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Sample records for renal glucose clearance

  1. Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure.

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    Maeda, M; Otsuki, M; Okano, K; Yamasaki, T; Baba, S

    1981-01-01

    Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.

  2. Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats

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    MS. Melis

    Full Text Available Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h, according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin and p-aminohipuric acid clearance (C PAH were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+, fractional potassium excretion (FeK+, urinary flow as percent of glomerular filtration rate (V/GFR and glucose clearance (C G when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

  3. Peritoneal clearance of homocysteine with icodextrin or standard glucose solution exchange.

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    Czupryniak, Aneta; Nowicki, Michal; Chwatko, Grazyna; Jander, Anna; Bald, Edward

    2005-12-01

    The aim of the study was to assess plasma homocysteine concentration in peritoneal dialysis patients, and to compare the effect of different peritoneal solutions (glucose-based and icodextrin-based) on peritoneal clearance of homocysteine. The study group comprised 10 chronic peritoneal dialysis patients; the control group comprised 15 healthy, age-matched non-obese subjects with normal renal function. Patients with vitamin B(12) or folate deficiency were excluded. In all subjects, plasma homocysteine and dialysis adequacy parameters were assessed at baseline. The clearance study was carried out with 2.27% glucose and 7.5% icodextrin solutions (12-h dwell time). Mean dialysate concentration of homocysteine was similar for both glucose and icodextrin solutions (8.3 +/- 3.2 and 8.4 +/- 1.9 micromol/L, respectively), but homocysteine clearance was significantly higher for icodextrin than glucose solution (1.82 +/- 0.57 vs 1.39 +/- 0.53 mL/min per 1.73 m(2)P = 0.01). Net ultrafiltration after icodextrin solution was also higher than after glucose solution (599 +/- 136 mL vs 134 +/- 337 mL, P Icodextrin-based solution for peritoneal dialysis seems to be more efficient in homocysteine elimination than a standard glucose-based solution.

  4. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

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    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  5. Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans.

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    Kaoru Ohashi

    Full Text Available Homeostatic control of blood glucose is regulated by a complex feedback loop between glucose and insulin, of which failure leads to diabetes mellitus. However, physiological and pathological nature of the feedback loop is not fully understood. We made a mathematical model of the feedback loop between glucose and insulin using time course of blood glucose and insulin during consecutive hyperglycemic and hyperinsulinemic-euglycemic clamps in 113 subjects with variety of glucose tolerance including normal glucose tolerance (NGT, impaired glucose tolerance (IGT and type 2 diabetes mellitus (T2DM. We analyzed the correlation of the parameters in the model with the progression of glucose intolerance and the conserved relationship between parameters. The model parameters of insulin sensitivity and insulin secretion significantly declined from NGT to IGT, and from IGT to T2DM, respectively, consistent with previous clinical observations. Importantly, insulin clearance, an insulin degradation rate, significantly declined from NGT, IGT to T2DM along the progression of glucose intolerance in the mathematical model. Insulin clearance was positively correlated with a product of insulin sensitivity and secretion assessed by the clamp analysis or determined with the mathematical model. Insulin clearance was correlated negatively with postprandial glucose at 2h after oral glucose tolerance test. We also inferred a square-law between the rate constant of insulin clearance and a product of rate constants of insulin sensitivity and secretion in the model, which is also conserved among NGT, IGT and T2DM subjects. Insulin clearance shows a conserved relationship with the capacity of glucose disposal among the NGT, IGT and T2DM subjects. The decrease of insulin clearance predicts the progression of glucose intolerance.

  6. Renal I-131-hippurate clearance overestimates true renal blood flow in the instrumented conscious dog

    NARCIS (Netherlands)

    Visscher, CA; DeZeeuw, D; Navis, G; VanZanten, AK; DeJong, PE; Huisman, RM

    1996-01-01

    We evaluated renal I-131-hippurate clearance (ERPF(hip)) as a measure of renal blood flow (RBF) in chronically instrumented conscious dogs. When adjusted for renal hippurate extraction (E(hip), 0.77 +/- 0.01) and hematocrit (Hct, 39.7 +/- 1%), calculated RBF(hip) (656 +/- 37 ml/min) markedly exceede

  7. CLEARANCE OF INDOMETHACIN OCCURS PREDOMINANTLY BY RENAL GLUCURONIDATION

    NARCIS (Netherlands)

