RATIONALE & OBJECTIVE Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function. STUDY DESIGN Genome-wide association study (GWAS) and Mendelian randomization. SETTING & PARTICIPANTS UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries. EXPOSURE Coffee consumption. OUTCOMES Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m2), and albuminuria. ANALYTICAL APPROACH GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen. RESULTS 2,126 SNPs were associated with coffee consumption (P<5×10-8), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (β=0.022; P=1.6×10-6) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10-15). LIMITATIONS Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations. CONCLUSIONS This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.

中文翻译：

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咖啡消耗和肾脏功能：孟德尔随机研究。

理由和目标慢性肾脏病（CKD）是全球发病率和死亡率的主要原因，其预防和治疗策略有限。咖啡是化学物质的复杂混合物，消费与大多数有益于健康的结果有关。这项工作旨在确定咖啡摄入量对肾功能的影响。研究设计全基因组关联研究（GWAS）和孟德尔随机化。地点和参与者英国生物库基线数据用于咖啡消费量GWAS，包括227,666名参与者。CKDGen联合会的数据用于肾脏结局分析，包括来自不同国家的133814名参与者（大部分为CKD病例，共12385例），主要来自欧洲血统。暴露咖啡消耗量。结果肾小球滤过率（eGFR），CKD GFR类别3至5（G3-G5; eGFR <60mL / min / 1.73m2）和蛋白尿。GWAS的分析方法可识别UK Biobank中与咖啡消耗量相关的单核苷酸多态性（SNP），并在CKDGen中对咖啡消耗量和肾脏结局的孟德尔随机分析中使用这些SNP。结果2,126个SNP与咖啡消耗量相关（P <5×10-8），其中25个是独立的，可在CKDGen中获得。每天多喝一杯咖啡对CKD G3-G5（OR，0.84; 95％CI，0.72-0.98; P = 0.03）和白蛋白尿（OR，0.81; 95％CI，0.67-0.97; P = 0.02）。在去除负责显着异质性的3个SNPs后，额外的杯子也与更高的eGFR（β= 0.022; P = 1.6×10-6）相关（Cochran QP = 3.5×10-15）。局限性用来测定肌酐和白蛋白的试验因提供数据的研究而异，并且针对蛋白尿使用的是针对性别的定义，而不是KDIGO指南建议。结论本研究提供了咖啡对肾脏功能有益作用的证据。鉴于咖啡的广泛消费以及防止CKD发生和发展的干预措施有限，鉴于全球CKD负担日益增加，这可能对全球公共卫生产生重大影响。