Ambulatory Blood Pressure Measurement (ABPM) at 5 years post cancer therapy	The presence of either ambulatory hypertension or masked hypertension	5 years +/- 6 months after cancer therapy end
Change in markers of kidney health (eGFR)(using an equation) between 3 and 5 years post cancer therapy	Change in eGFR in milliliter (mL) /min/1.73m2	Change from 3 to 5 years in eGFR
Change in markers of kidney health (Albuminuria) (using lab values) between 3 and 5 years post cancer therapy	Change in albuminuria in mg/g	Change from 3 to 5 years in Albuminuria
Change in markers of kidney health (Proteinuria) (using Lab values) between 3 and 5 years post cancer therapy	Change in proteinuria in mg/mmol	Change from 3 to 5 years in Proteinuria
Change in markers of cardiovascular health (using blood tests) between 3 and 5 years post cancer therapy	Change in BP percentile as per 2017 American Academy of Pediatrics (AAP) guidelines	Change from 3 to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Acute Kidney Injury (AKI) and Cardiometabolic risk factors (using blood work) at baseline on CKD outcomes	CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines	At baseline for independent factors on CKD outcomes at 3 and 5 years

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Estimated): October 25, 2029
• Study Completion (Estimated): December 31, 2039

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 28, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Acute Kidney Injury
• Other Study ID Numbers: OCREB 4177

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No