Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In renal failure associated with the nephrotic syndrome, therapeutic strategy is highly dependent upon the cause of the renal failure. Dynamic hippurate scintigraphy was studied in five pediatric patients. Four had nephrotic syndrome, and of these, three had acute renal failure. The fifth patient had end-stage renal failure. Specific alteration in renal hippurate kinetics offers a noninvasive assessment of renal failure in this clinical setting.
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PMID:Differentiation of reversible ischemia from end-stage renal failure in nephrotic children with 131I-hippurate dynamic scintigraphy. 85 22

Furosemide frequently is advocated as a prophylaxis against renal failure in septic and injured patients; this effect is thought to be secondary to an increase in renal blood flow. This postulate was tested within 72 hours of admission in 22 previously healthy patients with acute pancreatitis (two), massive trauma (ten), or severe sepsis (ten). Renal clearances of inulin (GFR), para-amino hippurate (ERPF), sodium (CNA), osmoles (COsm), and free water (CH2O) were measured in milliliters per minute before and after the intravenous infusion of furosemide (0.5 mg. per kilogram of body weight). Renal vein PAH levels (EPAH) in eight patients were used to calculate true renal plasma flow (TRPF), true renal blood flow (TRBF), and renal vascular resistance (RVR). Furosemide caused a significant increase in urine volume, CNa, and COsm; there were no significant changes in GFR, ERPF, RVR, TRBF, and EPAH. These findings also were observed when the patients were subgrouped according to elevated, normal, or low renal plasma flow and elevated renal vascular resistance. No significant changes were seen in EPAH, thus making a redistribution of renal blood flow unlikely. These studies indicate that furosemide has only a diuretic effect and no hemodynamic effect in the kidney; it has the potential of seriously reducing the circulatory volume and causing renal failure in critical patients.
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PMID:Renal hemodynamic response to furosemide in septic and injured patients. 126 63

Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man. 149 65

Organic anions retained in patients with renal failure participate in a substantial way in the metabolic acidosis and thus also the catabolism in renal failure. The basic disorder is the reduced capacity of the transport system of organic ions. Therefore drugs are sought to enhance its activity. Acute investigation of healthy volunteers revealed that 150 mg dipyridamol increased the urinary hippurate excretion, while the serum hippurate concentration declined. In patients with renal failure there is the same tendency, though less marked, and due to the variability of functions of individual patients this trend is insignificant. It is assumed that this hitherto not described action of dipyridamol may be of therapeutic importance when administered to patients with impaired renal function.
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PMID:[The effect of dipyridamole on hippurate excretion in healthy volunteers and in patients with renal insufficiency]. 176 55

Renal failure often complicates endotoxin shock. This might be due to renal hypoperfusion, but endotoxemia could also have additional effects. We studied in anesthetized rats renal plasma flow (RPF), glomerular filtration rate (GFR), and metabolism (ATP, CrP = creatine phosphate, energy charge = [ATP + 0.5 ADP]/[ATP + ADP + AMP], lactate, glucose) during endotoxin shock (Escherichia coli endotoxin, 10 mg/kg for 60 min; n = 10) and "balloon shock" (balloon inflated in vena cava below renal vein to cause comparable decreases in cardiac output and RPF as in endotoxin-treated rats; n = 10). A third group of rats served as controls (n = 10). At t = 0 infusion of endotoxin was started. At t = 90 min, when cardiac output was low and serum lactate was high (indicating shock), GFR and RPF were obtained from plasma disappearance rates (from t = 90 to t = 135 min) of 125I-thalamate and 131I-hippurate, respectively. Experiments ended at t = 135 min. In both shock groups RPF decreased (by ca. - 75% compared with control rats), but filtration fraction only increased (by 72%) in the "balloon shock" rats. In renal biopsies lactate concentration increased more (by 407 vs. 167%) and ATP decreased more (by -63 vs. - 35%) during endotoxin shock than during "balloon shock"; the endotoxin-treated rats also showed a significant decrease in CrP (by - 58%), energy charge (by - 31%), and glucose concentration (by - 34%), and an increase in the number of leukocytes in the glomeruli (by 730%). Renal function and metabolism thus was more affected in this hypodynamic form of endotoxin shock than in "balloon shock." This may be caused by the effects of endotoxin on sticking of leukocytes and renal metabolism.
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PMID:Renal function and metabolism during endotoxemia in rats: role of hypoperfusion. 177 55

