The present study was designed to characterize the effects of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) on sodium handling by surface nephrons, deep nephrons and the terminal collecting duct segment. Studies were performed in rats during hydropenia and volume expansion. In hydropenia, the glomerular filtration rate (GFR) and sodium excretion tended to be lower in rats with GN than in controls. However, the major differences between the control and GN animals were seen in volume expansion. In the volume expanded groups fractional excretion of sodium was greater in controls (3.20 +/- 0.51%) than in GN (1.20 +/- 0.36%, P less than 0.01). Despite this, delivery to end proximal sites was similar in the two groups in absolute terms and higher in the expanded GN group compared to the expanded controls. Absolute sodium delivery to the bend of the loop of Henle in the expanded GN rats was decreased in absolute terms but increased in fractional terms compared to expanded controls. However, fractional delivery of sodium to the base of the terminal collecting duct was less in GN (3.71 +/- 1.39%) than in controls (7.19 +/- 0.96%, P less than 0.002). In both groups, fractional delivery between tip of the collecting duct fell compared to base (P less than 0.05) but delivery to the tip was again greater in controls (5.49 +/- 1.08%) than in GN (1.51 +/- 0.47%). In GN 62.6 +/- 5.0% of delivered sodium was reabsorbed between collecting duct sites, nearly twofold that of controls (28.8 +/- 9.4%, P less than 0.01). Thus, fractional sodium reabsorption in the collecting duct was enhanced by GN.

The present study examined the contribution of individual superficial nephron segments to sodium excretion in antiglomerular basement membrane nephritis in the rat by sampling the same nephron successively from the end and beginning of the distal tubule and end of the proximal tubule. Whole kidney GFR in glomerulonephritic rats was reduced by approximately 40% from controls; absolute sodium excretion was about 25% of normal. Metabolic balance studies in the awake state had suggested that the animals were in sodium balance. Plasma renin levels before and during micropuncture were similar to controls. These findings suggest that the defect in sodium handling is intrinsic to the kidney. Glomerulotubular balance was maintained along the proximal tubule. Sodium reabsorption in the loop of Henle was reduced in absolute terms but was proportional to the load delivered. Due to the decreased absolute sodium reabsorption in the preceding segments, sodium delivery to the beginning of the distal tubule was comparable in the two groups of animals. Along the distal tubule sodium reabsorption was comparable to control animals. Therefore, the avid urinary sodium retention seen during micropuncture was due to increased sodium reabsorption by segments past the superficial proximal tubule and/or by deep nephrons.

The renal adaptations that maintain potassium homeostasis in diffuse forms of glomerular disease are not well defined. Thus, handling of potassium by superficial nephron segments was examined in a rat model of antiglomerular basement membrane nephritis. Sampling the same nephron successively from the end and beginning of the distal tubule and the end of the proximal tubule allowed a segmental analysis. Despite a 40% reduction in GFR, potassium excretion in the glomerulonephritis animals was normal due to an increase in FEK. The proximal tubule and loop segment did not contribute to the enhanced FEK seen in these animals. In contrast, potassium entry along the distal tubule was significantly greater in the experimental group averaging 13.7 +/- 4.3 pmol/min compared to 1.2 +/- 1.7 pmol/min in controls (P less than 0.01). Multiple linear regression analysis showed that distal tubule potassium entry at any level of flow was enhanced in glomerulonephritis compared to controls (P less than 0.0001). Plasma aldosterone levels were similar in both groups of animals. Thus, the adaptation to potassium excretion seen in glomerulonephritis is partly achieved by the distal tubule through flow-rate independent mechanisms and appears to be independent of plasma aldosterone levels.

Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled. As anticipated, the ammonium concentration (TFNH+4) was significantly higher in proximal tubule fluid during acidosis, and ammonium delivery to end proximal sites increased from 19.4 +/- 2.3 to 34.0 +/- 3.2 pmol/min (P less than 0.001). Although chronic acidosis did not affect TFNH+4 at the beginning of the distal tubule, ammonium delivery to the end of the distal tubule increased from 5.72 +/- 0.97 to 9.88 +/- 0.97 pmol/min. In both control and acidotic groups ammonium delivery was lower (P less than 0.001) to end distal sites than to end proximal sites, indicating net loss in the intervening segment. This loss was greater during chronic metabolic acidosis (23.9 +/- 3.3 vs. 13.6 +/- 2.0 pmol/min in controls, P less than 0.025). In both groups net entry of ammonia, in similar amounts, occurred along the distal tubule (P less than 0.05). In situ pH averaged 6.80 +/- 0.05 at end proximal tubule sites and fell to 6.54 +/- 0.08 at the beginning of the distal tubule (P less than 0.005). Chronic metabolic acidosis did not affect these measurements. The calculated free ammonia at the end of the proximal tubule rose from 9.3 +/- 2.2 to 21 +/- 9 microM (P less than 0.005) during chronic metabolic acidosis, and was also higher at beginning distal sites during acidosis (8.8 +/- 2.4 vs. 2.7 +/- 0.7 microM in controls, P less than 0.05). In both groups ammonia values for the beginning distal tubule fluid were lower than for end proximal tubule fluid. Thus, loss of ammonium in the loop segment is enhanced by chronic metabolic acidosis. Distal entry of ammonia is markedly less than along the proximal tubule and does not change in chronic metabolic acidosis, and ammonia permeabilities for the proximal and distal segments of surface nephrons seem different.

Nonionic diffusion and diffusion equilibrium of ammonia have been generally accepted as the mechanism of urinary ammonium excretion. However, these characteristics have not been examined directly in vitro. In the present studies, nonionic diffusion and diffusion equilibrium of ammonia were examined in rabbit cortical collecting tubules perfused in vitro. Collected fluid ammonium and pH were measured in tubules exposed to chemical gradients of NH3/NH+4. In tubules perfused with an acid perfusate free of ammonia and bathed with solutions containing NH4Cl, collected fluid ammonia failed to equilibrate across the epithelium except at slow flow rates. The estimated apparent permeability coefficient to NH3 was approximately 5 X 10(-3) cm/s. Predominant nonionic diffusion of NH3, rather than transport of NH+4, was indicated by alkalinization of luminal fluid in tubules exposed to peritubular NH4Cl and by the relative influence of peritubular NH+4 and NH3 on ammonia entry. In tubules perfused with an acid solution containing NH4Cl, little loss of ammonium was detectable, indicating a low permeability to NH+4. In contrast to the restricted diffusion of NH3 in cortical collecting tubules, proximal convoluted tubules exhibited a much higher apparent permeability to NH3. In conclusion, nonionic diffusion of NH3 accounted for most ammonium transport in the proximal convoluted tubule and in the cortical collecting tubule. However, there was relatively restricted diffusion in the collecting tubules; this may account for the failure of whole kidney ammonium excretion to obey quantitatively the predictions of nonionic diffusion and diffusion equilibrium of ammonia.