Colussi G, Rombolà G, Verde G, Airaghi C, Loli P, Minetti L
Division of Nephrology and Dialysis, Niguarda-Ca'Granda Hospital, Milan, Italy.
Am J Nephrol. 1992;12(4):229-39. doi: 10.1159/000168451.
Five patients with the clinical patterns of Bartter's syndrome underwent a series of clearance studies in order to characterize the underlying tubule defect. Free water generation during maximal water diuresis (CH2O), expressed as percentage of the distal delivery (CH2O + CCl), was lower in the patients (72.5 +/- 3.2%) than in controls (84.4 +/- 5.5, p < 0.0001). During maximal water diuresis and furosemide administration (40 mg i.v. as bolus), NaCl reabsorption along the diluting nephron segments could be separated into 2 components, that occurring in the loop of Henle (DRNaHL) and that occurring in tubule segments beyond the macula densa (DRNaDT): DRNaHL was normal, while DRNaDT was reduced (3.1 +/- 0.8 vs. 6.2 +/- 2.5 ml/min in controls, p < 0.015). Thus, according to this furosemide protocol, our patients had normal solute reabsorption in the loop of Henle but reduced NaCl reabsorption in tubule segments beyond the macula densa. During 0.9% saline infusion (2 liters in 2 h, after stimulation of distal Na reabsorption with fludrocortisone) fractional excretion (FE) of K showed a linear rise with the increase of FECl-FEK, however, was much higher in the patients than in controls for every FECl level. In contrast, the infusion of Na2SO4, after fludrocortisone administration, induced similar FEK increases in patients and in controls. Thus, in these patients Na reabsorption in the distal nephron (possibly the cortical collecting tubule) was associated with the generation of a higher than normal electric potential gradient in the presence of Cl but not of another poorly reabsorbable anion, such as SO4(2-). These observations indicate that, in our patients, Henle's loop function is normal, while the collecting tubule function is abnormal. We suggest that NaCl wasting and enhanced tubular secretion of H+ and K in our patients might result from an abnormally low conductance to Cl in distal nephron site(s) where Na reabsorption is electrogenic, possibly the cortical collecting tubule. A larger than normal transtubular electric gradient would be generated by Na reabsorption, causing: (1) a direct stimulation of tubular secretion of K and H+ (leading to hypokalemia and alkalosis) and (2) inhibition of the reabsorption of Na ('trapped' into the tubular lumen by electric forces), with consequent extracellular volume contraction, hyperreninemia and hyperaldosteronism.
5例具有巴特综合征临床症状的患者接受了一系列清除率研究，以明确潜在的肾小管缺陷。最大水利尿期间的自由水生成率（CH2O），以远端输送量（CH2O + CCl）的百分比表示，患者（72.5 +/- 3.2%）低于对照组（84.4 +/- 5.5，p < 0.0001）。在最大水利尿和静脉推注速尿（40mg）期间，沿稀释性肾单位节段的NaCl重吸收可分为2个部分，即发生在髓袢的部分（DRNaHL）和发生在致密斑远端肾小管节段的部分（DRNaDT）：DRNaHL正常，而DRNaDT降低（患者为3.1 +/- 0.8ml/min，对照组为6.2 +/- 2.5ml/min，p < 0.015）。因此，根据该速尿方案，我们的患者髓袢溶质重吸收正常，但致密斑远端肾小管节段的NaCl重吸收降低。在输注0.9%盐水（2小时内输注2升，在用氟氢可的松刺激远端Na重吸收后）期间，K的分数排泄率（FE）随FECl - FEK的增加呈线性上升，然而，在每个FECl水平下，患者的FEK均远高于对照组。相反，在给予氟氢可的松后输注Na2SO4，患者和对照组的FEK升高相似。因此，在这些患者中，远端肾单位（可能是皮质集合管）的Na重吸收在存在Cl时会产生高于正常的电位梯度，但在存在另一种不易重吸收的阴离子如SO4(2-)时则不会。这些观察结果表明，在我们的患者中，髓袢功能正常，而集合管功能异常。我们认为，我们患者的NaCl丢失以及H+和K的肾小管分泌增加可能是由于远端肾单位部位（可能是皮质集合管）对Cl的电导率异常降低所致，在该部位Na重吸收是电生性的。Na重吸收会产生大于正常的跨肾小管电位梯度，导致：（1）直接刺激肾小管分泌K和H+（导致低钾血症和碱中毒），以及（2）抑制Na的重吸收（被电力“困”在肾小管腔内），从而导致细胞外液量减少、高肾素血症和高醛固酮血症。
