Long-term metabolic effects of kidney events with intensive SBP control

强化收缩压控制对肾脏事件的长期代谢影响

• 批准号: 10223281
• 负责人: SRINIVASAN BEDDHU
• 金额: $ 27.75万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223281
• 关键词: Acute; Address; Adverse effects; Biological; Blood Pressure; Bone Diseases; C-reactive protein; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical; Data; Diabetes Mellitus; Disease; End stage renal failure; Event; Glomerular Filtration Rate; Glycosylated Hemoglobin; Goals; Heart failure; Hypertension; Incidence; Inflammation; Intervention Trial; Kidney; Kidney Diseases; Knowledge; Level of Evidence; Long-Term Effects; Mediating; Mediation; Metabolic; Metabolic Marker; Metabolism; MicroRNAs; Minerals; Modernization; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Outcome; PTH gene; Participant; Patients; Persons; Public Health; Publications; Renal function; Risk; Role; Serum; Specimen; Stroke; Sudden Death; Techniques; Testing; Vascular calcification; alpha-Fetoproteins; blood pressure intervention; blood pressure regulation; bone; cardiovascular effects; cardiovascular risk factor; causal model; clinically relevant; design; epidemiology study; fibroblast growth factor 23; follow-up; glycemic control; hazard; hepcidin; inflammatory marker; iron metabolism; mortality; mortality risk; novel; primary endpoint; public health relevance; secondary endpoint

The Systolic Blood Pressure Intervention Trial (SPRINT), a landmark study demonstrated that intensive systolic blood pressure (SBP) lowering (SBP target <120 versus <140 mmHg) reduced the risk of death and major cardiovascular events in persons without diabetes but at high cardiovascular risk. In a recent publication, we noted that intensive SBP lowering in SPRINT resulted in a relative mean decline in estimated glomerular filtration rate (eGFR) (intensive versus standard) of −3.31 ± 0.30 mL/min/1.73 m2 by 6 months. The intensive SBP group also had a 3.5-fold higher hazard of incident chronic kidney disease (CKD). The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial used a 2 X 2 factorial design to test the same SBP intervention as SPRINT as well as intensive versus standard glycemic control (glycated hemoglobin < 6% versus 7.0 to 7.8%) in persons with type 2 diabetes mellitus (T2DM). In our analysis of ACCORD-BP data, comparisons of the intensive vs. standard SBP groups showed that the intensive SBP intervention in ACCORD-BP led to an even more pronounced early mean eGFR decline and a greater increase in the cumulative incidence of CKD relative to SPRINT (interaction p-value <0.001). It is possible that the decline in eGFR due to blood pressure lowering may have distinct clinical and public health consequences compared with the decline in eGFR due to other conditions, which we have presumed to be related to progression of intrinsic kidney disease. As the follow-up periods are too short to determine the long-term effects of acute, early eGFR decline/incident CKD on hard endpoints, stored specimens from both studies provide an opportunity to study parallel effects on metabolic markers reflecting key outcome domains of inflammation/ iron metabolism and bone and mineral metabolism/ vascular calcification. Herein we propose to examine the long-term metabolic implications of acute, early eGFR decline/incident CKD in SPRINT and ACCORD-BP. The analyses of Aim 1 will address consequences of acute changes in eGFR and incident CKD that are due to the SBP interventions as well as consequences of changes in GFR due to other factors including the natural course of kidney disease. Aim 2 will use modern causal modeling techniques to address the consequences of acute changes in eGFR and incident CKD that are specifically due to the intensive SBP intervention. The current proposal will clarify whether changes in eGFR and incident CKD noted with intensive SBP lowering result in an altered metabolic milieu. Prior to SPRINT, there was no RCT level evidence that intensive SBP control to a goal of <120 mm Hg prolongs survival and reduces the risk of cardiovascular events. While SPRINT findings are novel and significant, there are concerns about the kidney effects of the SPRINT intervention. This proposal seeks to address this knowledge gap in a topic of profound public health significance.