    MOOLENAAR, F; CRANCRINUS, S; VISSER, J; DEZEEUW, D; MEIJER, DKF

    1992-01-01

    In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indometacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to

  8. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance

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    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R. James; Whelan, Eoin C.; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-01

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 109 M-1 cm-1 and 1.5 × 108 M-1 cm-1 respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  9. In Vivo Renal Clearance, Biodistribution, Toxicity of Gold nanoclusters

    CERN Document Server

    Zhang, Xiao-Dong; Shen, Xiu; Liu, Pei-Xun; Fan, Fei-Yue; Fan, Sai-Jun; 10.1016/j.biomaterials.2012.03.020

    2012-01-01

    Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 hours and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of gold can be cleared after 24 hours. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney fu...

  10. Quinidine does not affect the renal clearance of moxonidine

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    Wise, Stephen D; Chan, Clark; Schaefer, Hans G; He, Minxia M; Pouliquen, Isabelle J; Mitchell, Malcolm I

    2002-01-01

    Aims To test the hypothesis that the renal clearance of moxonidine decreases when dosed with quinidine. Methods A randomized, two-period study was conducted with six healthy, male subjects orally dosed with either 0.2 mg moxonidine alone or 1 h after 400 mg quinidine sulphate. Pharmacokinetic parameters were calculated using a noncompartmental analysis method. Results When coadministered, quinidine significantly increased moxonidine AUC and t1/2 by 11% and 15%, respectively, and decreased CL/F by 10% compared with the control dosing. CLR and Aeur were not significantly different. Clinically, both treatments were well tolerated. Conclusions Quinidine does not affect the renal clearance of moxonidine. The decrease in apparent total clearance of moxonidine with quinidine coadministration was possibly due to metabolic inhibition, though not likely to be clinically significant. PMID:12236844

  11. Renal clearance of pancreatic and salivary amylase relative to creatinine in patients with chronic renal insufficiency.

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    Keogh, J B; McGeeney, K F; Drury, M I; Counihan, T B; O'Donnell, M D

    1978-12-01

    Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.

  12. RENAL CLEARANCE AND URINARY EXCRETION OF CIPROFLOXACIN IN GOATS

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    Z. IQBAL, I. JAVED, B. ASLAM, F. MUHAMMAD AND I. U. JAN

    2007-10-01

    Full Text Available The renal clearance and urinary excretion of ciprofloxacin were investigated in eight healthy female goats. In each animal, ciprofloxacin was administered intramuscularly at the rate of 5 mg/kg body weight. Following drug administration, blood and urine samples were collected at different time intervals and analyzed for ciprofloxacin and creatinine. High performance liquid chromatography (HPLC was used to determine the drug concentration in the plasma and urine. The value of diuresis after single administration of ciprofloxacin was 0.073 ± 0.014 ml/min/kg. Mean (± SE values for renal clearance of creatinine and ciprofloxacin were 1.870 ± 0.385 and 0.982 ± 0.166 ml/min/kg, respectively. The ratio between the renal clearance of ciprofloxacin and that of creatinine remained less than one, which was indicative of back diffusion. The mean (± SE value for the cumulative percent of ciprofloxacin dose excreted at 10 hours following its intramuscular administration was 13.03 ± 2.07. Based on these results, it was evident that besides glomerular filtration, renal handling of drug involved back diffusion also. It was concluded that in local goats glomerular filtration rate (GFR was lower than that reported for their foreign counterparts.

  13. Online feedback-controlled renal constant infusion clearances in rats.

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    Schock-Kusch, Daniel; Shulhevich, Yury; Xie, Qing; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Friedemann, Jochen; Koenig, Stefan; Heinrich, Ralf; Hoecklin, Friederike; Pill, Johannes; Gretz, Norbert

    2012-08-01

    Constant infusion clearance techniques using exogenous renal markers are considered the gold standard for assessing the glomerular filtration rate. Here we describe a constant infusion clearance method in rats allowing the real-time monitoring of steady-state conditions using an automated closed-loop approach based on the transcutaneous measurement of the renal marker FITC-sinistrin. In order to optimize parameters to reach steady-state conditions as fast as possible, a Matlab-based simulation tool was established. Based on this, a real-time feedback-regulated approach for constant infusion clearance monitoring was developed. This was validated by determining hourly FITC-sinistrin plasma concentrations and the glomerular filtration rate in healthy and unilaterally nephrectomized rats. The transcutaneously assessed FITC-sinistrin fluorescence signal was found to reflect the plasma concentration. Our method allows the precise determination of the onset of steady-state marker concentration. Moreover, the steady state can be monitored and controlled in real time for several hours. This procedure is simple to perform since no urine samples and only one blood sample are required. Thus, we developed a real-time feedback-based system for optimal regulation and monitoring of a constant infusion clearance technique.

