Rachel Shulman, Wei Yang, Debbie L Cohen, Peter P Reese, Jordana B Cohen
{"title":"Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study.","authors":"Rachel Shulman, Wei Yang, Debbie L Cohen, Peter P Reese, Jordana B Cohen","doi":"10.1053/j.ajkd.2024.05.008","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale & objective: </strong>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.</p><p><strong>Study design: </strong>Prospective cohort study.</p><p><strong>Setting & participants: </strong>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.</p><p><strong>Exposure: </strong>Albuminuria stage at study entry.</p><p><strong>Outcome: </strong>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.</p><p><strong>Analytical approach: </strong>Linear mixed effects and Cox proportional hazards regression analyses.</p><p><strong>Results: </strong>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/1.73m<sup>2</sup> per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m<sup>2</sup> per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m<sup>2</sup> 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).</p><p><strong>Limitations: </strong>Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Plain-language summary: </strong>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.</p>","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Kidney Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1053/j.ajkd.2024.05.008","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale & 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.
Study design: Prospective cohort study.
Setting & participants: 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.
Exposure: Albuminuria stage at study entry.
Outcome: 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.
Analytical approach: 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).
Limitations: 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.
Plain-language summary: 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.
理由和目标:对于正常白蛋白尿型慢性肾脏病(CKD)的临床轨迹,尤其是在无糖尿病的情况下,尚未进行深入研究。本研究评估了非糖尿病慢性肾脏病患者队列中肾脏和心血管预后与白蛋白尿水平的关系:前瞻性队列研究:参加慢性肾功能不全队列(CRIC)研究的1,463名非糖尿病慢性肾功能不全成人患者,无已知肾小球肾炎,被诊断为高血压肾硬化症或慢性肾功能不全原因不明:研究开始时的白蛋白尿分期:主要结果次要结局:(1) eGFR斜率;(2) 复合心血管疾病事件(因心力衰竭、心肌梗死、中风或全因死亡住院);(3) 全因死亡:分析方法:线性混合效应和考克斯比例危险回归分析:结果:白蛋白尿水平较低与女性和年龄较大有关。就主要结果而言,与正常白蛋白尿相比,中度和重度白蛋白尿患者的肾脏结果(调整后危险比[aHR]3.3,95% CI 2.4-4.6;aHR 8.6,95% CI 6.0-12.0)和心血管结果(aHR 1.5,95% CI 1.2-1.9;aHR 1.5,95% CI 1.1-2.0)发生率较高。正常白蛋白尿患者(300 毫克/毫克,N=274;2.63 毫升/分钟/1.73 平方米/年)。在调整分析中,与正常白蛋白尿患者(9.3年)相比,中度(8.6年)和重度(7.3年)白蛋白尿患者出现肾脏疾病结果的平均时间更早,而各组白蛋白尿患者出现心血管疾病结果的平均时间相似(分别为8.2年、8.1年和8.6年):局限性:CKD病因自我报告,未进行肾活检确诊。结论:正常白蛋白尿型非糖尿病慢性肾脏病患者的慢性肾脏病进展速度大大减缓,但心血管风险仅略低于白蛋白尿水平高的患者。这些发现为今后设计针对白蛋白尿水平较低人群的干预研究提供了参考。
期刊介绍:
The American Journal of Kidney Diseases (AJKD), the National Kidney Foundation's official journal, is globally recognized for its leadership in clinical nephrology content. Monthly, AJKD publishes original investigations on kidney diseases, hypertension, dialysis therapies, and kidney transplantation. Rigorous peer-review, statistical scrutiny, and a structured format characterize the publication process. Each issue includes case reports unveiling new diseases and potential therapeutic strategies.