PDF(Pubmed)
Abstract：
The bidirectional effect of hyperuricemia on chronic kidney disease (CKD) underscores the importance of hyperuricemia as a risk factor for CKD. We evaluated the effect of hyperuricemia on the presence and development of CKD after considering genetic background by calculating polygenic risk scores (PRSs). We employed genome-wide association study summary statistics-excluding the United Kingdom Biobank (UKB) datasets among published CKD Gen Consortium papers-to calculate the PRSs for CKD in white background subjects. To validate PRS performance, we divided the UKB into two datasets to validate and test the data. We used logistic regression analysis to evaluate the association between hyperuricemia and CKD, and performed Kaplan-Meier survival analysis exclusively for subjects with available follow-up data. In total, 438,253 clinical data and 4,307,940 single nucleotide polymorphisms from 459,155 samples were included. We observed a significant positive association between PRS and CKD and the presence and development of CKD. Hyperuricemia significantly increased CKD risk (adjusted odds ratio 1.55, 95% confidence interval 1.48-1.61). The impact of hyperuricemia on CKD was maintained irrespective of PRS range. In addition, negative interaction between hyperuricemia and PRS for CKD was found. Survival analysis indicates that the presence of hyperuricemia significantly increased the risk of CKD development. The PRS for CKD thoroughly reflects the risk of CKD development. Hyperuricemia is a significant indicator of CKD risk, even after incorporating the genetic risk score for CKD. Irrespective of genetic risk, patients with a prospective risk of developing CKD require uric acid monitoring and management.
摘要：
高尿酸血症对慢性肾脏病（CKD）的双向作用强调了高尿酸血症作为CKD危险因素的重要性。在考虑遗传背景后，我们通过计算多基因风险评分（PRS）评估了高尿酸血症对CKD的存在和发展的影响。我们采用全基因组关联研究摘要统计数据-在已发表的CKDGenConsortium论文中不包括英国生物库（UKB）数据集-计算白人背景受试者中CKD的PRS。要验证PRS性能，我们将UKB分成两个数据集来验证和测试数据。我们使用logistic回归分析来评估高尿酸血症与CKD之间的关系。并专门对有随访数据的受试者进行了Kaplan-Meier生存分析。总的来说,包括来自459,155个样品的438,253个临床数据和4,307,940个单核苷酸多态性。我们观察到PRS和CKD与CKD的存在和发展之间存在显著正相关。高尿酸血症显著增加CKD风险（校正比值比1.55，95%置信区间1.48-1.61）。高尿酸血症对CKD的影响与PRS范围无关。此外,发现高尿酸血症与CKD的PRS之间存在负交互作用。生存分析表明，高尿酸血症的存在显着增加了CKD发展的风险。CKD的PRS充分反映了CKD发展的风险。高尿酸血症是CKD风险的重要指标，即使纳入CKD的遗传风险评分。无论遗传风险如何，有发展为CKD的预期风险的患者需要尿酸监测和管理.
