血清尿酸与常染色体显性遗传性多囊肾病的进展：来自 HALT PKD 试验的结果。
Serum Uric Acid and Progression of Autosomal Dominant Polycystic Kidney Disease: Results from the HALT PKD Trials.
机构信息
University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
出版信息
Curr Hypertens Rev. 2021;17(3):228-237. doi: 10.2174/1573402116666200817113125.
BACKGROUND
Epidemiological studies have suggested that elevated serum uric acid may contribute to the progression of chronic kidney disease. However, no large prospective study has examined whether hyperuricemia is an independent risk factor for the progression of autosomal dominant polycystic kidney disease (ADPKD).
METHODS
We measured uric acid in stored serum samples from the 2-year study visit of 671 participants from the HALT PKD multicenter trials. Participants were categorized according to uric acid tertiles. For Study A (participants aged 15-49 years with preserved kidney function, n=350), we used linear mixed effects models to examine the association between uric acid and repeated measures of height-adjusted total kidney volume (htTKV), the primary outcome for Study A. For Study B (participants aged 18-64 with decreased kidney function, n=321), we used Cox proportional hazards models to assess the hazard for the combined endpoint of 50% loss in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), or death, the primary outcome for Study B. To assess the association of uric acid with the slope of eGFR decline (secondary outcome of HALT A and B), we used linear mixed effects models for the combined population of Study A and B.
RESULTS
In the unadjusted model, the annual change in htTKV was 2.7% higher in the highest uric acid tertile compared to the lowest (p<0.001), but this difference became insignificant after adjustment for gender. Men had faster TKV growth than women (p<0.001). There was no difference in eGFR decline between the 3 uric acid tertiles. Hazard ratios for the clinical endpoint were 2.9 (95% confidence interval, 1.9-4.4) and 1.8 (1.1-2.8) respectively in the high and medium uric acid groups in unadjusted and partially adjusted models (p<0.001), but the significance was lost after adjustment for baseline eGFR. Results were similar when uric acid was examined as a continuous variable.
CONCLUSION
Elevated serum uric acid is not an independent risk factor for disease progression in ADPKD.
背景
流行病学研究表明，血清尿酸升高可能导致慢性肾脏病的进展。然而，尚无大型前瞻性研究探讨高尿酸血症是否是常染色体显性多囊肾病（ADPKD）进展的独立危险因素。
方法
我们检测了 HALT PKD 多中心试验中 671 名参与者在 2 年研究访问时储存的血清样本中的尿酸。根据尿酸三分位数将参与者进行分类。对于研究 A（肾功能正常的 15-49 岁的参与者，n=350），我们使用线性混合效应模型来检验尿酸与身高校正的总肾体积（htTKV）的重复测量值之间的关系，htTKV 是研究 A 的主要结果。对于研究 B（肾功能下降的 18-64 岁的参与者，n=321），我们使用 Cox 比例风险模型评估肾小球滤过率（eGFR）下降 50%、终末期肾病（ESKD）或死亡的联合终点的风险，该终点是研究 B 的主要结果。为了评估尿酸与 eGFR 下降斜率的关系（HALT A 和 B 的次要结果），我们使用线性混合效应模型对研究 A 和 B 的合并人群进行分析。
结果
在未调整模型中，与最低尿酸三分位相比，最高尿酸三分位的 htTKV 年变化率高 2.7%（p<0.001），但在校正性别后差异变得不显著。男性的 TKV 增长速度快于女性（p<0.001）。在 3 个尿酸三分位之间，eGFR 下降率没有差异。在未调整和部分调整模型中，高尿酸组和中尿酸组的临床终点风险比分别为 2.9（95%置信区间，1.9-4.4）和 1.8（1.1-2.8）（p<0.001），但在校正基线 eGFR 后，显著性丧失。当尿酸被视为连续变量时，结果相似。
结论
血清尿酸升高不是 ADPKD 疾病进展的独立危险因素。
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