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)

To assess the intrinsic effects of treatment with furosemide on free-water excretion in patients with chronic renal failure, two groups of patients with and without replacement of diuretic-induced salt losses have been studied. Furosemide therapy was administered for 1 week during constant sodium intake (100 mEq/day). In neither of the groups did furosemide cause hyponatremia, while it did decrease the urine to plasma osmolality ratio, an effect lasting even when the diuretic effect was exhausted. During water diuresis, furosemide decreased the fractional sodium reabsorption in diluting segments but not the absolute rate of the free-water generation (CH2O). Presumably the expected decrease of CH2O was masked by the increased distal delivery of tubular fluid mainly due to an additional effect of the diuretic on the proximal tubule. The hypotonicity of urine after furosemide treatment may be secondary to the dissipation of medullary hypertonicity, caused by furosemide, in the condition of decreased water permeability of the collecting duct due to uremic disease.
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PMID:Effects of furosemide therapy on free-water excretion in uremic patients. 323 71

Comprehensive one-day renal function tests in 20 patients with a history of analgesic abuse showed varying degrees of chronic renal failure in all. There was no evidence of a selective defect in proximal tubular function, while a defective concentrating mechanism, usually considered necessary for the diagnosis of analgesic-induced renal damage, could be demonstrated in only 16 patients. A urinary acidification defect associated with a concentrating defect was found in nine cases and was thought to reflect specific collecting duct dysfunction. Urinary ammonium excretion was reduced in 13 subjects, owing to a reduced number of functioning nephrons or inadequate acidification, or both. Low citrate excretion was frequently encountered, and this, as well as defective urinary acidification, may play some part in predisposing patients with analgesic nephropathy to intrarenal calcification and progressive renal failure.
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PMID:Renal function in analgesic nephropathy. 578 Apr 28

Alterations in the renal metabolism and/or actions of endothelin-1 (ET-1) may be involved in the pathogenesis and maintenance of essential and renal parenchymal hypertension. ET-1 has the potential to modify a broad range of renal functions involved in controlling systemic blood pressure. First, the kidney clears a large percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute to hypertension occurring in the setting of chronic renal failure. Second, ET-1 potently constricts the renal vasculature resulting in increased fluid retention and possibly contributing to glomerular sclerosis; enhanced renal vascular and glomerular ET-1 production and target cell actions may play a role in essential hypertension or hypertension accompanying chronic renal failure, cyclosporine administration, or erythropoietin therapy. Lastly, ET-1 is also an autocrine inhibitor of collecting duct sodium and water reabsorption; reduced nephron ET-1 production may result in fluid retention in essential hypertension. Determination of the true role that ET-1 plays in the pathogenesis of the varied forms of hypertension awaits the development of safe, potent, and specific endothelin antagonists.
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PMID:Role of intrarenal endothelin in the generation and maintenance of hypertension. 756 83

Endothelin is an important modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine-autocrine factor in the regulation of renal blood flow, glomerular hemodynamics, and sodium and water homeostasis. Recent evidence suggests that circulating endothelin may play an important role in renal regulation in cardiorenal states of endothelin activation. Endothelin is a potent renal vasconstrictor that has dual actions on glomerular filtration rate due to its ability to preferentially constrict efferent arterioles preserving glomerular filtration. Furthermore, endothelin modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, respectively, by mechanisms that are still unclear. In addition, endothelin stimulates the renin-angiotensin-aldosterone system and atrial natriuretic peptide release and inhibits arginine vasopressin-mediated water reabsorption in the inner medullary collecting duct. Recent studies using specific receptor antagonists have demonstrated a pathophysiologic role for endothelin during renal ischemia, cyclosporine-induced toxicity, and chronic renal failure. This review highlights recent research that supports an important role for endothelin as a locally produced vasoactive and natriuretic peptide in the regulation of renal hemodynamic and excretory functions.
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PMID:Physiologic and pathophysiologic roles of endothelin in the kidney. 785 Apr 14