  14. Spontaneous Clearance of Hepatitis C after Liver and Renal Transplantation

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    CH Dale

    2009-01-01

    Full Text Available Spontaneous clearance of hepatitis C virus (HCV is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

  15. [Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?].

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    Dhia, Rym Ben; Hellara, Ilhem; Harzallah, Olfa; Neffati, Fadoua; Khochtali, Ines; Mahjoub, Sylvia; Najjar, Mohamed Fadhel

    2012-01-01

    Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients.

  16. Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

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    Hull, Kerry

    2016-01-01

    Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

  17. Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance.

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    Steiner, G; Wilson, D; Vranic, M

    1977-01-01

    Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct

  18. Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

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    Maria Adelaide Marini

    Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

  19. Highly Catalytic Nanodots with Renal Clearance for Radiation Protection

    CERN Document Server

    Zhang, Xiao-Dong; Wang, Junying; Yang, Jiang; Chen, Jie; Shen, Xiu; Deng, Jiao; Deng, Dehui; Long, Wei; Sun, Yuan-Ming; Liu, Changlong; Li, Meixian

    2016-01-01

    Ionizing radiation (gamma and x-ray) is widely used in industry and medicine, but it can also pose a significant hazardous effect on health and induce cancer, physical deformity and even death, due to DNA damages and invasion of free radicals. There is therefore an urgent unmet demand in designing highly efficient radioprotectants with synergetic integration of effective renal clearance and low toxicity. In this study, we designed ultrasmall (sub-5 nm) highly catalytically active and cysteine-protected MoS2 dots as radioprotectants and investigated their application in protection against ionizing radiation. In vivo preclinical studies showed that the surviving fraction of MoS2-treated mice can appreciably increase to up to 79 % when they were exposed to high-energy ionizing radiation. Furthermore, MoS2 dots can contribute in cleaning up the accumulated free radicals within the body, repairing DNA damages and recovering all vital chemical and biochemical indicators, suggesting their unique role as free radical...

  20. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, N V; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    .00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium......, increase baseline values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)...

  1. Hormonal regulation of glucose clearance in lactating northern elephant seals (Mirounga angustirostris).

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    Fowler, Melinda A; Champagne, Cory D; Houser, Dorian S; Crocker, Daniel E

    2008-09-01

    Northern elephant seals exhibit the rare strategy of fasting and lactating concomitantly. We investigated hormonal regulation of glucose clearance in northern elephant seals using glucose tolerance tests (GTT) performed early in lactation and again just prior to weaning. For comparison, identical measurements were made on separate females late in the molt fast. Serial blood samples were used to assess glucose clearance and hormone responses for 3 h post glucose injection. Plasma glucose remained elevated at the end of the sampling period in all groups. Glucose clearance rates were not significantly different among test groups. A significant insulin response was observed in early lactation, no significant response was observed late in lactation and an intermediate response was observed late in the molt fast. The insulin response to a glucose load decreased with adipose tissue proportions. Plasma glucagon decreased significantly following GTT in early and late lactation, although the magnitude of the depression was small in comparison to other species. Hypoinsulemia may be critical to facilitate net lipolysis late in lactation. Consistently low glucose clearance among test groups suggests insulin insensitivity within peripheral tissues. Glucagon suppression independent of insulin release suggests modification of the typical insulin-glucagon counter-regulation. These findings suggest that metabolic features of diabetic-like conditions may be adaptive in the context of long-term fasting.

