Estimated Kidney Tubular Secretion and Kidney, Cardiovascular, and Mortality Outcomes in CKD: The Systolic Blood Pressure Intervention Trial.
Estimated Kidney Tubular Secretion and Kidney, Cardiovascular, and Mortality Outcomes in CKD: The Systolic Blood Pressure Intervention Trial.
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DOI：
10.1016/j.xkme.2022.100546
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发表时间：
2022-12
期刊：
影响因子：
3.9
通讯作者：
Garimella, Pranav S.
中科院分区：
文献类型：
--
作者：
Ascher, Simon B.;Shlipak, Michael G.;Katz, Ronit;Bullen, Alexander L.;Scherzer, Rebecca;Hallan, Stein I.;Cheung, Alfred K.;Raphael, Kalani L.;Estrella, Michelle M.;Jotwani, Vasantha K.;Seegmiller, Jesse C.;Ix, Joachim H.;Garimella, Pranav S.
许多药物、代谢物和毒素通过肾小管分泌被肾脏清除。新的内源性肾小管分泌指标是否能提供有关肾脏、心血管和死亡风险的信息尚不确定。临床试验参与者的纵向亚组分析。2，089名基线时估计肾小球滤过率（eGFR）<60 mL/min/1.73 m2的Syringe血压干预试验参与者。汇总评分，包括基线时配对尿液和血浆样本中测量的10种内源性分泌标志物的尿液/血浆比值。主要结局是eGFR的纵向变化。次要结局包括慢性肾脏疾病（CKD）进展（eGFR下降≥50%或需要透析或肾移植的肾衰竭事件）、心血管疾病（CVD）复合终点（心肌梗死、急性冠状动脉综合征、卒中、急性失代偿性心力衰竭或心血管原因死亡）和死亡率。使用线性混合效应模型评价分泌评分与eGFR变化之间的相关性，使用考克斯比例风险模型评价与CKD进展、CVD和死亡率之间的相关性。基线时，平均年龄为73 ± 9岁，eGFR为46 ± 11 mL/min/1.73 m2。在中位随访3.3年期间，eGFR的平均变化为每年-1.44%，发生72例CKD进展事件，272例CVD事件和144例死亡。在多变量分析中，较低的分泌物评分与eGFR下降更快和CKD进展、CVD和死亡率风险更高相关。在进一步校正基线eGFR和白蛋白尿后，分泌评分每降低1个标准差，eGFR下降速度就更快（每年-0.65%; 95% CI，-0.84%至0.46%），但非CKD进展（HR，1.23; 95% CI，0.96-1.58）、CVD（HR，1.02; 95% CI，0.89-1.18）或死亡率（HR，0.90; 95% CI，0.74-1.09）。在基线eGFR <45 mL/min/1.73 m2的参与者中，分泌评分与eGFR下降的相关性更强（相互作用P < 0.001）。排除糖尿病和蛋白尿>1 g/d的人。在患有CKD的SPRINT受试者中，较低的肾小管分泌估计值与eGFR下降较快相关，与基线eGFR和白蛋白尿无关，但与CKD进展、CVD或死亡率无关。
Many drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain. Longitudinal subgroup analysis of clinical trial participants. 2,089 Systolic Blood Pressure Intervention Trial participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline. Summary score incorporating urine-to-plasma ratios of 10 endogenous secretion markers measured in paired urine and plasma samples at baseline. The primary outcome was longitudinal change in eGFR. Secondary outcomes included chronic kidney disease (CKD) progression (≥50% eGFR decline or incident kidney failure requiring dialysis or kidney transplantation), a cardiovascular disease (CVD) composite (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes), and mortality. Linear mixed-effect models were used to evaluate the association between the secretion score and change in eGFR, and Cox proportional hazards models were used to evaluate associations with CKD progression, CVD, and mortality. At baseline, mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.3 years, mean change in eGFR was −1.44% per year, and 72 CKD progression events, 272 CVD events, and 144 deaths occurred. In multivariable analyses, lower secretion score was associated with faster eGFR decline and greater risk of CKD progression, CVD, and mortality. After further adjustment for baseline eGFR and albuminuria, each 1-standard deviation lower secretion score was associated with faster eGFR decline (−0.65% per year; 95% CI, −0.84% to −0.46%), but not CKD progression (HR, 1.23; 95% CI, 0.96-1.58), CVD (HR, 1.02; 95% CI, 0.89-1.18), or mortality (HR, 0.90; 95% CI, 0.74-1.09). The secretion score association with eGFR decline appeared stronger in participants with baseline eGFR <45 mL/min/1.73 m2 (P for interaction < 0.001). Persons with diabetes and proteinuria >1 g/d were excluded. Among SPRINT participants with CKD, lower estimated tubular secretion was associated with faster eGFR decline, independent of baseline eGFR and albuminuria, but not with CKD progression, CVD, or mortality.
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DOI：
10.1056/nejmoa1114248
发表时间：
2012-07-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Inker LA;Schmid CH;Tighiouart H;Eckfeldt JH;Feldman HI;Greene T;Kusek JW;Manzi J;Van Lente F;Zhang YL;Coresh J;Levey AS;CKD-EPI Investigators
通讯作者：
CKD-EPI Investigators
影响因子：
39.3
作者：
Garimella, Pranav S.;Lee, Alexandra K.;Shlipak, Michael G.
通讯作者：
Shlipak, Michael G.
DOI：
10.1177/1740774514537404
发表时间：
2014-10
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Ambrosius WT;Sink KM;Foy CG;Berlowitz DR;Cheung AK;Cushman WC;Fine LJ;Goff DC Jr;Johnson KC;Killeen AA;Lewis CE;Oparil S;Reboussin DM;Rocco MV;Snyder JK;Williamson JD;Wright JT Jr;Whelton PK;SPRINT Study Research Group
通讯作者：
SPRINT Study Research Group
影响因子：
4.2
作者：
Jotwani, Vasantha K.;Lee, Alexandra K.;Ix, Joachim H.
通讯作者：
Ix, Joachim H.
影响因子：
5.5
作者：
Levin, Adeera;Stevens, Paul E.
通讯作者：
Stevens, Paul E.