REVEAL-CKD: Prevalence and Consequences of Undiagnosed Chronic Kidney Disease (REVEAL-CKD)

REVEAL-CKD: A Retrospective, Multinational Observational Study to Determine the Prevalence and Consequences of Undiagnosed Chronic Kidney Disease

This is a retrospective, multinational, non-interventional, observational study. A series of cohort studies will be conducted to assess the prevalence of undiagnosed stage 3 CKD in each region. The study will also assess the current state of CKD management in patients with undiagnosed CKD

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease

Detailed Description

This study is a retrospective, multinational, non-interventional observational study. The study does not attempt to test any specific a priori hypothesis; it is descriptive only and will collect data under conditions of routine medical care. Relevant secondary databases will be identified, and a series of cohort studies will be conducted to assess the prevalence of undiagnosed CKD. The study will also assess the current state of CKD management in patients with undiagnosed CKD.

Primary Objectives

1. Estimate the point prevalence of undiagnosed stage 3 CKD (proportion of patients with eGFR measurements indicating stage 3 CKD with no corresponding CKD diagnostic code either before or up to six months after the second abnormal eGFR value)
2. Describe time to CKD diagnosis in patients with no prior CKD diagnosis code at index date (time of second qualifying eGFR), overall and by patient characteristics

Secondary Objectives

1. Assess trends in the prevalence (point prevalence) of undiagnosed CKD by calendar year
2. Describe baseline characteristics among those with undiagnosed versus diagnosed CKD
3. Assess CKD management and monitoring practices (post index date) in patients with diagnosed versus undiagnosed CKD

Exploratory objectives (pending feasibility)

1. Describe the risk of selected adverse clinical outcomes longitudinally among those with undiagnosed versus diagnosed CKD
2. Describe HCRU associated with undiagnosed versus diagnosed CKD
3. Assess association between the timing of the CKD diagnosis and the risk of selected adverse clinical outcomes and HCRU in patients with no CKD diagnosis code prior to the index date
4. Describe health care costs associated with undiagnosed versus diagnosed CKD

5. For CKD patients with eGFR 25-75 mL/min/1.73m2 and urine albumin creatinine ratio (UACR) 200 - 5000 mg/g (DAPA-CKD trial-like population):

   1. Estimate the point prevalence of undiagnosed CKD
   2. Describe the risk of selected adverse clinical outcomes longitudinally among those with undiagnosed CKD
   3. Describe HCRU and costs associated with undiagnosed CKD

• Study Type: Observational
• Enrollment (Actual): 1006361

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2040
      • Research Site
• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Research Site
• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 3G2
      • Research Site
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Research Site
• France
  • Boulogne-Billancourt, France, 92641
    • Research Site
• Germany
  • Frankfurt, Germany, 60549
    • Research Site
• Italy
  • Milan, Italy, 20124
    • Research Site
• Japan
  • Kyoto, Japan, 604-0086
    • Research Site
• Spain
  • Madrid, Spain, 28037
    • Research Site
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, E14 4PU
      • Research Site
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02140
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients ≥18 years old with two consecutive eGFR measurements indicating stage 3 CKD (≥30 and <60 mL/min/1.73m2 using CKD-EPI (preferred) or MDRD equation) recorded more than 90 days apart (max. 730 days), meeting the inclusion criteria will be included in the study (from 2015 onwards).

Description

Inclusion Criteria:

• At least two consecutive eGFR laboratory tests with values ≥30 and <60 mL/min/1.73 m2 (Stage 3A or 3B) that are >90 and ≤730 days apart. The index date is the date of the second eGFR measure meeting the criteria for stage 3 CKD
• At least 12 months of continuous presence in the database or registration in the data prior to the first qualifying eGFR (for data sources with information on enrolment)
• Age ≥18 years at index date

Exclusion Criteria:

• Solid organ transplant before the study index date
• Any evidence of advanced CKD (stage 4, 5) based on CKD diagnostic codes, or renal replacement therapy before the index date

