Loss of tubuloglomerular feedback in decompensated liver cirrhosis:: Physiopathological implications
Loss of tubuloglomerular feedback in decompensated liver cirrhosis:: Physiopathological implications
复制标题
DOI：
10.1007/s10620-005-2671-0
复制
发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Rizzetto, M
中科院分区：
文献类型：
--
作者：
Sansoè, G;Silvano, S;Rizzetto, M
在健康受试者中，动脉压降低或肾缺血通过自动调节和肾小球反馈（TuGF）导致肾动脉扩张。失代偿性肝硬化患者的肾脏灌注压降低，但表现出肾血管收缩，而不是自动调节介导的血管舒张。本研究探讨了代偿性和腹水性非氮质性肝硬化患者肾脏自动调节功能丧失对肾脏灌注、肾小球滤过率和肾小管电解质处理的影响。对 42 名连续的无利尿剂肝硬化患者（32 名腹水前患者和 10 名腹水病患者）和 10 名对照进行以下测定： (a) 基础血浆肾素活性和醛固酮水平； (b) 内源性多巴胺能活性，以甲氧氯普胺给药期间增量醛固酮反应测量； (c)钠、钾、菊粉、对氨基马尿酸和锂的肾清除率。与其他组相比，腹水患者表现出较低的肾血浆流量（P < 0.01）和锂清除率（P < 0.05），较高的滤过分数（P < 0.01）和继发性醛固酮增多症。对照组和前腹水患者表现出肾小管肾小球反馈（当到达远端肾小管的钠负荷减少时，肾小球滤过率增加的机制），锂排泄分数（钠向远端肾单位输送的分数的表达）与肾小球滤过率之间的负相关性证明了这一点（分别为，r = -0.73，P < 0.03，和 r = -0.48，P < 0.01）。相反，腹水患者的锂排泄分数与肾小球滤过率呈正相关（r = 0.64，P < 0.05）。失代偿患者中发现的肾灌注减少、滤过分数增加和 TuGF 紊乱表明普遍存在肾小球后小动脉血管收缩，从而刺激近端肾小管钠重吸收。
In healthy subjects, arterial pressure reduction or renal ischemia produces renal artery dilatation through autoregulation and tubuloglomerular feedback (TuGF). Patients with decompensated cirrhosis have reduced kidney perfusion pressure but show renal vasoconstriction instead of autoregulation-mediated vasodilation. This study investigates the consequences of kidney autoregulation loss on renal perfusion, glomerular filtration rate, and tubular handling of electrolytes in both compensated and ascitic nonazotemic cirrhotic patients. Forty-two consecutive patients with diuretic-free liver cirrhosis (32 with preascitic and 10 with ascitic disease) and 10 controls were submitted to the following determinations: (a) basal plasma renin activity and aldosterone levels; (b) endogenous dopaminergic activity measured as incremental aldosterone responses during metoclopramide administration; and (c) renal clearances of sodium, potassium, inulin, para-aminohippurate and lithium. Compared with the other groups, ascitic patients showed lower renal plasma flow (P < 0.01) and lithium clearance (P < 0.05), a higher filtration fraction (P < 0.01), and secondary aldosteronism. Controls and preascitic patients displayed tubuloglomerular feedback (the mechanism increasing the glomerular filtration rate when a reduced sodium load reaches the distal tubule), as demonstrated by negative correlations between fractional excretion of lithium (an expression of fractional delivery of sodium to the distal nephron) and glomerular filtration rate (respectively, r = -0.73, P < 0.03, and r = -0.48, P < 0.01). Conversely, patients with ascites showed a positive correlation between lithium fractional excretion and glomerular filtration rate (r = 0.64, P < 0.05). Reduction in renal perfusion, increased filtration fraction, and TuGF derangement, as found in decompensated patients, are indicative of prevalent postglomerular arteriolar vasoconstriction, with ensuing stimulation of proximal tubular sodium reabsorption.