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

Endothelin (ET) is a peptide with profound vasoconstrictive potential. First isolated from porcine endothelial cell supernatant, it is produced also by smooth muscle, epithelial and circulating cells. Besides vasoconstriction, a wide spectrum of biological activities of ET (via activation of membrane receptors) has been described. These include regulation of other hormones and neurotransmitters, cellular growth and proliferation, bronchoconstriction, and, in the kidney, natriuresis and water diuresis. ET exerts its effects mainly in an autocrine and paracrine fashion. A high concentration of ET is found in urine, compared with plasma originating mainly from the kidney itself. In this review we focus on the role of urinary excretion of ET in children. ET excretion was determined under different physiological and pathological conditions. In premature infants and newborns, the daily excretion of ET (corrected for body surface) was higher than in older children; it was constant, and comparable to the values in healthy adults after the age of 2 years. Renal ET excretion correlated positively with urine flow in both healthy and sick children. Conditions with tubular and/or collecting duct cell damage, such as severe hypoxia, hemolytic-uremic syndrome, renal transplantation, diabetes mellitus, chronic renal failure, and contrast media cytotoxicity were characterized by elevated urinary excretion of ET. In conclusion, the renal excretion of ET is influenced by several factors, probably reflecting the intrarenal ET production. ET has a low specificity with regard to renal injury.
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PMID:Renal excretion of endothelin in children. 926 Feb 60

Urinary concentration characteristically decreases in response to a reduction in renal mass in chronic renal failure (CRF). In the present study, we examined whether there are changes in the expression of aquaporins in rats where CRF was induced by 5/6 nephrectomy. Plasma creatinine levels were significantly elevated consistent with significant CRF: 135.7 +/- 15.1 (n = 17, CRF) vs. 33. 9 +/- 1.1 micromol/l (n = 11, sham), P < 0.05. Two weeks after 5/6 nephrectomy, the remnant kidneys were hypertrophied, and total renal mass increased to 65 +/- 3% of sham levels (P < 0.05). Urine production increased markedly from 40 +/- 2 to 111 +/- 3 microliter. min-1. kg-1 in CRF rats (P < 0.05), whereas urine osmolality and solute-free water reabsorption decreased significantly. Quantitative immunoblotting of total kidney membrane fractions revealed a significant decrease in total kidney AQP2 expression in CRF rats to 43 +/- 12% of sham levels (P < 0.05). A similar reduction was observed for AQP1 and AQP3. Furthermore, the increased urine output and decreased urine osmolality persisted in CRF rats despite 7 days treatment with 1-desamino-[8-D-arginine]vasopressin (DDAVP, 0.1 microgram/h sc) compared with untreated sham-operated controls. Also, there was no change in AQP2 expression (which remained at 38 +/- 3% of sham levels, P < 0.05), urine output, or urine osmolality between CRF rats with or without DDAVP treatment. Immunocytochemistry confirmed the decreased AQP2 expression in collecting duct principal cells in CRF rats, with a predominant apical labeling. In conclusion, the results demonstrated that there was a significant vasopressin-resistant downregulation of AQP2 and AQP3 as well as downregulation of AQP1 associated with the polyuria in CRF rats.
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PMID:Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass. 981 30

Chronic renal failure is associated with disturbances in nitric oxide (NO) production. This study was conducted to determine the effect of 5/6 nephrectomy (5/6 Nx) on expression of intrarenal neuronal nitric oxide synthase (nNOS) in the rat. In normal rat kidney, nNOS protein was detected in the macula densa and in the cytoplasm and nuclei of cells of the inner medullary collecting duct by both immunofluorescence and electron microscopy. Western blot analysis revealed that 2 wk after 5/6 Nx, there were significant decreases in nNOS protein expression in renal cortex (sham: 95.42+/-15.60 versus 5/6 Nx: 47.55+/-12.78 arbitrary units, P<0.05, n = 4) and inner medulla (sham: 147.70+/-26.96 versus 5/6 Nx: 36.95+/-17.24 arbitrary units, P<0.005, n = 8). Losartan treatment was used to determine the role of angiotensin II (AngII) AT1 receptors in the inhibition of nNOS expression in 5/6 Nx. Losartan had no effect on the decreased expression of nNOS in the inner medulla, but partially increased nNOS protein expression in the cortex of 5/6 Nx rats. In contrast, in sham rats losartan significantly inhibited nNOS protein expression in the cortex (0.66+/-0.04-fold of sham values, P<0.05, n = 6) and inner medulla (0.74+/-0.12-fold of sham values, P<0.05, n = 6). nNOS mRNA was significantly decreased in cortex and inner medulla from 5/6 Nx rats, and the effects of losartan on nNOS mRNA paralleled those observed on nNOS protein expression. These data indicate that 5/6 Nx downregulates intrarenal nNOS mRNA and protein expression. In normal rats, AngII AT1 receptors exert a tonic stimulatory effect on expression of intrarenal nNOS. These findings suggest that the reduction in intrarenal nNOS expression in 5/6 Nx may play a role in contributing to hypertension and altered tubular transport responses in chronic renal failure.
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PMID:Downregulation of neuronal nitric oxide synthase in the rat remnant kidney. 1020 53

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.
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PMID:Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats. 1049 67

The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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PMID:Physiology and pathophysiology of renal aquaporins. 1132 Apr 86


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