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)

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. In order to investigate the renal pathophysiology induced by amphotericin B, these diuretic agents were used as probes of discrete segments of the nephron in the neonatal rat. Six-day-old rats were treated with amphotericin B (20 mg/kg, sc) or the vehicle. Twenty-four hours later, when evidence of amphotericin B-induced renal pathophysiology is detectable, the responses to the diuretic agents were assessed in a 2-hr clearance test, during which creatinine clearance (CCr) and the fractional excretion (FE) of water and various components of the filtrate were determined. Amphotericin B induced alterations in basal function including azotemia, hypostenuria, increases FE water and electrolytes, and a decreased FE urea (although CCr was normal). The diuretic responses to furosemide, chlorothiazide, and amiloride were not altered, indicating that the functional viability of the respective tubular segments was not affected by amphotericin B treatment. Although the maximal response to acetazolamide also remained unchanged in amphotericin B-treated pups, there was an attenuation in the half-maximal response, reflecting an apparent shift in the sensitivity to acetazolamide. All of the diuretic agents elicited an increase in urea excretion in amphotericin B-treated pups such that FE urea approached control values. Additionally, the magnitude of this increase was proportional to the magnitude of the increase in water excretion induced by each diuretic agent. These results indicate a disruption of urea recycling in the nephron and support the hypothesis that amphotericin B acts to increase the permeability of the distal tubule to urea. Thus, results from this study demonstrate the usefulness of pharmacologic agents as functional probes in the characterization of specific components of renal pathophysiology.
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PMID:Pharmacologic probing of amphotericin B-induced renal dysfunction in the neonatal rat. 336 16

Nephrotoxicity is the major adverse effect of conventional amphotericin B (AMB/D), often limiting administration of full dosage. The new liposomal amphotericin B seems to be less toxic. The new liposomal amphotericin B seems to be less toxic. In this study, it is proposed that solubilizing the standard AMB/D preparation with 10% lipid emulsion will attenuate nephrotoxicity. Rats were injected with either AMB/D (Fungizone), AMB, AMB/D plus lipid emulsion (AMB/D/LE), or sodium deoxycholate (D). Renal function studies were performed on day 5. To assess a direct tubular toxic effect, isolated rat proximal tubule suspensions and inner medullary collecting duct cells in culture were exposed to AMB/D, AMB, AMB/D/LE, liposomal amphotericin B, and D for 60 min in normoxia. Lactate dehydrogenase (LDH) release was assessed as an index of cell injury. Creatinine clearance (ml/min per 100 g) averaged 0.79 +/- 0.04 in control rats, 0.29 +/- 0.09 in AMB rats (P < 0.001 versus control), 0.38 +/- 0.04 in AMB/D rats, 0.46 +/- 0.05 in D rats, and 0.78 +/- 0.03 in AMB/LE rats. Renal blood flow (ml/min per 100 g) was 3.45 +/- 0.31 in control, 1.29 +/- 0.28 in AMB, 1.42 +/- 0.23 in AMB/D, 3.03 +/- 0.39 in D, and 2.71 +/- 0.21 in AMB/D/LE rats. The fractional excretion of potassium (%) was 27.3 +/- 1.18 in control rats, 61.6 +/- 7.00 in AMB/D rats, 58.4 +/- 15.32 in AMB rats, and 37.9 +/- 2.06 in AMB/D/LE rats. LDH release (%) in proximal tubules incubated with AMB/D and D was 43.6 +/- 3.39 and 58.6 +/- 4.20, respectively. Addition of lipid emulsion decreased LDH release: 21.6 +/- 1.22 for AMB/D/LE and 26.4 +/- 3.03 for deoxycholate plus lipid emulsion. AMB did not demonstrate any toxic effect in proximal tubule suspensions. D was not toxic to inner medullary collecting duct cells at 0.16 mg/ml, whereas D at a higher dose and AMB induced a significant LDH release. Addition of lipid emulsion did not affect the antifungal activity as assessed by the Etest method. In conclusion, an alternative way of administering standard AMB with reduced nephrotoxicity is proposed.
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PMID:Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion. 929 33