Preserving Kidney Function in Children With Chronic Kidney Disease

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

Interventions

DIAGNOSTIC_TEST

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.

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.

Sponsors & Collaborators

• Patient-Centered Outcomes Research Institute

  collaborator OTHER

• Children's Hospital Medical Center, Cincinnati

  collaborator OTHER

• Ann & Robert H Lurie Children's Hospital of Chicago

  collaborator OTHER

• Nationwide Children's Hospital

  collaborator OTHER

• Seattle Children's Hospital

  collaborator OTHER

• Stanford University

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• Duke University

  collaborator OTHER

• University of North Carolina, Chapel Hill

  collaborator OTHER

• Indiana University

  collaborator OTHER

• Medical College of Wisconsin

  collaborator OTHER

• University of Iowa

  collaborator OTHER

• Johns Hopkins University

  collaborator OTHER

• University of Michigan

  collaborator OTHER

• University of Florida

  collaborator OTHER

• University of Miami

  collaborator OTHER

• University of Pennsylvania

  collaborator OTHER

• Alfred I. duPont Hospital for Children

  collaborator OTHER

• Children's Hospital of Philadelphia

  lead OTHER

Principal Investigators

• Chris Forrest, MD · Children's Hospital of Philadelphia

• Michelle Denburg, MD · Children's Hospital of Philadelphia

Eligibility

Min Age

1 Year

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-22

Primary Completion

2024-07-31

Completion

2024-07-31

Countries

• United States

Study Locations