The functional adaptation of the diseased kidney. 3. Ammonium excretion.

Dorhout-Mees, E J; Machado, Marcello; Slatopolsky, Eduardo; Klahr, Saulo; Bricker, Neal S.

doi:10.1172/jci105342

Cited by 46 publications

(18 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study a two-thirds reduction in renal mass affected the capacity of the residual functioning nephrons to excrete acid in ways similar to those described by other investigators in humans (4, 10-13) and in experimental animals (14)(15)(16)(17). That is, the capacity of the RK to excrete acid was significantly impaired and a metabolic acidosis ensued.…”

Section: Discussionsupporting

confidence: 85%

Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat

Buerkert¹,

Martin²,

Trigg³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Papillary and surface micropuncture were used to study the handling of ammonium and the formation of net acid by surface nephrons, deep nephrons, and the terminal segment of collecting duct (CD) after renal mass was reduced by two-thirds. Net acid excretion by the remnant kidney (RK) was significantly reduced, averaging 794±81 neq/min (SE) compared with 1,220±105 neq/min after sham operation (P < 0.001), due to a decrease in ammonium excretion (494±54 vs. 871±79 nmol/min in controls, P < 0.001). Urinary pH and titratable acid excretion were not different in the two groups of animals. After RK formation, ammonium delivery to the end of the proximal tubule increased nearly threefold and averaged 66.2±5.6 compared with 18.4±2.9 pmol/min in controls, (P < 0.001). This greater delivery of ammonium was primarily due to renal tubule entry rather than to changes in the filtered load and was only partially related to the differences in flow rate. Ammonium processing by deep nephrons was profoundly affected by a reduction in renal mass. Although absolute delivery of ammonium was greater to the bend of Henle's loop (BHL), the difference could be accounted for on the basis of an increase in nephron size. Received for publication I November 1982 and in revised form 23 February 1983. with the RK. Hydrogen secretion in the proximal segments of deep and surface nephrons did not increase in proportion to the decrease in renal mass and as a consequence bicarbonate delivery to the end of the proximal tubule of surface nephrons and to the BHL of deep nephrons was increased.When renal mass was reduced FDNH. to the base of the terminal CD doubled but did not change by the tip. In both groups FDNI4+ to the base of the CD was greater than to the end of the distal tubule. However, the increase was the same. On the other hand, the increase in the net acid index between the end of the distal tubule and the base of the CD was profoundly greater in rats with an RK. This difference was primarily due to bicarbonate reabsorption rather than enhanced ammonium reentry. Indeed, >400% of the fractional ammonium delivered to the end of the proximal tubule was lost from the tubule fluid. The data suggest that the decrease in acid excretion by the RK is due to two factors. First, hydrogen secretion in the proximal segments of both nephron populations fails to increase in the proportion to the reduction in renal mass. Second, a reduced reentrapment of ammonia, rather than its impaired production, causes ammonium excretion to decrease.

show abstract

Section: Discussionsupporting

confidence: 85%

Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat

Buerkert¹,

Martin²,

Trigg³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Our study focuses on the adaptive changes in acid excretion in general and ammonia production in particular. In human and experimental chronic renal disease, total urinary ammonium excretion decreases (10,11). However, when corrected for GFR, ammonium excretion increases several fold above control values (10)(11)(12) Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in human and experimental renal disease demonstrate that, despite reductions in total ammonia production, ammonia excretion factored for glomerular filtration rate is increased severalfold (10)(11)(12). Ammonia production per surviving nephron more than doubles in rats with 70% reduction in renal mass (13).…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3.

Nath¹,

1985

View full text Add to dashboard Cite

The human end-stage kidney and its experimental analogue, the remnant kidney in the rat, exhibit widespread tubulointerstitial disease. We investigated whether the pathogenesis of such tubulo-interstitial injury is dependent upon adaptive changes in tubular function and, in particular, in ammonia production when renal mass is reduced. Dietary acid load was reduced in 143nephrectomized rats by dietary supplementation with sodium bicarbonate (NaHCO3), while control rats, paired for serum creatinine after 14 nephrectomy, were supplemented with equimolar sodium chloride. After 4-6 wk, NaHCO3-supplemented rats demonstrated less impairment of tubular function as measured by urinary excretory rates for total protein and low molecular weight protein and higher transport maximum for para-aminohippurate per unit glomerular filtration rate, less histologic evidence of tubulo-interstitial damage, less deposition of complement components C3 and C5b-9, and a lower renal vein total ammonia concentration. Such differences in tubular function could not be accounted for simply on the basis of systemic alkalinization, and differences in tubular injury could not be ascribed to differences in glomerular function. Because nitrogen nucleophiles such as ammonia react with C3 to form a convertase for the alternative complement pathway, and because increased tissue levels of ammonia are associated with increased tubulo-interstitial injury, we propose that augmented intrarenal levels of ammonia are injurious because of activation of the alternative complement pathway. Chemotactic and cytolytic complement components are thereby generated, leading to tubulo-interstitial inflammation. Thus, alkali supplementation reduces chronic tubulo-interstitial disease in the remnant kidney of the rat, and we propose that this results, at least in part, from reduction in cortical ammonia and its interaction with the alternative complement pathway.

show abstract

“…All patients and normal subjects were encouraged to ingest substantial amounts of water 2 h before the study to achieve a good urine flow. 1 h before the study, 10 ,uCi 1251-iothalamate with 0.1 ml epinephrine was injected subcutaneously. One intravenous catheter was used for infusion of NaHCO3; in the opposite arm another intravenous catheter was used to sample blood.…”

Section: Studies In Humansmentioning

confidence: 99%

“…One observation that remains unexplained is the failure of patients with chronic renal failure (CRF) to raise U-B Pco2 with alkalinization of urine (7)(8)(9). This phenomenon is somewhat surprising in that studies of acid excretion in CRF have demonstrated that net acid excretion per nephron is enhanced in renal failure (10,11). In the present study we evaluated the factors controlling the formation of urinary Pco2 in CRF in animals with concentrating defects and(or) acidification defects.…”

Section: Introductionmentioning

confidence: 99%

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

Arruda¹,

Nascimento²,

Mehta³

et al. 1977

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T RA C T Measurement of urine to blood (U-B) carbon dioxide tension (Pco2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary Pco2 is that dissolution of HCO3 in water results in elevation of Pco2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B Pco2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B Pco2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B Pco2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B Pco2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B Pco2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B Pco2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B Pco2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B Pco2. The observed urinary Pco2 was very close to the Pco2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary Pco2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion.

show abstract

The functional adaptation of the diseased kidney. 3. Ammonium excretion.

Cited by 46 publications

References 6 publications

Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat

Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat

Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3.

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

Contact Info

Product

Resources

About