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Stage 3 chronic kidney disease patients; Patients with two consecutive eGFR measurements indicating stage 3 CKD (≥30 and <60 mL/min/1.73m2) during the observation period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of undiagnosed stage 3 chronic kidney disease (CKD)	Undiagnosed stage 3A-3B CKD identified as having no healthcare encounter with a diagnosis code for CKD any time before or up to six months post index date (date of second consecutive estimated glomerular filtration rate [eGFR] value indicating stage 3 CKD recorded at least 90 days after the first abnormal eGFR value), assessed overall and by calendar year	From 2015 assessed throughout the study, up to a maximum of 8 years
Time to CKD diagnosis	Time to CKD diagnosis in patients no CKD diagnosis code any time prior to laboratory measurements indicating stage 3 CKD	From second abnormal eGFR value until the date of CKD diagnosis or end of follow-up, assessed throughout the study period, up to a maximum of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe proportion of patients comorbidities and other patient characteristics	Describe patient characteristics including demographics, clinical assessments, family history, procedures, laboratory measurements, treatment patterns and clinical history (comorbidities) stratified by CKD diagnosis status	From 2015 assessed throughout the study, up to a maximum of 8 years
Proportion of patients monitored for kidney function and complications	Serum Cr test (outpatient); Patients receiving a UACR test (outpatient); Serum calcium; Phosphate; Albumin; Bicarbonate; Potassium; Hemoglobin; Albuminuria	From six months after the second abnormal eGFR measurement, assessed throughout the study period until end of follow-up, up to a maximum 18 months
Proportion of patients tested for CKD	- UACR test	From six months after the second abnormal eGFR measurement, assessed throughout the study period until end of follow-up, up to a maximum 6 months
Proportion of patients prescribed selected medications	Statin prescription; Angiotensin converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs); Sodium-glucose cotransporter-2 (SGLT2) inhibitors; Vaccination (influenza)	From six months after the second abnormal eGFR measurement, assessed throughout the study period until the end of follow-up, up to a maximum 5 years
Proportion of patients monitored for high blood pressure	Patients receiving BP measurement; BP measurement ≤140/90; BP measurement ≤ 130/80 in patients with evidence of albuminuria and/or diabetes	From six months after the second abnormal eGFR measurement, assessed throughout the study period until end of follow-up, up to a maximum 5 years
Proportion of patients monitored for glycaemic control	- HbA1c test in patients with diabetes	From six months after the second abnormal eGFR measurement, assessed throughout the study period until end of follow-up, up to a maximum 5 years
Proportion of patients receiving kidney function monitoring after initiation of angiotensin receptor blocker or angiotensin converting enzyme inhibitors	- An outpatient serum creatinine measurement	From six months after the second abnormal eGFR measurement, assessed throughout the study period until end of follow-up, up to a maximum 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse renal events	Sustained ≥50% reduction in eGFR; or; End stage kidney disease (ESKD); defined as a composite of chronic dialysis, renal transplant, or sustained eGFR<15mL/min/1.732 (at least two consecutive measures ≥28 days apart)	From six months after the second abnormal eGFR until the date of an adverse renal outcome, assessed throughout the study until end of follow-up, up to a maximum of 5 years
Incidence of all-cause mortality	All-cause mortality	From six months after the second abnormal eGFR until death due to any cause, assessed throughout the study until end of follow-up, up to a maximum of 5 years
CKD progression	Progression to CKD stage 4 or higher	From six months after the second abnormal eGFR until the date of CKD progression, assessed throughout the study until end of follow-up, up to a maximum of 5 years
Incidence of Cardiovascular (CV) events	Composite of non-fatal MI, non-fatal stroke, or CV death; Composite of non-fatal MI, non-fatal stroke, or all-cause mortality); Composite of non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or CV death; Stroke; Hospitalisation for heart failure	From six months after the second abnormal eGFR until the date of a CV event, assessed throughout the study until end of follow-up, up to a maximum of 5 years
Describe health care resource utilisation and associated costs	To understand the healthcare resource use and cost associated with undiagnosed CKD	From six months after the second abnormal eGFR, assessed throughout the study until end of follow-up, up to a maximum of 5 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Navdeep Tangri, University of Manitoba

Publications and helpful links

Helpful Links

• The CSR synopsis_D169AR00003

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): November 13, 2023
• Study Completion (Actual): November 13, 2023

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: D169AR00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

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