Effectiveness of Allopurinol on Uric Acid and Pediatric Chronic Kidney Disease Severity in the Chronic Kidney Disease in Children Study

IF 3.2 Q1 UROLOGY & NEPHROLOGY

Kidney Medicine Pub Date : 2025-05-08 DOI:10.1016/j.xkme.2025.101021

Derek K. Ng , Matthew B. Matheson , George J. Schwartz , Katherine E. Kurgansky , Bradley A. Warady , Susan L. Furth , CKiD Study Investigators

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引用次数: 0

Abstract

Rationale & Objective

Clinical trials have shown that serum uric acid reduction does not slow chronic kidney disease (CKD) progression in adults, but it is uncertain whether these findings apply to children.

Study Design

An observational cohort study.

Setting & Population

The Chronic Kidney Disease in Children cohort with participants who initiated allopurinol with a comparison group matched on age, sex, uric acid, CKD diagnosis, estimated glomerular filtration rate (eGFR), and proteinuria.

Exposure

Allopurinol initiation.

Outcomes

Uric acid, eGFR, and proteinuria before and after initiation, and longitudinal changes over time.

Analytical Approach

Allopurinol initiators were matched to noninitiators at a 1:3 ratio. Nonparametric tests compared levels before and after initiation and within-person changes. Linear mixed effects models characterized baseline and longitudinal differences between treatment groups.

Results

A total of 27 participants initiated allopurinol, and these were matched to 81 participants who did not initiate allopurinol. Allopurinol was associated with a 15.9% lower serum uric acid (95% CI, −21.1% to −10.4%) relative to the matched comparison group (P < 0.001) after initiation. There were no significant differences in eGFR or proteinuria over time by group.

Limitations

Observational study designed for comparative effectiveness and relatively small sample size; effectiveness of allopurinol initiated at lower levels of uric acid could not be estimated.

Conclusions

Allopurinol was effective at significantly lowering serum uric acid in children with CKD but was not associated with CKD progression measured by longitudinal eGFR and proteinuria.

Plain-Language Summary

Uric acid is a blood biomarker that is strongly associated with the severity of chronic kidney disease in adults and children. Clinical trials in adults have shown that medications like allopurinol, which reduce uric acid, do not slow progression of kidney disease. This has not been evaluated in children because this disease is rare and trials in this special population are difficult. Using observational data and matching methods in a longitudinal cohort of children with kidney diseases, we evaluated whether allopurinol lowered uric acid and slowed disease progression. Allopurinol significantly and substantially reduced uric acid levels but did not slow in kidney disease progression over about 5 years. These findings were congruent with the hypothesis that higher uric acid is a consequence rather than a cause of kidney disease progression.

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别嘌呤醇在儿童慢性肾病研究中对尿酸和儿童慢性肾病严重程度的影响

基本原理及临床试验表明，血清尿酸降低不能减缓成人慢性肾脏疾病（CKD）的进展，但尚不确定这些发现是否适用于儿童。研究设计：观察性队列研究。设置,在儿童慢性肾脏疾病队列中，开始使用别嘌呤醇的参与者与年龄、性别、尿酸、CKD诊断、估计肾小球滤过率（eGFR）和蛋白尿相匹配的对照组。ExposureAllopurinol起始。结果：起始前后的尿酸、eGFR和蛋白尿，以及随时间的纵向变化。分析方法别嘌呤醇引发剂与非引发剂按1:3的比例匹配。非参数测试比较了初始化前后和人体内变化的水平。线性混合效应模型表征了治疗组之间的基线和纵向差异。结果共有27名参与者开始使用别嘌呤醇，与81名未使用别嘌呤醇的参与者相匹配。与对照组相比，别嘌呤醇与血清尿酸降低15.9%相关（95% CI, - 21.1%至- 10.4%）(P <；0.001)。各组间eGFR和蛋白尿无显著差异。局限性：为比较有效性和相对较小样本量而设计的观察性研究；别嘌呤醇在较低尿酸水平下的有效性无法估计。结论沙罗嘌呤醇可显著降低CKD患儿血清尿酸，但与纵向eGFR和蛋白尿测量的CKD进展无关。尿酸是一种血液生物标志物，与成人和儿童慢性肾脏疾病的严重程度密切相关。成人临床试验表明，别嘌呤醇等降低尿酸的药物并不能减缓肾脏疾病的进展。尚未对儿童进行评估，因为这种疾病很罕见，在这一特殊人群中进行试验很困难。通过对肾病儿童纵向队列的观察数据和匹配方法，我们评估别嘌呤醇是否能降低尿酸并减缓疾病进展。别嘌呤醇显著且实质性地降低了尿酸水平，但在大约5年的时间里没有减缓肾脏疾病的进展。这些发现与高尿酸是肾脏疾病进展的结果而不是原因的假设一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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