Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previously nephrectomized patient with a well functioning renal allograft, acute renal failure with massive polyuria and hypertension developed. Relief of a periureteric obstruction resulted in rapid correction of all three. Pathogenesis of hypotonic polyuria is thought to be a defect in the collecting duct permeability to water, stimulating nephrogenic diabetes insipidus. Normal urinary dilution and acidification suggest intact function of the ascending loop of Henle and distal convoluted tubules. The quick reversal of polyuria and renal failure after obtaining relief of the obstruction suggest that both the decrease in the glomerular filtration rate and tubular dysfunctions are due to functional changes in the nephron rather than to organic damage, a possibility also borne out by the findings in a renal biopsy specimen showing normal glomeruli and intact tubular epithelial cells. Ureteric obstruction should be considered in any patient with renal failure and polyuria; it may be a correctable cause of hypertension.
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PMID:Obstructive polyuric renal failure following renal transplantation. 79 85

Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure.
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PMID:Diuretic agents. Mechanisms of action and clinical uses. 126 95

The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 +/- 4.7%) than in normal animals (14.1 +/- 2.8%, p < 0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 +/- 7.4%) and fractional potassium excretion (136.3 +/- 32.7%) were higher than in normal animals (20.4 +/- 3.8%, p < 0.05, and 43.6 +/- 9.0%, p < 0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+3.7 +/- 0.4 vs. 3.9 +/- 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (Posm; 0.9 +/- 0.4 x 10(-5) cm/s.atm) and diffusional permeability (34.7 +/- 6.6 x 10(-5) cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 +/- 0.7 x 10(-5) cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low P(o)sm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin.
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PMID:Renal involvement in leptospirosis: a pathophysiologic study. 143 48

Inner medullary collecting duct function in ischemic acute renal failure: The purpose of this study was to determine the role of the medullary collecting duct in the increased urine sodium concentration, decreased urine osmolality, and altered potassium excretion with hyperkalemia which are characteristic of ischemic acute renal failure. Microcatheterization of the inner medullary collecting duct (0.1 to 5 mm from papillary tip) was carried out in rats 24 h after bilateral renal artery clamping for 45 min (n = 8) or sham-operated (n = 8). In ischemic acute renal failure (ARF), tubular fluid osmolality did not increase significantly along the inner medullary collecting duct (IMCD). Tubular fluid sodium concentration was similar to controls at the beginning of the IMCD but was significantly higher at the papillary tip. Tubular fluid to plasma potassium concentration ratio (TF/PK) increased to a greater extent along the IMCD in ischemic ARF than in controls. During acute KCl loading in two additional groups, tubular fluid potassium concentration and TF/PK were much lower at the beginning of the IMCD in ischemic ARF than in controls but increased similarly along the IMCD. In ischemic ARF, with or without KCl loading, renal tissue electrolytes showed reduced potassium concentration in the outer medullary region. The results indicate that impaired IMCD function contributes significantly to the increase in urine sodium concentration and the decrease in urine osmolality which are characteristic of ischemic acute renal failure. In ischemic ARF with mild hyperkalemia, an adaptive increase in K secretion occurred in the IMCD. Severe hyperkalemia and decreased potassium excretion during acute potassium loading in ischemic ARF were determined in more proximal nephron segments and were associated with decreased outer medullary tissue potassium, presumably due to tubular necrosis. Decreased outer medullary tissue potassium could contribute to hyperkalemia by diminishing K secretion in the pars rectae and descending limbs or in the cortical and outer medullary collecting ducts.
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PMID:Inner medullary collecting duct function in ischemic acute renal failure. 340 4

Cis-dichlorodiammine platinum (II), or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. The vulnerability of the kidney to cisplatin is almost certainly related to its primary role in the excretion of cisplatin. Cisplatin enters renal cells by a process that depends on normal oxygen utilization and is specifically inhibited by organic bases. Greater localization of platinum to the S3 segment of the proximal tubules suggests that the vulnerability of this segment may depend on its specific uptake of the drug. The majority of intracellular platinum is bound to macromolecules, including protein and DNA, yet a significant portion of cell platinum is biotransformed to a nonmutagenic and possibly nontoxic compound. Polyuria and hypomagnesemia, which are commonly associated with cisplatin nephrotoxicity, may be due to defects in deep nephron or collecting duct fluid and solute transport. Low single nephron glomerular filtration rates (SNGFR) during early cisplatinum-induced acute renal failure is accompanied by reduced renal blood flow and transglomerular hydrostatic pressure without elevated intratubular hydrostatic pressure, suggesting preglomerular vasoconstriction as an important determinant of renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin nephrotoxicity. 353 59

Acetazolamide, furosemide, chlorothiazide and amiloride are pharmacologic agents that act primarily in the proximal tubule, loop of Henle, early distal tubule and late distal tubule and collecting duct, respectively. These diuretic agents were used to evaluate the functional integrity of discrete segments of the nephron in the neonatal rat following treatment with a known nephrotoxicant. Six-day old rats were treated s.c. with the proximal tubule toxicant mercuric chloride (1 or 3.2 mg/kg) or saline. Twenty-four hours later, when evidence of mercury nephrotoxicity is detectable, creatinine clearance and the fractional excretion of water and various components of the filtrate were determined using a 2-hr clearance period immediately after injection of a diuretic. The effects of mercury (3.2 mg/kg) were consistent with its ability to cause acute renal failure and proximal tubular necrosis and also indicated an apparent disruption of the cycling of urea in the nephron. A decrease in the fractional excretion of water, combined sodium and potassium and total osmotic solutes indicated that the diuretic response to acetazolamide was markedly attenuated in the mercuric chloride-treated pups whereas the responses to furosemide, chlorothiazide and amiloride were not altered by mercury treatment. Results from this study illustrate the specificity of these diuretics as pharmacologic probes of mercuric chloride induced renal dysfunction and, therefore, support their usefulness as tools in the investigation of renal developmental toxicity.
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PMID:Pharmacologic probing of mercuric chloride-induced renal dysfunction in the neonatal rat. 361 27

Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated with its use including chronic and acute renal failure, renal magnesium wasting, and polyuria. We have investigated polyuria in groups of rats treated with cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks to determine possible mechanisms of this impairment. After cisplatin administration, glomerular filtration rate was reduced and significant increases in sodium and water loss were also seen. These changes were associated with decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were removed from these animals and were stimulated with graded doses of vasopressin. Cells from cisplatin-treated rats showed an impaired response in cAMP generation to vasopressin stimulation as compared to cells from normal animals. To determine more precisely the site of impairment, the adenylate cyclase complex of the IMCD cells was further studied with forskolin and NaF. Forskolin was used to probe the catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide regulatory protein (G protein). In response to forskolin, cells from cisplatin-treated rats and normal rats responded similarly in generating cAMP. However, following NaF, the cAMP response was blunted in the cells from the cisplatin rats. These results suggested that the catalytic unit was not injured by cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the present study suggests that the polyuria seen following cisplatin administration is associated with an end-organ resistance to vasopressin manifested by reduced cAMP generation, secondary in part or whole to a defect at the level of the G protein.
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PMID:Mechanism of polyuria after cisplatin therapy. 830 21

Therapy with foscarnet is associated with acute renal failure. Prior studies have emphasized foscarnet's proximal tubular toxicity, but there have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However, foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been previously investigated. We studied foscarnet's modulation of transport in the toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inhibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1.0 mIU of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea flux. Foscarnet also increased water flow induced by 1.0 to 10 microM forskolin. In tissues pretreated with 10 microM naproxen, foscarnet did not alter water flow induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per ml at a site proximal to that of the generation of cyclic AMP and inhibits urea flux induced by a maximal dose of ADH at a separate site. In humans, foscarnet nephrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closely monitored for disorders of urinary concentration.
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PMID:Foscarnet alters antidiuretic hormone-mediated transport. 854 Jul 7

This study was designed to compare the renal effects of atrial (A-type) natriuretic peptide (ANP) on control (saline-injected) rats and rats with non-oliguric acute renal failure induced by cisplatin. The results obtained here are summarized as follows: (1) In the metabolic cage study, cisplatin-treated rats showed increases in blood urea nitrogen and serum creatinine while creatinine clearance decreased to the lowest levels on day 4. A transient increase in urinary protein was observed at day 4. (2) ANP infusion significantly increased urine flow rate (UFR), creatinine clearance (CCr), fractional excretion rates of sodium (FENa) and chloride (FECl), and urinary phosphorus and magnesium (Mg) excretions in a dose-dependent manner without affecting renal plasma flow and fractional excretion rates of potassium and urea in cisplatin-treated rats. (3) Renal effects of ANP on UFR, CCr, FENa, FECl and excretion of Mg were more pronounced in cisplatin-treated rats compared to control rats although markedly blunted responses to ANP have been reported in nephrotic patients and nephrotic animals induced by adriamycin and aminonucleoside. (4) Histological examination showed extensive necrosis of the S3 segment of the proximal tubule located in the outer stripe of the outer medulla with minimal glomerular abnormalities in the kidney of cisplatin-treated rats. In conclusion, the main mechanism of the increased renal responses to ANP is considered to be due to an increased delivery of sodium, fluid and ANP itself to the inner medullary collecting duct which is the major renal site of action of ANP under the condition of acute proximal tubular necrosis by cisplatin.
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PMID:Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin. 872 36

Cytodiagnostic urinalysis was tested to determine its utility in the differential diagnosis of acute renal failure (ARF). Fifty-one patients with acute renal failure were included and evaluated clinically with regard to the etiology of the renal failure, whether underlying chronic renal failure was present, and if dialysis was required. Urine specimens were macroscopically examined and subjected to a multiparameter reagent-strip analysis. Papanicolaou stain was done on cytocentrifuge preparations and the number of blood cells, renal cells, and casts examined in a standardized fashion. The results showed that the 34 patients with acute tubular necrosis (ATN) of either ischemic or toxic origin had a higher number of collecting duct cells, and a higher total number of casts than the 17 non-ATN patients. Twelve patients requiring dialysis had a higher number of different types of casts (granular, waxy, leukocytic, broad casts) as well as more renal cells (mainly necrotic) than the 39 patients who did not require dialysis. A significant positive correlation was found between the magnitude of rise of serum creatinine and a number of cytodiagnostic parameters. We conclude that cytodiagnostic urinalysis may be valuable in addition to other tests in the evaluation of patients with acute renal failure.
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PMID:Cytodiagnostic urinalysis is very useful in the differential diagnosis of acute renal failure and can predict the severity. 877 Dec 45


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