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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Distal urinary acidification abnormalities may arise from transepithelial voltage defects, permeability defects, or proton-secretory defects, but tests to determine the cellular mechanisms underlying secretory abnormalities have not previously been reported. A patient with Sjogren's syndrome and distal renal tubular acidosis due to a secretory defect is described, whose kidney biopsy was examined by fluorescent immunocytochemistry with an antibody to the M(r) 31,000 subunit of the mammalian kidney vacuolar H(+)-ATPase and was compared with normal human kidney. Staining with the anti-H(+)-ATPase antibody in normal human kidney was detected in the brush border microvilli and subvillar invaginations of the proximal tubule and in intercalated cells in the collecting duct. A biopsy sample from the patient was devoid of any anti-H+-ATPase staining in the intercalated cells. Staining was also absent from the proximal tubule brush border microvilli but was present in the subvillar invaginations. Although autoantibodies to normal human kidney membrane proteins were detected in the serum by immunoblot analysis, no immunocytochemical evidence for anti-intercalated cell autoantibodies was observed in the patient's serum. This report demonstrates that the basis for the proton secretory defect in some patients with distal renal tubular acidosis is likely the absence of H(+)-ATPase in the intercalated cells. It also illustrates the potential diagnostic utility of anti-H(+)-ATPase antibodies in the classification of distal renal tubular acidoses.
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PMID:Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosis. 139 25

During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus.
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PMID:Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. 841 May 29

The inner medullary collecting duct (IMCD) is the most distal portion of the nephron and plays an important role in urinary net acid excretion. The terminal or distal two thirds of the IMCD is lined by a single cell type, now termed the IMCD cell, which not only secretes protons, but transports sodium and potassium and responds to many hormones. The IMCD may account for greater than 50% of the excreted acid under control conditions and, during acidosis, absolute acid secretion may increase fivefold. Conversely, during alkalemia, acid secretion by this segment is abolished. Thus, the IMCD responds appropriately to perturbations in systemic acid-base balance. Furthermore, models of renal tubular acidosis have been demonstrated along this nephron segment. Three transporters that are important in acid-base control, the Na+/H+ and the Cl-/HCO3- exchanger and an active proton pump, presumably an H(+)-adenosine phosphatase (ATPase), have been demonstrated in IMCD cells. The former two are situated in the basolateral membrane, while the latter is situated in the apical membrane. Only the proton pump is responsible for actual acid addition to the urine. The intracellular mechanisms that modulate the proton pump are just beginning to be defined. It is likely that acid secretory activity involves exocytic insertion of additional pumps, and is dependent on cell pH changes, which are the primary signal, and on changes in intracellular calcium concentration and calmodulin activity, which are the second messengers.
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PMID:Regulation of acidification in the rat inner medullary collecting duct. 165 87

This article is based on a Basic Science Symposium presented at the 23rd Annual Meeting of the American Society of Nephrology. New information on the segmental transport of ammonium by the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct is integrated into a thesis that NH4+ excretion is controlled by the rate of production, by diffusion of NH3 along gradients established by proton secretion, and by active transport of NH4+. These new concepts are applied to a novel explanation of the pathogenesis of distal renal tubular acidosis.
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PMID:Ammonium transport in the kidney: new physiological concepts and their clinical implications. 193 32

Traditionally, the renal collecting duct has been assigned the dual role of (1) secreting protons derived from dietary metabolism to form luminal NH4+ and titratable acid and (2) generating new HCO3-. This view has recently been challenged. According to current concepts, whole body proton balance is maintained predominantly by the lungs which excrete protons derived from dietary metabolism as the acid anhydride CO2. In the process of excreting CO2, HCO3- is also lost from the body. It is the function of the kidney to generate new HCO3- to replenish this loss. The major site of new HCO3- generation is the proximal tubule rather than the collecting duct. New HCO3- is generated predominantly via the metabolism of organic anions, i.e. alpha-ketoglutarate, citrate, lactate, fatty acids. In the process of generating alpha-ketoglutarate from glutamine, NH4+ is formed. Under normal acid-base conditions, 50% of the NH4+ produced is excreted in the urine, and the remaining 50% is delivered to the renal veins. NH4+ delivered to the renal veins consumes HCO3- during ureagenesis. In the discussion which follows, these new concepts are reviewed and applied to an analysis of the pathophysiology of renal tubular acidosis.
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PMID:The importance of renal ammonia metabolism to whole body acid-base balance: a reanalysis of the pathophysiology of renal tubular acidosis. 228 96

In order to investigate the pathogenesis of medullary nephrocalcinosis, rabbit inner medullary collecting duct cells were grown in media containing different Ca++, PTH and pH levels. It was found that high Ca++ (7.8mM) only reduced growth slightly and that crystalline deposits were found under the cells. This suggests that high Ca++ is not severely toxic to the cells but can lead to deposition of calcium beneath the basement membrane. PTH did not effect cell growth even in the presence of high Ca++ implying that it has an indirect effect on tubular cells in medullary nephrocalcinosis associated with hyperparathyroidism. In renal tubular acidosis these cells are subjected to a persistently high urinary pH and low interstitial pH. Raising the pH reduced the cell growth in normal Ca++ medium whereas lowering the pH increased cell growth in vitro. Our results show that nephrocalcinosis is not due to the direct effect of raised pericellular Ca++ or PTH alone and that persistently alkaline tubular fluid may play a role.
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PMID:An in vitro model of nephrocalcinosis using rabbit inner medullary collecting tubular cell culture. 273 Jun 43