  2. Assessment of compensatory renal function and [125I]iothalamate clearance in sheep.

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    Filippich, L J; English, P B; Ainscow, J

    1985-11-01

    Compensatory renal function and sodium [125I]iothalamate clearance were studied in 4 adult Merino ewes. Renal clearances of inulin (CIN), iothalamate (CIOT), and p-aminohippurate (CPAH) were used to measure renal function before and 7 and 170 days after 50% and 75% reductions in renal mass. Renal mass reduction to 50% of normal was achieved by ligation of the right renal artery, and to 25% of normal by ligating the right renal artery and branches of the left renal artery. Renal function (CIN and CPAH) after 50% renal mass reduction was 78% of normal on postligation day (PLD) 7 and 64% of normal on PLD 170. This decrease in renal function between PLD 7 and 170 was significant (P less than 0.05). Renal function (CIN and CPAH) after 75% renal mass reduction was 55% of normal on PLD 7 and 48% on PLD 170; however, this decrease in renal function between PLD 7 and 170 was not significant. Results indicated that, shortly after 50% renal mass reduction by renal arterial ligation, renal function in ewes was greater than that previously reported after unilateral nephrectomy and that a further decrease in renal function developed within 6 months after ligation. The mean CIOT in healthy ewes was 2.46 ml/min/kg of body weight. In healthy ewes and in ewes after renal mass reduction, regression of the simultaneous CIOT and CIN was CIOT = 0.276 + 1.05 CIN. The CIOT was higher than the corresponding CIN, and remained significantly (P less than 0.01) and consistently higher. Therefore, iothalamate can be used to estimate glomerular filtration rate in sheep, although a correction factor is required.

  3. Amylase-creatinine clearance ratios and serum amylase isoenzymes in moderate renal insufficiency.

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    Banks, P A; Sidi, S; Gelman, M L; Lee, K H; Warshaw, A L

    1979-12-01

    Both the amylase-creatinine clearance ratio (normal 1.55%) and proportion of pancreatic isoamylase in serum (normal 41.0%) increase in acute pancreatitis, and are therefore useful measurements to support that diagnosis. Whether renal insufficiency interferes with the accuracy and specificity of these tests has been debated. Our study indicates that even moderate renal insufficiency (creatinine clearance 30.5 ml/minute) raises the amylase-creatinine clearance ratio (3.23%) close enough to values characteristic of acute pancreatitis (4.41%) to cause potential diagnostic confusion. The fraction of pancreatic isoamylase in serum is also increased (69.9%), but not to the levels of acute pancreatitis (91.0%). We therefore caution against the use of the amylase-creatinine clearance ratio for the diagnosis of acute pancreatitis in patients with moderate renal insufficiency.

  4. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    .00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium.......05) and 10% (P sodium clearance were significantly diminished after 450mg (P ... values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)...

  5. Serum amylase activity and renal amylase activity clearance in patients with severely impaired renal function and in patients treated with renal allotransplantation.

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    Pedersen, E B; Brock, A; Kornerup, H J

    1976-03-01

    Serum amylase activity was measured in 29 nondialysed patients with severe renal failure, in 24 uraemic patients treated with chronic haemodialysis, and in 29 patients treated with renal allotransplantation. Simultaneous measurement of renal amylase activity clearance (CAm) and creatinine clearance (CCr) was performed in 25 patients with severe renal failure and in 19 transplanted patients. Serum amylase activity was elevated in all three groups. CAm was significantly correlated to CCr both in the group with severe renal failure and in the transplanted group. Unlike in the group of transplanted patients, the ratio CAm/CCr was significantly increased in patients with severe impaired renal function. It is concluded that the elevation of serum amylase activity in patients with impaired renal function is primarily due to decreased glomerular filtration rate. The value of CAm/CCr for diagnosing acute pancreatitis is doubtful in patients with severe renal disease.

  6. Serum amylase determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency.

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    Tedesco, F J; Harter, H R; Alpers, D H

    1976-10-01

    Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.

  7. Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

    DEFF Research Database (Denmark)

    Jensen, Michael Gejl; Egefjord, Lærke; Lerche, Susanne

    2012-01-01

    and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males. Positron emission tomography was used to determine the effect of GLP-1 on cerebral glucose transport and metabolism...... across the blood–brain barrier remained unchanged (P=0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased (P=0.013 and 0.017), leading to increased net clearance of the glucose tracer (P=0.006). We show that GLP-1 plays a role in a regulatory mechanism involved......Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD...

  8. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    Science.gov (United States)

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. Copyright © 2016 the American Physiological Society.

