估计的肾小球滤过率(eGFR)是心力衰竭的关键参数。人们对管状功能的重要性知之甚少。我们讨论了管状最大磷酸盐再吸收能力(TmP/GFR)的影响,近端管状功能的参数,心力衰竭患者。
我们在2085例心力衰竭患者中建立了TmP/GFR(Bijvoet公式),并研究了其与肾功能恶化(eGFR比基线下降>25%)和血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)倍增(基线至9个月)的相关性。此外,我们使用协方差分析评估了依帕列净抑制钠-葡萄糖转运蛋白2(SGLT2)对78例急性心力衰竭患者肾小管最大磷酸盐再吸收能力的影响.
在1392例(67%)和21例(27%)患者中观察到低TmP/GFR(<0.80mmol/L)。TmP/GFR较低的患者有更晚期的心力衰竭,较低的eGFR,和更高水平的肾小管损伤标记。TmP/GFR较低的主要决定因素是尿素排泄分数较高(P<0.001)。较低的TmP/GFR与血浆NGAL倍增风险较高独立相关(比值比,2.20;95%置信区间,1.05至4.66;P=0.04),但与肾功能恶化无关。较低的TmP/GFR与较高的全因死亡率风险相关(风险比,2.80;95%置信区间,1.37至5.73;P=0.005),心力衰竭住院(危险比,2.29;95%置信区间,1.08至4.88;P=0.03),及其组合(危险比,1.89;95%置信区间,1.07至3.36;P=0.03)经过多变量调整。与安慰剂相比,Empagliflozin在1天后显着增加TmP/GFR(P=0.004),但在调整eGFR变化后没有。
TmP/GFR,测量近端管状功能,经常减少心力衰竭,尤其是晚期心力衰竭患者。此外,较低的TmP/GFR与未来血浆NGAL加倍的风险和更差的临床结果相关。独立于肾小球功能。
The estimated glomerular filtration rate (eGFR) is a crucial parameter in heart failure. Much less is known about the importance of tubular function. We addressed the effect of tubular maximum phosphate reabsorption capacity (TmP/GFR), a parameter of proximal tubular function, in patients with heart failure.
We established TmP/GFR (Bijvoet formula) in 2085 patients with heart failure and studied its association with deterioration of kidney function (>25% eGFR decrease from baseline) and plasma neutrophil gelatinase-associated lipocalin (NGAL) doubling (baseline to 9 months) using logistic regression analysis and clinical outcomes using Cox proportional hazards regression. Additionally, we evaluated the effect of sodium-glucose transport protein 2 (SGLT2) inhibition by empagliflozin on tubular maximum phosphate reabsorption capacity in 78 patients with acute heart failure using analysis of covariance.
Low TmP/GFR (<0.80 mmol/L) was observed in 1392 (67%) and 21 (27%) patients. Patients with lower TmP/GFR had more advanced heart failure, lower eGFR, and higher levels of tubular damage markers. The main determinant of lower TmP/GFR was higher fractional excretion of urea (P<0.001). Lower TmP/GFR was independently associated with higher risk of plasma NGAL doubling (odds ratio, 2.20; 95% confidence interval, 1.05 to 4.66; P=0.04) but not with deterioration of kidney function. Lower TmP/GFR was associated with higher risk of all-cause mortality (hazard ratio, 2.80; 95% confidence interval, 1.37 to 5.73; P=0.005), heart failure hospitalization (hazard ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P=0.03), and their combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36; P=0.03) after multivariable adjustment. Empagliflozin significantly increased TmP/GFR compared with placebo after 1 day (P=0.004) but not after adjustment for eGFR change.
TmP/GFR, a measure of proximal tubular function, is frequently reduced in heart failure, especially in patients with more advanced heart failure. Lower TmP/GFR is furthermore associated with future risk of plasma NGAL doubling and worse clinical outcomes, independent of glomerular function.