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)

The effect of uranyl nitrate-induced renal failure on the pharmacokinetics of the levo-isomer of propranolol in rats was investigated. The serum clearance of an i.v. dose of propranolol (1.5 mg/kg) in normal animals approached hepatic blood flow, suggesting that the systemic clearance of the drug is rate-limited by blood flow to the liver. Extensive first-pass metabolism was observed after oral administration of l-propranolol was only 7%. Renal failure had no apparent effect on the distribution and elimination of i.v. administered l-propranolol. In contrast, the area under the serum drug concentration time curve after oral administration was increased from 6.95 to 19.3 micrograms X min/ml, which corresponded to a 2.5-fold increase in the systemic availability of l-propranolol (from 7 to 18%). The gastrointestinal absorption of l-propranolol, as assessed by comparing the urinary recovery of radioactivity after i.v. and oral administration of l-[3H]propranolol, was complete in normal animals. Hence, an increase in the extent of absorption of l-propranolol in renal failure cannot be offered as a cause of increased systemic availability. Neither the in vitro nor the in vivo serum protein binding of l-propranolol differed between renal failure and control animals. The intrinsic metabolic clearance of unbound l-propranolol in renal failure rats is estimated to be about 60% lower than that in control rats. These results suggest that the previously reported increase in propranolol serum concentration after oral administration of the drug to uremic patients is due to decreased presystemic biotransformation of the drug.
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PMID:Effect of experimental renal failure on the disposition kinetics of l-propranolol in rats. 663 14

Lipids of the blood serum were studied in 29 patients with untreated nephrotic syndrome (NS) and in 28 patients treated with corticosteroids or nonsteroid drugs. None of the patients had evidence of renal failure, either acute or chronic. The patients with untreated NS showed massive proteinuria, marked hypoproteinemia, considerable hypertriglyceridemia and hypercholesterolemia. Serum high-density lipoprotein cholesterol (HDL cholesterol) concentrations were lower in these patients than in the control group, including 35 normal subjects, and correlated with the total serum protein (r = 0.46, p less than 0.05) and serum albumin (r = 0.46, p less than 0.05). An inverse correlation was observed between HDL cholesterol and serum triglyceride levels (r = -0.58, p less than 0.01). In the treated patients the laboratory indices of NS were less pronounced. HDL cholesterol levels were within normal limits in 14 patients with NS treated mostly with nonsteroid drugs, while in the patients receiving the corticosteroids (14 subjects) they were significantly higher than in the control group.
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PMID:High-density lipoprotein cholesterol in patients with untreated and treated nephrotic syndrome. 671 5

1. Thirty patients with acute renal failure who were unable to eat adequately were evaluated while they received parenteral nutrition with glucose alone (n = 7), glucose and 21 g/day essential amino acids (EAA, n = 11) or glucose, 21 g/day essential and 21 g/day nonessential amino acids (ENAA, n = 12). Energy intake did not differ with the three treatments. Patients were studied in a prospective double blind fashion. 2. Thirteen patients recovered renal function and 11 survived to leave the hospital. Those in whom renal failure was attributed to hypotension and/or sepsis had a poorer recovery of renal function (17%) and survival (17%). Recovery of renal function and survival was greater in patients on the medical service as compared to the surgical service and in those who received more energy. Recovery of renal function was worse in those treated with dialysis. There were no differences in recovery of renal function of survival among the three treatment groups. 3. Many patients were markedly catabolic as indicated by nitrogen balances, urea in nitrogen appearance rates (UNA), serum protein concentrations, and plasma amino acid levels. There was no correlation between the degree of catabolism and recovery of renal function or survival. Mean UNA in individual patients also correlated with body weight. Among the three groups, however, UNA was significantly less with the group receiving EAA as compared to ENAA. 4. Serum protein concentrations were lower than normal in all treatment groups. Serum albumin fell significantly during the treatment in the more catabolic patients. Plasma amino acid levels tended to fall in all three groups and concentrations at the end of the treatment were frequently lower than normal. 5. These data suggest that acute renal failure patients who are unable to eat adequately are often hypercatabolic and have a high mortality, particularly if hypotension or sepsis is the cause of renal failure. The improved survival in those with higher energy intakes, the high rate of net protein breakdown, the low serum protein levels and the reduced plasma concentrations of both essential and nonessential amino acids suggest that greater quantities of energy and both essential and nonessential amino acids may be beneficial to such patients.
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PMID:Clinical and metabolic responses to parenteral nutrition in acute renal failure. A controlled double-blind study. 678 9

