Dörr Katharina, Kammer Michael, Reindl-Schwaighofer Roman, Lorenz Matthias, Marculescu Rodrig, Poglitsch Marko, Beitzke Dietrich, Oberbauer Rainer
Department of Nephrology, Medical University of Vienna, Vienna, Austria.
Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
Front Med (Lausanne). 2022 Apr 26;9:878730. doi: 10.3389/fmed.2022.878730. eCollection 2022.
Fibroblast growth factor 23 (FGF23) is elevated in patients with chronic kidney disease and contributes to left ventricular hypertrophy (LVH). The aim of the analysis was to determine whether this effect is mediated by the renin-angiotensin-aldosterone system (RAAS) in hemodialysis. Serum samples from 62 randomized hemodialysis patients with LVH were analyzed for plasma renin activity (PRA-S), angiotensin II (AngII), and metabolites, angiotensin-converting enzyme-2 (ACE2) and aldosterone using a high throughput mass spectrometry assay. Compared to healthy individuals, levels of the RAAS parameters PRA-S, AngII and aldosterone were generally lower [median (IQR) PRA-S 130 (46-269) vs. 196 (98, 238) pmol/L; AngII 70 (28-157) vs. 137 (76, 201) pmol/L; Aldosterone 130 (54, 278) vs. 196 (98, 238) pmol/L]. We did not find an indication that the effect of FGF23 on LVH was mediated by RAAS parameters, with all estimated indirect effects virtually zero. Furthermore, FGF23 was not associated with RAAS parameter levels throughout the study. While there was a clear association between FGF23 levels and left ventricular mass index (LVMI) at the end of the study and in the FGF23 fold change and LVMI change analysis, no association between RAAS and LVMI was observed. Serum concentrations of PRA-S, AngII, and aldosterone were below the ranges measured in healthy controls suggesting that RAAS is not systemically activated in hemodialysis patients. The effect of FGF23 on LVMI was not mediated by systemic RAAS activity. These findings challenge the current paradigm of LVH progression and treatment with RAAS blockers in dialysis.
[https://clinicaltrials.gov/ct2/show/NCT03182699], identifier [NCT03182699].
慢性肾脏病患者的成纤维细胞生长因子23（FGF23）水平升高，且与左心室肥厚（LVH）有关。本分析的目的是确定这种作用在血液透析中是否由肾素 - 血管紧张素 - 醛固酮系统（RAAS）介导。使用高通量质谱分析法对62例随机分组的患有LVH的血液透析患者的血清样本进行血浆肾素活性（PRA - S）、血管紧张素II（AngII）及其代谢产物、血管紧张素转换酶2（ACE2）和醛固酮的分析。与健康个体相比，RAAS参数PRA - S、AngII和醛固酮的水平普遍较低[中位数（四分位间距）PRA - S 130（46 - 269）对比196（98，238）pmol/L；AngII 70（28 - 157）对比137（76，201）pmol/L；醛固酮130（54，278）对比196（98，238）pmol/L]。我们未发现FGF23对LVH的作用由RAAS参数介导的迹象，所有估计的间接效应几乎为零。此外，在整个研究过程中，FGF23与RAAS参数水平无关。虽然在研究结束时FGF23水平与左心室质量指数（LVMI）之间以及在FGF23倍数变化和LVMI变化分析中有明显关联，但未观察到RAAS与LVMI之间的关联。PRA - S、AngII和醛固酮的血清浓度低于健康对照者测得的范围，表明血液透析患者的RAAS未被全身激活。FGF23对LVMI的作用并非由全身RAAS活性介导。这些发现挑战了目前关于LVH进展及在透析中使用RAAS阻滞剂进行治疗的范式。
[https://clinicaltrials.gov/ct2/show/NCT03182699]，标识符[NCT03182699]。
