近端小管清除蛋白质结合的溶质是一种固有的肾脏机制,用于去除可能对人体产生心血管毒性的假定尿毒症毒素。然而,慢性肾脏病(CKD)患者肾脏分泌溶质清除率受损与心血管事件之间的潜在关联仍不确定.
多中心,prospective,队列研究。
我们评估了来自慢性肾功能不全队列(CRIC)研究的3,407名参与者。
8种分泌溶质的基线肾清除率。我们使用液相色谱-串联质谱法(LC-MS/MS)测量了血浆和配对24小时尿液样本中分泌溶质的浓度。
突发心力衰竭,心肌梗塞,和中风事件。
我们使用Cox回归来评估基线分泌溶质清除率与根据估计的GFR(eGFR)和其他混杂因素调整的事件研究结果的相关性。
参与者的平均年龄为56岁;45%为女性;41%为黑人;估计肾小球滤过率(eGFR)的中位数为43mL/min/1.73m2。在控制人口统计学和传统危险因素后的长期随访中,分泌溶质的24小时肾脏清除率较低与心力衰竭和心肌梗死有关,但与卒中无关。然而,校正eGFR后,这些相关性减弱,无统计学意义.
排除基线时eGFR严重降低的患者;分泌溶质清除率的测量变异性。
在一项全国CKD队列研究中,在内源性分泌溶质的肾脏清除率与心力衰竭之间未观察到临床或统计学相关的关联。心肌梗塞,或调整eGFR后的行程。这些发现表明,在轻度至中度CKD患者中,除了肾小球GFR和蛋白尿的测量外,肾小管分泌清除几乎没有提供有关心血管疾病事件发展的其他信息。
The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.
A multicenter, prospective, cohort
study.
We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC)
study.
Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Incident heart failure, myocardial infarction, and stroke events.
We used Cox regression to evaluate associations of baseline secretory solute clearances with incident
study outcomes adjusting for estimated GFR (eGFR) and other confounders.
Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR.
Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances.
In a national cohort
study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.