Empagliflozin lowers serum uric acid in chronic kidney disease: exploratory analyses from the EMPA-KIDNEY trial.

IF 4.8 2区医学 Q1 TRANSPLANTATION

Nephrology Dialysis Transplantation Pub Date : 2024-09-14 DOI:10.1093/ndt/gfae203

Kaitlin J Mayne,Rebecca J Sardell,Natalie Staplin,Parminder K Judge,Doreen Zhu,Emily Sammons,David Z I Cherney,Jennifer B Green,Adeera Levin,Roberto Pontremoli,Sibylle J Hauske,Jonathan Emberson,David Preiss,Martin J Landray,Colin Baigent,Christoph Wanner,Richard Haynes,William G Herrington,

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Abstract

BACKGROUND AND HYPOTHESIS Hyperuricaemia and gout are common in chronic kidney disease (CKD). We aimed to assess the effects of sodium-glucose co-transporter-2 (SGLT2) inhibition on uric acid (urate) and gout in patients with CKD. METHODS The EMPA-KIDNEY trial randomised 6609 patients with CKD (estimated glomerular filtration rate [eGFR] ≥20 and <90 mL/min/1.73m2) to receive either empagliflozin 10 mg daily or matching placebo over a median of two years follow-up. Serum uric acid was measured at randomisation then 2 and 18 months of follow-up and the effects of empagliflozin were analysed using a pre-specified mixed model repeated measures approach. Participant-reported gout events were analysed in Cox regression models (first events) with the Andersen-Gill extension (total events). A post-hoc composite outcome included new initiation of uric acid lowering therapy or colchicine. EMPA-KIDNEY primary and kidney disease progression outcomes were also assessed in subgroups of baseline serum uric acid. RESULTS Baseline mean ± SD serum uric acid concentration was 431±114 µmol/L. Allocation to empagliflozin resulted in a study-average between-group difference in serum uric acid of -25.6 (95%CI -30.3,-21.0) µmol/L with larger effects in those with higher eGFR (trend P < 0.001) and without diabetes (heterogeneity P < 0.001). Compared to placebo, empagliflozin did not significantly reduce first or total gout events (HR 0.87, 95%CI 0.74-1.02 for the 595 first events, and 0.86, 0.72-1.03 for the 869 total events) with similar hazard ratios for the post-hoc composite and across subgroups, including by diabetes and eGFR. The effect of empagliflozin on the primary outcome and kidney disease progression outcomes were similar irrespective of baseline level of uric acid. CONCLUSION SGLT2 inhibition reduces serum uric acid in patients with CKD with larger effects at higher eGFR and in the absence of diabetes. However, the effect on uric acid is modest and did not translate into reduced risk of gout in EMPA-KIDNEY.

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恩格列净降低慢性肾病患者的血清尿酸：EMPA-KIDNEY 试验的探索性分析。

背景和假设尿酸血症和痛风在慢性肾脏病（CKD）中很常见。方法EMPA-KIDNEY试验随机抽取了6609名CKD患者（估计肾小球滤过率[eGFR]≥20且<90 mL/min/1.73m2），让他们在中位两年的随访期间接受每天10 mg的empagliflozin或相同的安慰剂。在随机分组、2个月和18个月随访期间测量血清尿酸，并采用预先指定的混合模型重复测量方法分析empagliflozin的效果。参与者报告的痛风事件通过Cox回归模型（首次事件）和Andersen-Gill扩展模型（总事件）进行分析。事后综合结果包括新开始的降尿酸治疗或秋水仙碱治疗。还对基线血清尿酸亚组的 EMPA-KIDNEY 初治和肾病进展结果进行了评估。结果基线平均±标清尿酸浓度为 431±114 µmol/L。分配到empagliflozin后，研究组间平均血清尿酸差异为-25.6 (95%CI -30.3,-21.0) µmol/L，对eGFR较高者（趋势P < 0.001）和无糖尿病者（异质性P < 0.001）的影响更大。与安慰剂相比，empagliflozin并不能显著减少首次痛风事件或总痛风事件（595例首次痛风事件的HR为0.87，95%CI为0.74-1.02；869例总痛风事件的HR为0.86，0.72-1.03）。无论基线尿酸水平如何，empagliflozin对主要结局和肾脏疾病进展结局的影响相似。然而，在 EMPA-KIDNEY 项目中，对尿酸的影响不大，也没有转化为痛风风险的降低。

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来源期刊

Nephrology Dialysis Transplantation 医学-泌尿学与肾脏学

CiteScore

10.10

自引率

4.90%

发文量

1431

审稿时长

1.7 months

期刊介绍： Nephrology Dialysis Transplantation (ndt) is the leading nephrology journal in Europe and renowned worldwide, devoted to original clinical and laboratory research in nephrology, dialysis and transplantation. ndt is an official journal of the [ERA-EDTA](http://www.era-edta.org/) (European Renal Association-European Dialysis and Transplant Association). Published monthly, the journal provides an essential resource for researchers and clinicians throughout the world. All research articles in this journal have undergone peer review. Print ISSN: 0931-0509.