Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease

Phase 2

Terminated

Conditions: Chronic Kidney Diseases
Hyperuricemia

Interventions: Drug: Allopurinol

Registration Number: NCT03865407

Lead Sponsor: Virginia Commonwealth University

Brief Summary: Aim 1. To determine the effect of Allopurinol treatment on renal function (glomerular filtration rate, GFR) in pediatric chronic kidney disease (CKD) patients with high uric acid levels (hyperuricemia).

Aim 2. Establish whether Allopurinol treatment reduces Nlrp3 inflammasome and renal injury biomarkers.

Detailed Description: Uric acid levels often rise when kidney function declines. Historically, high uric acid has not been treated unless the uric acid crystallizes in the joint space and causes clinical gout disease, more typically seen in adults. However, new research has shown that high uric acid levels are associated with the development of hypertension, inflammation, and both acute and chronic kidney injury. Adult patients on renal dialysis who have hyperuricemia also have higher mortality rates. In several adult and in one pediatric clinical trial of uric acid lowering therapy (with Allopurinol or Febuxostat), treatment has demonstrated a slower rate of renal function decline and improved blood pressure compared to placebo. The pediatric trial was a 4-month placebo controlled trial of Allopurinol, and showed positive improvement in renal function and blood pressure, but did not adequately control for potential confounders in the outcome. Two known confounders that influence renal function (glomerular filitration rate, GFR) in pediatric CKD are race and glomerular or non-glomerular disease etiology. This study is designed to control for these confounders and establish whether Allopurinol for 6 months of treatment to a goal range of 3-5 mg/dL will improve renal function compared to standard of care. The secondary outcome is to determine whether blood pressure is affected by the treatment and the magnitude of change of serum uric acid. This study will also explore whether Allopurinol treatment alters activation of the Nlrp3 inflammasome or renal injury biomarkers.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Chronic Kidney Disease stage 1-5
Hyperuricemic (UA >= 5.5 mg/dL)

Exclusion Criteria

Contraindication to Allopurinol
Elevated baseline liver function tests
Receiving acute or chronic dialysis
Primary metabolic disorder
Sickle cell disease
Autosomal Dominant Polycystic Kidney Disease
Cystinosis
Bartter or Gitelman Disease
Pregnant or nursing

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allopurinol	Allopurinol	Allopurinol will be administered to this treatment arm group for 6 months. Participants will receive the lowest FDA recommended dose for weight, and will be titrated upwards to achieve the goal uric acid level of 3-5 mg/dL throughout the trial.

Primary Outcome Measures

Name	Time	Method
eGFR Change	The difference in Creatinine eGFR between baseline and 6 months will be measured	Change in Creatinine eGFR over time

Secondary Outcome Measures

Name	Time	Method
Diastolic Blood Pressure	The difference in clinic diastolic blood pressure between baseline and 6 months will be measured	Change in diastolic blood pressure
Serum Uric Acid Change	The difference in Serum Uric Acid between baseline and 6 months will be measured	Change in Serum Uric Acid
Systolic Blood Pressure	The difference in clinic systolic blood pressure between baseline and 6 months will be measured	Change in systolic blood pressure