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment. 303 69

We have evaluated pH, chloride, calcium and several endogenous aromatic acids as possible causes of the impaired binding of drugs by plasma albumin in renal failure. Changes in pH, chloride and calcium over the range found in renal failure had minimal or no effects on the binding of [14C]salicylate, a model probe which binds to both of the major drug-binding loci of human albumin. Hippurate and indoxyl sulfate were weak inhibitors of binding by normal plasma. Ortho-hydroxy-hippurate was undetectable or minimally elevated, except among patients with elevated plasma salicylate concentration. Although plasma hippurate and indoxyl sulfate concentrations were elevated markedly in patients with renal failure, inhibition of salicylate binding was significantly correlated only with the concentration of indoxyl sulfate. Addition of hippurate and indoxyl sulfate separately and together to normal plasma showed that these ligands could account for only 15% of the impaired binding of salicylate by azotemic plasma. The retained solutes which account for most of this binding defect remain to be identified. This uremic disorder (and perhaps others) is due not to a single chemical but to the additive effect of a family of chemicals.
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PMID:Contributions of hippurate, indoxyl sulfate, and o-hydroxyhippurate to impaired ligand binding by plasma in azotemic humans. 312 Jul 33

In this study, changes of protein binding of nine drugs were evaluated. In addition, theophylline and phenytoin, the two drugs with the most substantial and progressive decrease in protein binding, were further studied by high performance liquid chromatography (HPLC)-fractions of ultrafiltrate of normal and uremic serum, in an attempt to identify substances causing drug protein binding inhibition. There was a marked decline of the protein binding of theophylline, phenytoin and methotrexate (dialyzed patients vs. normals: -20.1, -16.0 and -15.1%, respectively). There was a rise in the protein binding of propranolol, cimetidine and clonidine. The changes observed for diazepam, prazosin and imipramine were less marked. For phenytoin, theophylline, methotrexate and diazepam, protein binding was inversely correlated to the serum creatinine (r = 0.87, 0.80, 0.79 and 0.67, P less than 0.001), and a less pronounced but still significant positive correlation was found for clonidine (r = 0.46, P less than 0.01). Ultrafiltrate, obtained during a hemofiltration session, inhibited protein binding of theophylline and phenytoin in a dose dependent way. After separation of this ultrafiltrate by HPLC, it appeared that for both theophylline and phenytoin at least a part of this inhibitory activity corresponded to the elution zone of hippuric acid. For theophylline two other inhibitory zones were further recognized: one corresponding to the elution zone of NaCl and one in which the responsible substance remained unidentified. Hippuric acid in solution inhibited protein binding of theophylline and phenytoin in a dose dependent way. In conclusion, protein binding of several drugs currently used in renal failure is affected in parallel with renal function, which might affect the therapeutic effectiveness of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug protein binding in chronic renal failure: evaluation of nine drugs. 339 89

We have developed a high-performance liquid chromatography (HPLC) method for assay of hippurate in plasma of patients with renal failure. Hippurate accounts, in part, for the impaired binding of drugs and metabolites to albumin and may cause other disorders in azotemic patients. The method is precise, accurate and reproducible. Among 25 patients with acute and chronic renal failure having serum creatinine in the range of 2.9-43 mg/dl (256-3,801 mumol/l), plasma hippurate ranged from 0.11 to 16.2 mg/dl (6.1-904 mumol/l). Hippurate concentration correlated moderately closely with plasma creatinine, urea and anion gap. Its curvilinear relation to the reciprocal of serum creatinine indicated a proportional decline of GFR and tubular function or the accumulation of inhibitors of the proximal tubular anion secretory pathway. The method should be useful for further studies of abnormal albumin binding as well as other disorders in azotemic patients.
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PMID:Plasma hippurate in renal failure: high-performance liquid chromatography method and clinical application. 369 32

The binding by serum albumin of many drugs and endogenous metabolites is impaired in humans and animals with renal failure. Unknown solute(s) retained in renal failure have been extracted from uremic fluids. When added to normal plasma they induce a similar binding defect. Similar activity can be extracted from normal urine. We have devised a series of extraction and purification techniques that yielded three binding inhibitory ligands from normal human urine in sufficient quantity and of a high degree of purity. Rigorous methods have been applied to determine chemical identity of the ligands. Purification steps consisted of: adsorption at pH 3.0 to polystyrene-divinylbenzene resin (XAD-2); elution from the resin with methanol followed by drying and solution in dilute formic acid; passage through SP-Sephadex to remove cations, especially yellow-brown pigments; adsorption to the anion exchanger QAE-Sephadex, and separation into three zones of inhibitory activity with a formic acid gradient; purification to homogeneity with C-8 or C-18 silica reversed-phase chromatography. Using this isolation procedure, followed by mass spectroscopy and nuclear magnetic resonance spectroscopy, we have shown that the binding inhibitory activity is due not to one ligand, but to a family of aromatic acids. To date hippurate, beta-(m-hydroxyphenyl)-hydracrylate and p-hydroxyphenylacetate have been identified as binding inhibitors. Other active ligands remain to be identified.
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PMID:Isolation and chemical identification of inhibitors of plasma ligand binding. 378 82


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