Disorders of distal nephron function

Sebastián, Anthony; Hulter, Henry N.; Kurtz, Ira; Maher, Terry; Schambelan, Morris

doi:10.1016/0002-9343(82)90822-1

Cited by 24 publications

(11 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In three studies [3,7,8], the metabolic acidosis was thought to be of proximal origin, on the basis of a subnormal bicarbonate threshold [7,8] or a subnormal capacity of HCO3 reabsorption [3]. In the case reported by Brautbar et al [2], the metabolic acidosis, which dis appeared after correction of hyperkalemia by cation ex change resin, was considered to be due to the decline in renal ammonia production as in type IV renal tubular acidosis [10,11], In 2 other cases [5,6], metabolic acido sis and hyperkalemia were attributed to a subnormal aldosterone secretion, secondary to chronic extracellular volume expansion, on the basis that metabolic acidosis and hyperkalemia disappeared after sustained dietary so dium restriction [5], Recent findings, however, suggest that the primary abnormality of this syndrome would be a chloride shunt in the distal nephron which would diminish the lumen-negative transtubular electrical po tential difference and thereby reduce the electrical driving force for K secretion [12], In this event, metabolic acido sis was mainly attributed to a reduction in II secretion in the distal nephron secondary to the chloride shunt [12], The diminution of transtubular potential difference re sulting from the chloride shunt would be responsible for the subnormal rate of H secretion in the distal nephron [12,13],…”

Section: Introductionmentioning

confidence: 99%

Pseudohypoaldosteronism Type II: Proximal Renal Tubular Acidosis and dDAVP-Sensitive Renal Hyperkalemia

et al. 1986

View full text Add to dashboard Cite

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3–6.9 mmol/l), metabolic acidosis (arterial blood pH 7.27, total CO₂ 17 mmol/l), arterial hypertension, undetectable plasma renin activity ( < 0.10 ng/ml/h), high plasma aldosterone level (32–100 ng/dl), and normal glomerular filtration rate (131 ml/min/1.73 m²). During the hyperkalemic period, urine was highly acidic (pH 4.6–5.0), urinary NH₄ excretion (10–13 μEq/min) and urinary net acid excretion (19–24 μEq/min) were not supernormal as expected from a chronic acid load. During NaHCO₃ infusion, the maximal tubular HCO₃ reabsorption was markedly diminished (19.8 mmol/l glomerular filtrate), and the fractional excretion of HCO₃ (FE HCO₃) when plasma HCO₃ was normalized was 20%. Urine minus blood PCO₂ increased normally during NaHCO₃ infusion (31 mm Hg), and the urinary pH remained maximally low ( < 5.3) when the buffer urinary excretion sharply increased after NH₄C1 load. When serum K was returned toward normal limits, metabolic acidosis disappeared, urinary NH₄ excretion rose normally after short NH₄C1 loading while the urinary pH remained maximally low (4.9–5.2), the maximal tubular HCO₃ reabsorption returned to normal values (24.8 mmol/l glomerular filtrate), and FE HCO₃ at normal plasma HCO₃ was 1 %. Nasal insufflation of l-desamino-8-D-Arginine Vasopressine (dDAVP) resulted in an acute normalization of the renal handling of K and in an increase in net urinary acid excretion. We conclude that: (1) the effect of dDAVP on renal handling of K may be explained by the reversal of the distal chloride shunt and/or an increase in luminal membrane conductance to K; (2) the distal acidification seems to be normal which in the event of distal chloride shunt impairing distal hydrogen secretion might be explained by the presence of systemic acidosis which is a potent stimulus of hydrogen secretion, and (3) metabolic acidosis in the steady state was accounted for by the diminution of bicarbonate reabsorption and ammonia production in the proximal tubule secondary to chronic hyperkalemia.

