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

Recruiting
Conditions
Nephrotoxicity
Acute Kidney Injury
Chronic Kidney Diseases
Hypertension
Childhood Cancer
Registration Number
NCT06153147
Lead Sponsor
The Hospital for Sick Children
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
500
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Prevalence of Hypertension (HTN) from office blood pressure (vis blood pressure machine) at 3 years post cancer therapy3 years +/- 6 months after cancer therapy end

Defined by 2017 American Academy of Pediatrics (AAP) guidelines

Prevalence of Chronic Kidney Disease (CKD) based on eGFR (using an equation) at 3 years post cancer therapy3 years +/- 6 months after cancer therapy end

CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines

Prevalence of Chronic Kidney Disease (CKD) based on eGFR (using an equation) at 5 years post cancer therapy5 years +/- 6 months after cancer therapy end

CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines

Change in markers of kidney health (Albuminuria) (using lab values) between 3 and 5 years post cancer therapyChange from 3 to 5 years in Albuminuria

Change in albuminuria in mg/g

Change in markers of kidney health (Proteinuria) (using Lab values) between 3 and 5 years post cancer therapyChange from 3 to 5 years in Proteinuria

Change in proteinuria in mg/mmol

Prevalence of Hypertension (HTN) using Ambulatory Blood Pressure Measurement (ABPM) at 5 years post cancer therapy5 years +/- 6 months after cancer therapy end

The presence of either ambulatory hypertension or masked hypertension

Change in markers of kidney health (eGFR)(using an equation) between 3 and 5 years post cancer therapyChange from 3 to 5 years in eGFR

Change in eGFR in milliliter (mL) /min/1.73m2

Change in markers of cardiovascular health (using blood tests) between 3 and 5 years post cancer therapyChange from 3 to 5 years

Change in BP percentile as per 2017 American Academy of Pediatrics (AAP) guidelines

Secondary Outcome Measures
NameTimeMethod
Impact of Acute Kidney Injury (AKI) and Cardiometabolic risk factors (using blood work) at baseline on CKD outcomesAt baseline for independent factors on CKD outcomes at 3 and 5 years

CKD: Per Kidney Disease Improving Global Outcomes (KDIGO) guidelines

Trial Locations

Locations (1)

The Hospital For Sick Children

🇨🇦

Toronto, Ontario, Canada

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