A prospective nutritional evaluation of 84 unselected patients admitted to a multidisciplinary ICU was performed using anthropometric measurements, creatinine height index (CHI), and serum protein assays. All values tested were significantly lower than those of 40 healthy controls. A matrix of correlation coefficients showed many similarities among the variables studied. Fatal outcome and poor prognosis indices, such as sepsis and renal failure, were analyzed separately. Anthropometric measurements and CHI were not different in the separate groups. Albumin (Alb) and transferrin (Tr) were not different in patients with or without sepsis. Retinol binding prealbumin was significantly higher in patients with renal failure. Thyroxin-binding prealbumin (TBPA) was significantly lower in all the groups. We emphasize the interest of this rapid turnover protein in evaluating nutritional status. We suggest: (1) a systematic nutritional assessment, and (2) an aggressive nutritional support in the ICU patient.
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PMID:Nutritional status in intensive care patients: evaluation in 84 unselected patients. 682 85

The acylureidopenicillins which have been in man are azlocillin, mezlocillin, piperacillin, and furazlocillin (Bay k 4999). They exhibit dose dependent pharmacokinetics and accordingly upon increasing the doses have serum levels which are higher than the multiple of the dose, longer serum half-life (t1/2), and lower clearances (total serum clearance, renal clearance, and non-renal clearance). With doses of 1-2 g, t1/2 very between 0.7-1.1 h, and with 5.0 g 1.2-1.8 g. The elimination phase distribution volume corresponds to 10-30% of the body weight. The agents are excreted mainly through the kidneys. Referenced to the antibacterial activity of unchanged drugs, 50-80% of intravenous doses are eliminated in the urine. Only 25-35% of the dose of furazlocillin is excreted unchanged in the urine. The t1/2 is increased in reduced renal function, but mezlocillin is relatively little influenced by renal failure. With identical dose sizes, azlocillin appears to be subject to dose dependent pharmacokinetics to a higher degree than mezlocillin and piperacillin. Higher serum levels are also reached by azlocillin and the t1/2 of this agent is increased more in reduced renal failure than is the case for mezlocillin. The biliary levels of the acylureidopenicillins are high. A considerable biliary excretion occurs in reduced hepatic parenchymal function. The serum protein binding of these compounds decreases with higher concentrations varying between some 30% for 200 micrograms/ml and 50% for 2 micrograms/ml of azlocillin and mezlocillin, a mean of 16% for piperacillin in concentrations ranging from 20-300 micrograms/ml, and an average of 60% for furazlocillin. The acylureidopenicillins penetrate into tissues, cerebrospinal fluid and foetuses to produce therapeutic levels. The levels are rather low in bone tissue.
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PMID:Overview of acylureidopenicillin pharmacokinetics. 703 64

Since wasting and malnutrition are common problems in patients with renal failure, it is important to develop techniques for the longitudinal assessment of nutritional status. This paper reviews available methods for assessing the nutritional status; their possible limitations when applied to uremic patients are discussed. If carefully done, dietary intake can be estimated by recall interviews augmented with dietary diaries. Also, in a stable patient with chronic renal failure, the serum urea nitrogen (N)/creatinine ratio and the rate of urea N appearance reflect dietary protein intake. A comparison of N intake and urea N appearance will give an estimate of N balance. Anthropometric parameters such as the relationship between height and weight, thickness of subcutaneous skinfolds, and midarm muscle circumference are simple methods for evaluating body composition. Other methods for assessing body composition, such as densitometry and total body potassium, may not be readily applicable in patients with renal failure. More traditional biochemical estimates of nutritional status such as serum protein, albumin, transferrin, and selected serum complement determinations show that abnormalities are common among uremic patients. Certain anthropometric and biochemical measurements of nutritional status are abnormal in chronically uremic patients who appear to be particularly robust; thus, factors other than altered nutritional intake may lead to abnormal parameters in such patients. Serial monitoring of selected nutritional parameters in the same individual may improve the sensitivity of these measurements to detect changes. Standards for measuring nutritional status are needed for patients with renal failure so that realistic goals can be established optimal body nutriture.
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PMID:Methods for assessing nutritional status of patients with renal failure. 739 78