show abstract

Section: Introductionmentioning

confidence: 99%

Pseudohypoaldosteronism Type II: Proximal Renal Tubular Acidosis and dDAVP-Sensitive Renal Hyperkalemia

et al. 1986

View full text Add to dashboard Cite

show abstract

“…Notably, however, urine pH declined less in relation to blood pH and bicarbonate concentration in the CA-II-immunized mice. Accordingly, the CA-II-immunized mice exhibited a urinary acidification defect when compared with the control mice [15, 16]. The pathophysiology of the acidification abnormality in these mice corresponded to a subset of human RTA patients with an ‘incomplete’ type of (distal) RTA: lack of metabolic acidosis at baseline and an impaired urinary acid excretion in response to an acid load, as originally described by Wrong and Davies [17].…”

Section: Discussionmentioning

confidence: 90%

Induction of Anti-Carbonic-Anhydrase-II Antibody Causes Renal Tubular Acidosis in a Mouse Model of Sjögren’s Syndrome

Takemoto¹,

Katori²,

Sawa³

et al. 2007

Nephron Physiol

View full text Add to dashboard Cite

Background/Aim: We recently reported that renal tubular acidosis (RTA) in Sjögren’s syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. Methods: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. Results: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. Conclusion: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

show abstract

“…Such a view is based on the observation that urine pH in dogs with aldosterone deficiency is low during periods of reduced buffer excretion but increases above that observed in mineralocorticoid replete dogs when buffer excretion is increased (1,4,22). Nevertheless, a segmental analysis of acidification in selective aldosterone deficiency has not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

“…A "rate" defect, therefore, would be associated with preservation of the ability to achieve a normal minimal urine pH with systemic acidosis but low rates of proton secretion would be observed at higher luminal pH (35). Such appears to be the case in aldosterone deficiency as observed clinically (22,35) and in experimental animal models (1,4). Since deficiency of aldosterone should slow the rate of proton secretion, it follows that the urinary Pco2 during an alkaline diuresis (14) might be reduced.…”

Section: Effects Ofcmamentioning

confidence: 94%

Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.

DuBose

Caflisch²

1988

J. Clin. Invest.

View full text Add to dashboard Cite

Mineralocorticoid plays a role in urinary acidification and acid-base balance, but the response of the inner medulla to aldosterone has not been elucidated. A model of selective aldosterone deficiency (SAD) with hyperkalemia and hyperchloremic metabolic acidosis was employed to assess segmental acidification by measuring in situ pH, titratable acidity (TA) and total ammonia (Am). Hydrogen ion secretion was also examined as a function of the increment in in situ Pco2 in the collecting duct during bicarbonate loading. SAD rats were compared to ADX controls that received adrenalectomy and chronic replacement of gluco-and mineralocorticoid and to rats with chronic metabolic acidosis induced by oral NH4Cl (CMA). Both fractional and absolute delivery of Am to the loop of Henle was lower in SAD vs. CMA rats (1.34 to 3.63 mM, P < 0.01). Delivery of Am to the base and tip collecting duct (BCD and TCD) was also markedly lower in SAD (1.50 vs. 0.52 and 1.77 vs. 0.47 mM, respectively, P < 0.01). Net addition of Am and net acid between BCD and TCD, observed in CMA rats, was not observed in SAD despite equivalent degrees of systemic metabolic acidosis. Similarly, the concentration gradient favoring transfer of NH3 between loop of Henle and CD was reduced in SAD. During bicarbonate loading the increment in Pco2 at BCD, TCD and in final urine was significantly lower in SAD rats than in adrenal intact bicarbonate-loaded rats. Therefore, the acidification defect in this model of SAD appears to be a result of a decrease in ammonia production and delivery to the loop of Henle, impaired transfer from loop to collecting duct and reduction in the rate of H+ secretion by the collecting duct.

show abstract

Disorders of distal nephron function

Cited by 24 publications

References 62 publications

Pseudohypoaldosteronism Type II: Proximal Renal Tubular Acidosis and dDAVP-Sensitive Renal Hyperkalemia

Pseudohypoaldosteronism Type II: Proximal Renal Tubular Acidosis and dDAVP-Sensitive Renal Hyperkalemia

Induction of Anti-Carbonic-Anhydrase-II Antibody Causes Renal Tubular Acidosis in a Mouse Model of Sjögren’s Syndrome

Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.

Contact Info

Product

Resources

About