Singapore Eye Research Institute, Singapore National Eye Centre, 20 College Road, The Academia, Level 6, Singapore, 169856, Singapore.
Eye-ACP, Duke-NUS Medical School, Singapore, Singapore.
J Nephrol. 2024 May;37(4):1007-1016. doi: 10.1007/s40620-023-01872-w. Epub 2024 Feb 3.
The prevalence of chronic kidney disease (CKD) is high. Identification of cases with CKD or at high risk of developing it is important to tailor early interventions. The objective of this study was to identify blood metabolites associated with prevalent and incident severe CKD, and to quantify the corresponding improvement in CKD detection and prediction.
Data from four cohorts were analyzed: Singapore Epidemiology of Eye Diseases (SEED) (n = 8802), Copenhagen Chronic Kidney Disease (CPH) (n = 916), Singapore Diabetic Nephropathy (n = 714), and UK Biobank (UKBB) (n = 103,051). Prevalent CKD (stages 3-5) was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m; incident severe CKD as CKD-related mortality or kidney failure occurring within 10 years. We used multivariable regressions to identify, among 146 blood metabolites, those associated with CKD, and quantify the corresponding increase in performance.
Chronic kidney disease prevalence (stages 3-5) and severe incidence were 11.4% and 2.2% in SEED, and 2.3% and 0.2% in UKBB. Firstly, phenylalanine (Odds Ratio [OR] = 1.83 [1.73, 1.93]), tyrosine (OR = 0.75 [0.71, 0.79]), docosahexaenoic acid (OR = 0.90 [0.85, 0.95]), citrate (OR = 1.41 [1.34, 1.47]) and triglycerides in medium high density lipoprotein (OR = 1.07 [1.02, 1.13]) were associated with prevalent stages 3-5 CKD. Mendelian randomization analyses suggested causal relationships. Adding these metabolites beyond traditional risk factors increased the area under the curve (AUC) by 3% and the sensitivity by 7%. Secondly, lactate (HR = 1.33 [1.08, 1.64]) and tyrosine (HR = 0.74 [0.58, 0.95]) were associated with incident severe CKD among individuals with eGFR < 90 mL/min/1.73 m at baseline. These metabolites increased the c-index by 2% and sensitivity by 5% when added to traditional risk factors.
The performance improvements of CKD detection and prediction achieved by adding metabolites to traditional risk factors are modest and further research is necessary to fully understand the clinical implications of these findings.
慢性肾脏病（CKD）的患病率很高。识别患有 CKD 或有发展为 CKD 风险的病例对于进行早期干预很重要。本研究的目的是确定与普遍存在和新发性严重 CKD 相关的血液代谢物，并量化其对 CKD 检测和预测的相应改善。
对四个队列的数据进行了分析：新加坡眼病流行病学研究（SEED）（n=8802）、哥本哈根慢性肾脏病（CPH）（n=916）、新加坡糖尿病肾病（n=714）和英国生物银行（UKBB）（n=103051）。CKD 的患病率（3-5 期）定义为估算肾小球滤过率（eGFR）<60 mL/min/1.73 m2；新发性严重 CKD 定义为 CKD 相关死亡率或肾功能衰竭在 10 年内发生。我们使用多变量回归来确定 146 种血液代谢物中与 CKD 相关的代谢物，并量化其对性能的相应提高。
SEED 中 CKD 的患病率（3-5 期）和严重发生率分别为 11.4%和 2.2%，UKBB 中分别为 2.3%和 0.2%。首先，苯丙氨酸（比值比 [OR] 1.83 [1.73, 1.93]）、酪氨酸（OR 0.75 [0.71, 0.79]）、二十二碳六烯酸（OR 0.90 [0.85, 0.95]）、柠檬酸（OR 1.41 [1.34, 1.47]）和中高密度脂蛋白中的甘油三酯（OR 1.07 [1.02, 1.13]）与普遍存在的 CKD 3-5 期相关。孟德尔随机化分析表明存在因果关系。在传统危险因素之外添加这些代谢物可使曲线下面积（AUC）增加 3%，敏感性增加 7%。其次，在基线时 eGFR<90 mL/min/1.73 m2 的个体中，乳酸（HR 1.33 [1.08, 1.64]）和酪氨酸（HR 0.74 [0.58, 0.95]）与新发性严重 CKD 相关。当将这些代谢物添加到传统危险因素中时，c 指数增加 2%，敏感性增加 5%。
将代谢物添加到传统危险因素中对 CKD 检测和预测的性能提高是适度的，需要进一步研究以充分了解这些发现的临床意义。