The kidney is responsible for the maintenance of an important sector of the regulation of acid-base balance, i.e., that related to the maintenance of the alkaline reserve of the body and to excretion of fixed acids. In this review, the basic mechanisms of H-ion secretion along the nephron, responsible for bicarbonate reabsorption, titratable acid formation and ammonia excretion, are discussed. The mechanisms responsible for tubule acidification along proximal tubule, thick ascending limb, cortical distal tubule and collecting duct are reviewed, having in mind the function of the apical and basolateral membranes. Finally, the pathophysiological aspects of urinary acidification are discussed, focusing on renal tubular acidosis models (induced by maleate and amphotericin B treatment) and their cellular mechanisms, as well as the role of adrenal steroids in urinary acidification.
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PMID:Role of the kidney in controlling acid-base balance. 307 68

Recent classifications of the several pathophysiologic types of distal renal tubular acidosis (secretory, voltage dependent, and gradient) have been based on the response of acidification parameters to a series of provocative maneuvers in vivo and in vitro. A reduction in the difference in urine and blood CO2 tension during bicarbonate loading (U-B pCO2 gradient), a widely applied parameter, has been employed as an index of reduced distal nephron proton secretion. This study was designed to test the validity of the U-B pCO2 gradient in a variety of experimental models of distal renal tubular acidosis by measuring and comparing disequilibrium pH (a direct technique to detect H+ secretion in situ) with the pCO2 in the papillary collecting duct of the rat in vivo during bicarbonate loading. Chronic amiloride, lithium chloride, and amphotericin-B administration, and the post-obstructed kidney models were employed. Amiloride resulted in an acidification defect which did not respond to sulfate infusion (urine pH = 6.15 +/- 0.08), and was associated with an obliteration of the acid disequilibrium pH (-0.26 +/- 0.05- -0.08 +/- 0.03) and reduction in papillary pCO2 (116.9 +/- 3.2 - 66.9 +/- 2.5 mmHg). The defect induced by lithium administration responded to Na2SO4 (urine pH = 5.21 +/- 0.06) but was similar to amiloride with respect to the observed reduction in disequilibrium pH (-0.04 +/- 0.02) and pCO2 (90.3 +/- 3.0 mmHg). The post-obstructed kidney model was characterized by an abnormally alkaline urine pH unresponsive to sulfate (6.59 +/- 0.06) and a reduction in disequilibrium pH (+0.02 +/- 0.06) and pCO2 (77.6 +/- 3.6 mmHg). Amphotericin-B resulted in a gradient defect as characterized by excretion of an acid urine after infusion of sodium sulfate (5.13 +/- 0.06). Unlike other models, however, amphotericin-B was associated with a significant acid disequilibrium pH (-0.11 +/- 0.05) and an appropriately elevated urine pCO2 (119.8 +/- 6.4 mmHg) which did not differ from the respective values in control rats. Thus, these findings support the use of the U-B pCO2 as a reliable means of demonstrating impaired distal nephron proton secretion in secretory and voltage-dependent forms of distal renal tubular acidosis (RTA) and supports the view that proton secretion is not impaired in gradient forms of distal RTA.
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PMID:Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis. 392 66

Ammonium is the most important component of renal acid excretion. A reduced rate of ammonium excretion is the common feature of the group of diseases called distal renal tubular acidosis. We have presented an alternative approach to patients with distal acidification defects based upon the pathophysiology of these disorders. Accordingly, the purpose of this review is to describe a revised classification based on our current understanding of collecting duct hydrogen ion secretion and ammonium addition to the lumen of the distal nephron. We have subdivided these defects into four groups: disorders of the collecting duct proton pump (pump defects); failure to generate and/or maintain an appropriate electrical gradient to favor hydrogen ion secretion (voltage defects); back-leak of hydrogen ions across an abnormally permeable collecting duct membrane (gradient defects), and diminished availability of NH3 in this nephron segment (NH3 defects). These four subtypes can be identified by measuring the urine pH and PCO2 under appropriate circumstances and evaluating the renal excretion of ammonium and potassium.
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PMID:Distal renal tubular acidosis syndromes: a pathophysiological approach. 397 76

In this review, the distal nephron is considered to be that portion of the renal tubule commencing with the thick ascending limb of the loop of Henle and ending with the papillary collecting duct. The collecting duct, including its subdivisions in the cortex and medulla, originates from a different embryologic anlage than more proximal nephron segments, which may explain its morphologic and functional dissimilarities from the thick ascending limb and the distal convoluted tubule. This review summarizes selected aspects of the physiology of the distal nephron, with particular emphasis on the physiology of distal nephron transport of sodium, potassium, chloride and hydrogen ion. The pathophysiologic features of the following disorders of distal nephron function are reviewed: (1) pseudohypoaldosteronism, a heterogenous group of disorders in which the signs and symptoms are suggestive of aldosterone deficiency, but in which aldosterone levels are supernormal and administration of exogenous mineralocorticoid is not ameliorative; (2) pseudohyperaldosteronism (Liddle syndrome), a familial disorder in which the clinical manifestations closely resemble those resulting from an aldosterone-producing adenoma of the adrenal gland (primary aldosteronism), but in which the measured rate of aldosterone secretion and excretion is greatly subnormal; (3) Bartter syndrome and related syndromes of renal potassium wasting; (4) type 1 renal tubular acidosis (classic, distal); (5) type 4 renal tubular acidosis (hyperkalemic). Reference citations are generally to articles reporting recent advances in these areas and to review articles that contain comprehensive bibliographies.
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PMID:Disorders of distal nephron function. 627 92


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