Abstract：
OBJECTIVE: The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD.
METHODS: Prospective cohort study.
METHODS: 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.
METHODS: Albuminuria stage at study entry.
RESULTS: Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death.
METHODS: Linear mixed effects and Cox proportional hazards regression analyses.
RESULTS: Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively).
CONCLUSIONS: Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding.
CONCLUSIONS: Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria.
UNASSIGNED: Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.
METHODS: Prospective cohort study.
METHODS: 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.
METHODS: Albuminuria stage at study entry.
RESULTS: Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death.
METHODS: Linear mixed effects and Cox proportional hazards regression analyses.
RESULTS: Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively).
CONCLUSIONS: Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding.
CONCLUSIONS: Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria.
UNASSIGNED: Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.
摘要：
目的：慢性肾脏病（CKD）的临床轨迹，特别是在没有糖尿病的情况下，还没有得到很好的研究。这项研究评估了非糖尿病CKD患者队列中肾脏和心血管预后与蛋白尿水平的关系。
方法：前瞻性队列研究。
方法：1,463名非糖尿病CKD成人，无已知肾小球肾炎，诊断为高血压性肾硬化或CKD原因不明，参与慢性肾功能不全队列（CRIC）研究。
方法：进入研究时的白蛋白尿阶段。
结果：主要结果：复合肾脏（eGFR减半，肾移植,或透析)，次要结果：（1）eGFR斜率，（2）复合心血管疾病事件（心力衰竭住院，心肌梗塞,中风,或全因死亡)，（3）全因死亡。
方法：线性混合效应和Cox比例风险回归分析。
结果：蛋白尿水平较低与女性和年龄较大有关。对于主要结果，与正常白蛋白尿相比，中度和重度白蛋白尿患者的肾脏结局(校正风险比[aHR]3.3,95%CI2.4-4.6;aHR8.6,95%CI6.0-12.0)和心血管结局(aHR1.5,95%CI1.2-1.9;aHR1.5,95%CI1.1-2.0)的发生率较高.那些正常白蛋白尿（<30mcg/mg;N=863）的eGFR下降较慢（-0.46mL/min/1.73m2/年），与中度(30-300微克/毫克，N=372；1.41mL/min/1.73m2/年），或严重的白蛋白尿（>300微克/毫克，N=274；2.63mL/min/1.73m2/年）。肾脏结果，在调整后的分析中，发生,平均而言,与正常白蛋白尿（9.3年）相比，中度（8.6年）和重度（7.3年）白蛋白尿的患者更早，而白蛋白尿组的平均心血管结局时间相似(8.2、8.1和8.6年,分别)。
结论：CKD病因学自我报告，无确证肾活检。残余混杂。
结论：正常白蛋白尿非糖尿病CKD患者的CKD进展明显较慢，但心血管风险低于蛋白尿水平高的患者。这些发现为未来研究的设计提供了信息，该研究旨在调查蛋白尿水平较低的个体的干预措施。
方法：前瞻性队列研究。
方法：1,463名非糖尿病CKD成人，无已知肾小球肾炎，诊断为高血压性肾硬化或CKD原因不明，参与慢性肾功能不全队列（CRIC）研究。
方法：进入研究时的白蛋白尿阶段。
结果：主要结果：复合肾脏（eGFR减半，肾移植,或透析)，次要结果：（1）eGFR斜率，（2）复合心血管疾病事件（心力衰竭住院，心肌梗塞,中风,或全因死亡)，（3）全因死亡。
方法：线性混合效应和Cox比例风险回归分析。
结果：蛋白尿水平较低与女性和年龄较大有关。对于主要结果，与正常白蛋白尿相比，中度和重度白蛋白尿患者的肾脏结局(校正风险比[aHR]3.3,95%CI2.4-4.6;aHR8.6,95%CI6.0-12.0)和心血管结局(aHR1.5,95%CI1.2-1.9;aHR1.5,95%CI1.1-2.0)的发生率较高.那些正常白蛋白尿（<30mcg/mg;N=863）的eGFR下降较慢（-0.46mL/min/1.73m2/年），与中度(30-300微克/毫克，N=372；1.41mL/min/1.73m2/年），或严重的白蛋白尿（>300微克/毫克，N=274；2.63mL/min/1.73m2/年）。肾脏结果，在调整后的分析中，发生,平均而言,与正常白蛋白尿（9.3年）相比，中度（8.6年）和重度（7.3年）白蛋白尿的患者更早，而白蛋白尿组的平均心血管结局时间相似(8.2、8.1和8.6年,分别)。
结论：CKD病因学自我报告，无确证肾活检。残余混杂。
结论：正常白蛋白尿非糖尿病CKD患者的CKD进展明显较慢，但心血管风险低于蛋白尿水平高的患者。这些发现为未来研究的设计提供了信息，该研究旨在调查蛋白尿水平较低的个体的干预措施。
