Preserving Kidney Function in Children With Chronic Kidney Disease

NCT ID: NCT05169411

Last Updated: 2024-08-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20240 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-22
• Study Completion Date: 2024-07-31

Brief Summary

Pediatric chronic kidney disease (CKD) results from health conditions that reduce kidney function for >3 months. It can progress to end-stage kidney disease (ESKD), which requires dialysis or kidney transplant. In adults, CKD is common and caused mainly by hypertension and diabetes. CKD in childhood is rare and caused primarily by congenital anomalies of the genitourinary system and immune-mediated disorders. The best estimate of pediatric CKD prevalence is <1/15,000 pediatric population. Hypertension occurs in 50% of affected children and is a major risk factor for decline in kidney function. Several clinical practice guidelines have offered recommendations for blood pressure (BP) management in pediatric CKD; however, clinical trial and large-scale observational data are limited, leading to a weak evidence base and substantial practice variation. The purpose of PRESERVE is to provide new knowledge to inform shared decision-making regarding BP management for pediatric CKD. We will leverage the Patient-Centered Outcomes Research network (PCORnet®) infrastructure to conduct large-scale observational studies that will address BP management knowledge gaps for pediatric CKD and sub-groups for whom antihypertensive treatment and outcome associations may be different (e.g., cause of kidney disease and proteinuria).

The project's specific aims are:

Aim 1-Enhance the PCORnet Common Data Model (CDM) for pediatric and rare kidney disease research. We will expand and improve the PCORnet CDM with new pediatric- and kidney-specific variables, study-specific data quality optimization, and linkage with the chronic kidney disease in children (CKiD) cohort study and the US Renal Data System (USRDS). CKiD directly measures kidney function [ie, glomerular filtration rate (GFR)] and includes Ambulatory Blood Pressure Monitoring (ABPM). The USRDS provides complete capture of renal replacement therapy [(RRT) dialysis and transplant], two components of the primary clinical outcome.

Aim 2-Describe and examine the effectiveness of consistent BP and urine protein monitoring for preserving kidney function. We will describe the consistency of BP and urine protein monitoring and will contrast clinic BP assessments with ABPM. In longitudinal analyses, we will evaluate the effects of consistent monitoring of BP and urine protein on kidney function decline.

Aim 3-Compare the effectiveness of BP medication strategies for preserving kidney function. We will compare the effects of (1) BP levels when treatment was started, (2) choice of first-line therapies, and (3) ongoing BP control on kidney function decline. We will also assess adverse events related to hypertension management.

Aim 4-Assess patients' lived experiences related to BP management. We will field a survey that examines patient-centered outcomes by level of BP control and medication management approaches. This Aim will provide information on experiences with BP management from the perspectives of patients, parents, and clinicians that will complement the clinical outcomes studied in Aims 2 and 3.

Conditions

Chronic Kidney Disease Stage 2; Chronic Kidney Disease Stage 3; Pediatric Kidney Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) categories

The first anti-hypertensive prescribed will be categorized as ACEi, ARB, thiazide diuretic, loop diuretic, beta-blocker, calcium channel blocker, other, and none.

Blood pressure

Intervention Type: DIAGNOSTIC_TEST

The first anti-hypertensive prescribed will be categorized as ACEi, ARB, thiazide diuretic, loop diuretic, beta-blocker, calcium channel blocker, other, and none; secondary analyses will combine ACEi and ARB into a single RAAS blocker category. We will conduct additional secondary analyses for specific medications with sufficient sample sizes.

Combined renin-angiotensin-aldosterone system (RAAS) blocker category

Secondary analyses will combine ACEi and ARB into a single RAAS blocker category.

Blood pressure

Intervention Type: DIAGNOSTIC_TEST

The first anti-hypertensive prescribed will be categorized as ACEi, ARB, thiazide diuretic, loop diuretic, beta-blocker, calcium channel blocker, other, and none; secondary analyses will combine ACEi and ARB into a single RAAS blocker category. We will conduct additional secondary analyses for specific medications with sufficient sample sizes.

Urine protein dichotomous indicator

We will determine whether urine protein is evaluated at each encounter and create a dichotomous indicator.

Urine protein

Intervention Type: DIAGNOSTIC_TEST

Evaluating urine protein for children with CKD and hypertension is another guideline recommendation, but the frequency, type of assessment (qualitative or quantitative urine protein), and utility for patients without hypertension are unclear. We will determine whether urine protein is evaluated at each encounter and create a dichotomous indicator.

Interventions

Blood pressure

The first anti-hypertensive prescribed will be categorized as ACEi, ARB, thiazide diuretic, loop diuretic, beta-blocker, calcium channel blocker, other, and none; secondary analyses will combine ACEi and ARB into a single RAAS blocker category. We will conduct additional secondary analyses for specific medications with sufficient sample sizes.

Intervention Type: DIAGNOSTIC_TEST

Urine protein

Evaluating urine protein for children with CKD and hypertension is another guideline recommendation, but the frequency, type of assessment (qualitative or quantitative urine protein), and utility for patients without hypertension are unclear. We will determine whether urine protein is evaluated at each encounter and create a dichotomous indicator.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Include: patient has an outpatient, ED, or inpatient visit with a physician
• Include: 1 or more eGFR values 30-89 mL/min/1.73m2 using the CKiD U25 formula
• Include: 2 or more eGFR values 30-89 mL/min/1.73m2 on different days using the CKiD U25 formula
• Include: 2 eGFR values in the range 30-89 mL/min/1.73m2 using the CKiD U25 formula greater than or equal to 90 days apart.

Exclusion Criteria

• Exclude: eGFR value >=90 ml/min using the CKiD U25 formula between the two qualifying eGFRs in mild-moderate range
• Exclude if: Age <1 and >=18 years on CED (see below for definition of CED)
• Exclude if: no nephrologist visit at any time during the study period
• Exclude: if chronic dialysis on or before CED
• Exclude: if kidney transplant on or before CED

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Alfred I. duPont Hospital for Children

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Forrest, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Michelle Denburg, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

RD-2020C22-0338

Identifier Type: OTHER

Identifier Source: secondary_id

21-018814

Identifier Type: -

Identifier Source: org_study_id