Impaired diluting segment chloride reabsorption in patients with cystic fibrosis.

Clearance studies were performed in 12 patients with cystic fibrosis (CF) during maximum water diuresis. The fractional diluting segment reabsorption was calculated from chloride clearance (CCl) and maximum free water clearance (CH2O) as 'CH2O/CCl+CH2O'. Fractional delivery to the diluting segment and from the proximal tubules was estimated by maximum urine flow during water diuresis (Vmax/GFR) and lithium clearance (CLi/GFR), respectively. The data were compared with results obtained in young healthy subjects. To estimate free water generation beyond the medullary diluting segment, CH2O/GFR was also measured during acute furosemide administration in 5 patients. Values for the term CH2O/CCl+CH2O were significantly lower in patients with CF (79.1 +/- 5.1%) as compared with healthy controls (89.4 +/- 4.4%). This was also true for the terms Vmax/GFR (CF: 9.5 +/- 1.6%; control subjects: 13.8 +/- 2.5%) and CLi/GFR (CF: 22.2 +/- 4.1%; control subjects: 30.7 +/- 5.1%). Compared to data derived from the literature, the solute-free water generation during administration of furosemide (CH2O/GFR) was significantly reduced in patients with CF (6.8 +/- 1.5%) as compared with healthy subjects (13.3 +/- 6.1%). We conclude that reabsorption in the diluting segment is impaired in patients with CF, perhaps at a site beyond the thick ascending limb of Henle's loop. Enhanced proximal reabsorption, suggested by reductions in Vmax/GFR and CLi/GFR, appears to be a compensatory phenomenon to maintain sodium and chloride balance.