一项里程碑式的研究表明，收缩压干预试验(SPRINT)表明， 降低收缩压(SBP目标值120与140毫米汞柱)可降低死亡风险 无糖尿病但心血管风险高的人群发生重大心血管事件。在最近的一份出版物中， 我们注意到在SPRINT中密集的SBP降低导致估计的肾小球的相对平均下降。 6个月后−滤过率(强化与标准)分别为3.31±0.30mL/min/1.73m2。集约化 SBP组发生慢性肾脏疾病(CKD)的风险也是前者的3.5倍。 2×2糖尿病血压(ACCORD-BP)试验对控制心血管风险的作用 析因设计，测试与Sprint相同的SBP干预，以及强化血糖与标准血糖 2型糖尿病(T2 DM)患者的糖化血红蛋白(GHb)为6%，而不是7.0%至7.8%。在我们的 分析ACCORD-BP数据，强度SBP组与标准SBP组的比较显示 ACCORD-BP的密集SBP干预导致早期平均EGFR下降更加明显， 与Sprint相比，慢性肾脏病的累积发病率增加更多(交互作用p值和lt；0.001)。 由于血压降低导致的EGFR下降可能具有不同的临床和公众特征。 与由于其他情况导致的EGFR下降相比的健康后果，我们已经假设 与内源性肾脏疾病的进展有关。由于跟踪期太短，无法确定 急性早期EGFR下降/CKD事件对硬终点的长期影响，保存的标本来自 研究提供了一个机会来研究对反映关键结果领域的代谢标志物的平行影响 炎症/铁代谢、骨和矿物质代谢/血管钙化。 在此，我们建议研究急性早期EGFR下降/事件的长期代谢影响。 Sprint和ACCORD-BP的CKD。《目标1》的分析将涉及#年急剧变化的后果。 由于SBP干预导致的EGFR和事件CKD以及GFR变化的后果 由于其他因素，包括肾脏疾病的自然病程。目标2将使用现代因果模型 应对EGFR和突发事件CKD的急剧变化的后果的技术 对SBP的强化干预。 目前的提案将澄清EGFR和CKD事件的变化是否伴随着密集的SBP 降低会导致新陈代谢环境的改变。在Sprint之前，没有RCT水平的证据表明密集 将SBP控制在120毫米汞柱的目标可以延长生存期，降低心血管事件的风险。而当 斯普林特发现新奇且意义重大，有人担心斯普林特对肾脏的影响 干预。这项提议试图在一个深刻的公共卫生话题中解决这一知识鸿沟 意义。

项目成果

SPRINT Revisited: Updated Results and Implications.

• DOI: 10.1161/hypertensionaha.121.17682
• 发表时间: 2021-12
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Wright JT Jr;Whelton PK;Johnson KC;Snyder JK;Reboussin DM;Cushman WC;Williamson JD;Pajewski NM;Cheung AK;Lewis CE;Oparil S;Rocco MV;Beddhu S;Fine LJ;Cutler JA;Ambrosius WT;Rahman M;Still CH;Chen Z;Tatsuoka C;SPRINT Research Group
• 通讯作者: SPRINT Research Group

Associations of Hyponatremia with Cognition Function and All-Cause Mortality: Post Hoc Analysis of the Systolic BP Intervention Trial.

• DOI: 10.34067/kid.0000000000000224
• 发表时间: 2023-10-01
• 期刊: Kidney360
• 作者: Sarwal A;Boucher RE;Abraham N;Singh R;Ye X;Moghaddam FA;Hartsell SE;Wei G;Beddhu S
• 通讯作者: Beddhu S

Insulin use in chronic kidney disease and the risk of hypoglycemic events.

• DOI: 10.1186/s12882-022-02687-w
• 发表时间: 2022-02-21
• 期刊: BMC nephrology
• 影响因子: 2.3
• 作者: Grube D;Wei G;Boucher R;Abraham N;Zhou N;Gonce V;Carle J;Simmons DL;Beddhu S
• 通讯作者: Beddhu S

Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.

基线舒张压对收缩压降低对 2 型糖尿病认知功能的影响。

• DOI: 10.1093/ajh/hpac118
• 发表时间: 2023
• 期刊: American journal of hypertension
• 影响因子: 3.2
• 作者: Gupta,Aditi;Boucher,Robert;Wei,Guo;Gronseth,Gary;Parks,Adam;Beddhu,Srinivasan
• 通讯作者: Beddhu,Srinivasan

Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants.

• DOI: 10.1371/journal.pone.0203305
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Supiano MA;Lovato L;Ambrosius WT;Bates J;Beddhu S;Drawz P;Dwyer JP;Hamburg NM;Kitzman D;Lash J;Lustigova E;Miracle CM;Oparil S;Raj DS;Weiner DE;Taylor A;Vita JA;Yunis R;Chertow GM;Chonchol M
• 通讯作者: Chonchol M