The renal tubular defect of Bartter's syndrome.

The site of reduced electrolyte transport in Bartter's syndrome (BS) was studied with a new technique whereby resorption can be separately measured as equivalent volumes of free water generated along the ascending limb of Henle's loop (CH2O-HL) and cortical distal tubule (CH2O-DT): the fractional proximal resorption (FPR) and the volume of free water dissipated along collecting ducts (CD) by back diffusion (CH2O-BD) in the absence of ADH are also measured during maximal water diuresis. Data are expressed as ml . min-1 GFR-1 . 100. The studies were performed on 2 brothers with all clinical and laboratory features of BS. They achieved external Na balance within 3 days when placed on either 10, 100, or 230 mEq Na daily. With the 100-mEq-Na diet indomethacin caused a stable 1.5 kg weight gain. FPR was 0.69 in normal controls (NC), 0.77 in BS; CH2O-HL 16.7 vs. 16.4; CH2O-DT 9.7 vs. 3.9; CH2O-BD 13.8 vs. 13.8; CH2O (free water excretion) 12.5 vs. 6.1; urine flow rate (V) 17.6 vs. 9.9. Thus, BS is characterized by a slight fall in proximal delivery, normal HLNa transport, a striking impairment of DTNa transport and preserved interstitial hypertonicity which drives a normal osmotic flow of CH2O-BD. Aspirin injected intravenously during water load affected CH2O and V in proportion to the change in GFR, which fell from 145 +/- 19 to 114 +/- 12 ml . min-1, p less than 0.01). Thus, the primary abnormality of BS is impaired Na transport along the early portion of the distal tubule. This is compensated by volume contraction attended by reduced proximal delivery and full activation of renin-angiotensin-aldosterone system. Consequently, more distal cation exchange sites reclaim Na+ at the expenses of excessive K+ and H+ losses, trapping NH4Cl within tubular lumen and generating hypokalemic metabolic alkalosis. The excess angiotensin is counterbalanced by increased prostaglandin (PG) secretion, which brings renal vascular resistances toward normal and causes tachyphylaxis to angiotensin. Inhibition of PG synthesis leads to a fall in GFR and proximal delivery: this causes distal delivery to fall below reabsorptive capacity for Na: therefore both Na and K retention ensues causing partial volume reexpansion till a new balance is established. PGs do not affect either Na or Cl resorption in BS except by a purely hemodynamic action.