Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland.
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Pflugers Arch. 2018 Feb;470(2):427-438. doi: 10.1007/s00424-017-2049-0. Epub 2017 Aug 12.
It is well known that pendrin, an apical Cl/HCOexchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NHCl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH excretion. Nadir urinary pH was achieved 5 h after NHCl loading. Exosomal pendrin abundance was dramatically decreased at 3 h after acid loading. In contrast, after acute equimolar oral NaHCO loading (n = 8), urinary and venous blood pH rose rapidly with a significant attenuation of urinary NH excretion. Alkali loading caused rapid upregulation of exosomal pendrin abundance at 1 h and normalized within 3 h of treatment. Equimolar NaCl loading (n = 6) did not alter urinary or venous blood pH or urinary NH excretion. However, pendrin abundance in urinary exosomes was significantly reduced at 2 h of NaCl ingestion with lowest levels observed at 4 h after treatment. In patients with inherited distal renal tubular acidosis (dRTA), pendrin abundance in urinary exosomes was greatly reduced and did not change upon oral NHCl loading. In summary, pendrin can be detected and quantified in human urinary exosomes by immunoblotting. Acid, alkali, and NaCl loadings cause acute changes in pendrin abundance in urinary exosomes within a few hours. Our data suggest that exosomal pendrin is a promising urinary biomarker for acute acid-base and volume status changes in humans.
众所周知，顶端 Cl/HCO3-交换器 pendrin 在 B 型闰细胞中受慢性酸碱平衡紊乱和电解质摄入的调节。为了在急性水平上进一步研究这种适应性，我们分析了接受口服急性酸、碱和 NaCl 负荷的个体的尿外泌体。急性口服 NH4Cl 负荷（n=8）引起全身酸中毒，尿 pH 值下降，尿 NH4 排泄增加。NH4Cl 负荷后 5 小时达到尿 pH 值最低点。酸负荷后 3 小时，外泌体 pendrin 丰度显著降低。相比之下，在急性等摩尔口服 NaHCO3 负荷后（n=8），尿和静脉血 pH 值迅速升高，尿 NH4 排泄显著减少。碱负荷在 1 小时引起外泌体 pendrin 丰度的快速上调，并在治疗 3 小时内恢复正常。等摩尔 NaCl 负荷（n=6）未改变尿或静脉血 pH 值或尿 NH4 排泄。然而，NaCl 摄入 2 小时后尿外泌体中 pendrin 的丰度显著降低，治疗后 4 小时观察到最低水平。在遗传性远端肾小管酸中毒（dRTA）患者中，尿外泌体中的 pendrin 丰度显著降低，口服 NH4Cl 负荷后不会改变。总之，免疫印迹法可检测和定量人尿外泌体中的 pendrin。酸、碱和 NaCl 负荷在数小时内引起尿外泌体中 pendrin 丰度的急性变化。我们的数据表明，外泌体 pendrin 是一种有前途的人类急性酸碱和容量状态变化的尿生物标志物。
