Distal nephron function in Bartter's syndrome: abnormal conductance to chloride in the cortical collecting tubule?
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.
Colussi
G
G
Division of Nephrology and Dialysis, Niguarda-Ca'Granda Hospital, Milan, Italy.
Rombolà
G
G
Verde
G
G
Airaghi
C
C
Loli
P
P
Minetti
L
L
D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000627:therapeutic use; D001477:Bartter Syndrome / Q000188:drug therapy / Q000378:metabolism*; D004231:Diuresis; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D005665:Furosemide; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012965:Sodium Chloride / Q000493:pharmacokinetics*; D013148:Spironolactone / Q000627:therapeutic use; D013431:Sulfates
D013431:Sulfates; C012036:sodium sulfate; D013148:Spironolactone; D012965:Sodium Chloride; D000584:Amiloride; D005665:Furosemide; D005438:Fludrocortisone