The experience with chronic renal failure in two institutions, a tertiary care referral hospital with a high prevalence of diabetes mellitus and a Veterans Administration Hospital, was utilized to formulate guidelines for the nutritional assessment and therapy of chronic renal failure. For optimal nutritional support of patients with renal failure, it is important to characterize objectively nutritional deficiencies. Thus, dietary history, anthropometric measurements (weight/height ratio, arm muscle circumference, and triceps skinfold), and serum protein measurements (total protein, albumin, and transferrin, in particular) provide valuable data concerning the nutritional status of the patient. The serum urea nitrogen to serum creatinine ratio and urea nitrogen appearance are useful for selecting optimal protein intake. The serum urea nitrogen/creatinine ratio must be interpreted with respect to the factors which influence it; i.e., the urea clearance and the urea nitrogen appearance. The goal of nutritional therapy is the preservation of body cell mass and function, fluid, electrolyte, and acid-base homeostasis, mineral balances, and with early use of dialysis, the avoidance of uremic toxicity. Nutritional therapy, especially in patients with superimposed illnesses and associated anorexia, may be enhanced by the use of formula feedings, tube feedings, and, if necessary, total parenteral nutrition.
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PMID:Nutritional assessment and treatment of chronic renal failure. 739 79

The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7 +/- 3.0 h (mean +/- SD) and it was not significantly prolonged in patients with renal failure (18.1 +/- 5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6 +/- 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
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PMID:Pharmacokinetics of naproxen in subjects with normal and impaired renal function. 743 46

The present study was directed towards determining serum protein abnormalities, with emphasis on protein deficits in patients on short- and long-term hemodialysis. Serum protein profiles of healthy controls and chronic and end-stage renal failure patients on hemodialysis were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A total of 104 distinct peptide bands in the molecular weight range of 23 kDa to 300 kDa were encountered for both healthy and patient populations. The SPSS/PC+ discriminant analysis employing group mean statistics revealed significant protein deficits in the patient population. As many as 72 (69.23%) of the 104 individual peptide bands had lower mean scores for the patients as compared to the healthy subjects. In all, 21 (29.2%) of these peptide bands belonged to the high molecular weight range of 185 kDa to 300 kDa while 13 (18.1%) were located in the low molecular weight range of 23 kDa to 36 kDa. To show that patients and healthy controls can be categorized into their respective groups on the basis of their serum protein profiles, a 100% correct classification was established by group membership prediction analysis. Furthermore, using minimization of Wilk's lambda as the criterion for variable selection, it was found that the 285 kDa, 265 kDa, 250 kDa, 155 kDa, 125 kDa, 110 kDa, 32 kDa, 27.5 kDa, 26 kDa and 23.5 kDa serum peptide bands were the most important in classifying an individual as healthy or diseased.
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PMID:Evaluation of serum peptide banding patterns of patients on hemodialysis therapy by discriminant analysis. 759 May 16

To clarify the natural history of IgA nephropathy and to determine important factors in the progressive loss of renal function in affected patients, 121 patients with IgA nephropathy were followed for a median of 92 months. The cumulative probability of not progressing to end-stage renal failure (that is, of renal survival) was 0.87 at 15 years after the onset of 1st symptoms and 0.86 at 10 years after presentation and biopsy. Eight percent of patients progressed to end-stage renal failure, and 12% had a greater than 20% decline in renal function. A complete remission of disease activity was seen in 12% of patients, and the remaining 68% maintained stable renal function. When the final serum creatinine was expressed as a percentage of the initial serum creatinine for each patient and compared with all other variables, a number of factors were found to affect renal outcome. Of the presenting features, increased age, family history of nephritis, longer duration of symptoms, and presence of either nephrotic-range proteinuria or hypertension were all associated, by univariate analysis, with an adverse outcome, while a history of recurrent macroscopic hematuria and infection-associated exacerbations of disease activity were associated with a favorable outcome. Multivariate analysis showed that nephrotic-range proteinuria had an independent adverse effect. Of the initial laboratory findings, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, raised beta globulins on serum protein electrophoresis, and serum C4 concentrations were all associated with an adverse outcome, while the severity of initial hematuria and pyuria were associated with a favorable outcome. Renal biopsy findings associated with an adverse outcome by univariate analysis include, on light microscopy, the percentage of glomeruli with global sclerosis or segmental sclerosis or adhesions, the degrees of tubular atrophy or interstitial fibrosis, interstitial inflammation and blood-vessel thickening, and, on immunofluorescence, the intensity of IgA deposition. Multivariate analysis showed independent adverse effects on renal outcome of global glomerulosclerosis, segmental glomerulosclerosis or adhesions, and a combined mesangial and capillary wall deposition of IgM. Features at final assessment or during follow-up associated with an adverse outcome include, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, reduced serum IgG and IGM concentrations, reduced final IgA expressed as a percentage of the initial IgA concentration, transient decreases of creatinine clearance during follow-up of > 10% or > 20%, and persistence or development of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. 815 67


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