Hinrichs Gitte Rye, Nielsen Jette Rude, Birn Henrik, Bistrup Claus, Jensen Boye Lagerbon
Department of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
Department of Nephrology, Odense University Hospital, Odense, Denmark.
Am J Physiol Renal Physiol. 2023 Oct 1;325(4):F426-F435. doi: 10.1152/ajprenal.00108.2023. Epub 2023 Aug 10.
Albuminuria in kidney transplant recipients (KTRs) is associated with hypertension and aberrant glomerular filtration of serine proteases that may proteolytically activate the epithelial Na channel (ENaC). The present nonrandomized, pharmacodynamic intervention study aimed to investigate if inhibition of ENaC increases Na excretion and reduces extracellular volume in KTRs dependent on the presence of albuminuria. KTRs with and without albuminuria (albumin-to-creatinine ratio > 300 mg/g, = 7, and <30 mg/g, = 7, respectively) were included and ingested a diet with fixed Na content (150 mmol/day) for 5 days. On the last day, amiloride at 10 mg was administered twice. Body weight, 24-h urine electrolyte excretion, body water content, and ambulatory blood pressure as well as plasma renin, angiotensin II, and aldosterone concentrations were determined before and after amiloride. Amiloride led to a significant decrease in body weight, increase in 24-h urinary Na excretion, and decrease in 24-h urinary K excretion in both groups. Urine output increased in the nonalbuminuric group only. There was no change in plasma renin, aldosterone, and angiotensin II concentrations after amiloride, whereas a significant decrease in nocturnal systolic blood pressure and increase in 24-h urine aldosterone excretion was observed in albuminuric KTRs only. There was a significant correlation between 24-h urinary albumin excretion and amiloride-induced 24-h urinary Na excretion. In conclusion, ENaC activity contributes to Na and water retention in KTRs with and without albuminuria. ENaC is a relevant pharmacological target in KTRs; however, larger and long-term studies are needed to evaluate whether the magnitude of this effect depends on the presence of albuminuria. Amiloride has a significant natriuretic effect in kidney transplant recipients (KTRs) that relates to urinary albumin excretion. The epithelial Na channel may be a relevant direct pharmacological target to counter Na retention and hypertension in KTRs. Epithelial Na channel blockers should be further investigated as a mean to mitigate Na and water retention and to potentially obtain optimal blood pressure control in KTRs.
肾移植受者（KTRs）的蛋白尿与高血压以及丝氨酸蛋白酶异常的肾小球滤过有关，丝氨酸蛋白酶可能通过蛋白水解作用激活上皮钠通道（ENaC）。本项非随机、药效学干预研究旨在探讨抑制ENaC是否能增加KTRs的钠排泄并减少细胞外液量，这取决于蛋白尿的存在情况。纳入了有蛋白尿和无蛋白尿的KTRs（白蛋白与肌酐比值分别>300mg/g，n = 7，以及<30mg/g，n = 7），并让他们摄入固定钠含量（150mmol/天）的饮食5天。在最后一天，给予10mg氨氯吡咪，分两次服用。在服用氨氯吡咪前后，测定体重、24小时尿电解质排泄、身体含水量、动态血压以及血浆肾素、血管紧张素II和醛固酮浓度。氨氯吡咪导致两组的体重显著下降、24小时尿钠排泄增加以及24小时尿钾排泄减少。仅在无蛋白尿组尿量增加。服用氨氯吡咪后血浆肾素、醛固酮和血管紧张素II浓度无变化，而仅在有蛋白尿的KTRs中观察到夜间收缩压显著下降以及24小时尿醛固酮排泄增加。24小时尿白蛋白排泄与氨氯吡咪诱导的24小时尿钠排泄之间存在显著相关性。总之，ENaC活性促成了有蛋白尿和无蛋白尿的KTRs中的钠和水潴留。ENaC是KTRs中一个相关的药理学靶点；然而，需要更大规模的长期研究来评估这种效应的程度是否取决于蛋白尿的存在。氨氯吡咪在肾移植受者（KTRs）中具有显著的利钠作用，这与尿白蛋白排泄有关。上皮钠通道可能是对抗KTRs中钠潴留和高血压的一个相关直接药理学靶点。上皮钠通道阻滞剂应作为减轻KTRs中钠和水潴留并潜在实现最佳血压控制的手段进行进一步研究。