  9. Effect of glucagon infusion on the renal clearance of amylase relative to creatinine.

    Science.gov (United States)

    Tedesco, F J; Davila, E; Gardner, L B

    1978-10-01

    Recent data seem to support a tubular defect as the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon has been proposed by some to be an important factor in this phenomenon. To examine the role of glucagon as this "tubular dysfunction factor", we investigated the effect of intravenously infused glucagon on the fractional excretion of amylase and the tubular handling of a low molecular weight protein, beta2 microglobulin, in normal, healthy volunteers. At glucagon levels far in excess of those seen in pancreatitis, the clearance ratio of beta2 microglobulin relative to creatinine increased, whereas the clearance ratio of amylase relative to creatinine did not increase above the normal range. The dissociation between beta2 microglobulin clearance and amylase clearance allows one to question the theory that tubular dysfunction is the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon does not appear to be the sole factor responsible for the elevation of renal clearance of amylase relative to creatinine in acute pancreatitis.

  10. Glucose clearance is higher in arm than leg muscle in type 2 diabetes

    DEFF Research Database (Denmark)

    Olsen, David B; Sacchetti, Massimo; Dela, Flemming;

    2005-01-01

    Insulin-mediated glucose clearance (GC) is diminished in type 2 diabetes. Skeletal muscle has been estimated to account for essentially all of the impairment. Such estimations were based on leg muscle and extrapolated to whole body muscle mass. However, skeletal muscle is not a uniform tissue......). At basal, CON had 84% higher arm GC (P=0.012) and 87% higher leg GC (P=0.016) compared with TYPE 2. During clamp, the difference between CON and TYPE 2 in arm GC was diminished to 54% but maintained at 80% in the leg. In conclusion, this study shows that glucose clearance is higher in arm than leg muscles...

  11. High Phenobarbital Clearance During Continuous Renal Replacement Therapy

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-01-01

    Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

  12. Effects of hyperventilation and hypocapnic/normocapnic hypoxemia on renal function and lithium clearance in humans

    DEFF Research Database (Denmark)

    Christensen, H; Klausen, T; Fogh-Andersen, N;

    1998-01-01

    Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapni...

  13. Time-dependent clearance of mycophenolic acid in renal transplant recipients

    NARCIS (Netherlands)

    R.M. van Hest (Reinier); T. van Gelder (Teun); R. Bouw (René); T. Goggin (Timothy); R. Gordon (Robert); R. Mamelok (Richard); R.A. Mathot (Ron)

    2007-01-01

    textabstractAims: Pharmacokinetic studies of the immunosuppressive compound mycophenolic acid (MPA) have shown a structural decrease in clearance (CL) over time after renal transplantation. The aim of this study was to characterize the time-dependent CL of MPA by means of a population pharmacokineti

  14. The mechanism of increased renal clearance of amylase in acute pancreatitis.

    Science.gov (United States)

    Warshaw, A L; Lee, K H

    1976-09-01

    Amylase isoenzymes, separated by polyacrylamide gel electrophoresis, were measures in 25 normal persons (mean amylase to creatinine clearance ratio 3.0%), 15 patients with acute pancreatitis (mean clearance ratio 9.5%, P less than 0.0001), and 6 patients with hyperamylasemia due to common duct stones (mean clearance ratio 4.1%). Two isoamylases (P1, P2) resembling pancreatic isoenzymes and three isoamylases (S1, S2, S3) resembling salivary isoenzymes appeared regularly in normal serum and urine. Salivary amylases predominated in serum, but pancreatic amylases predominated in urine. This finding is consistent with renal clearance of pancreatic amylases exceeding that of salivary amylases under normal conditions. In patients with pancreatitis or common duct stones, essentially all of the increased amylase activity in serum and urine was due to pancreatic isoamylases (P1 and P2) in their normal proportions. No new or altered amylase isoenzymes were detected. The fraction of pancreatic amylases in the serum or urine was identical for the two diseases. Whereas the difference in amylase to creatinine clearance ratios observed between the two groups of patients is not a function of different amylase isoenzymes presented to the kidney, we conclude that the increased amylase clearance in acute pancreatitis is caused by an alteration of renal transfer of amylase, either at the glomerulus or tubule.

  15. Increasing Haemodialytic Clearances as Residual Renal Function Declines: An Incremental Approach.

    Science.gov (United States)

    Tangvoraphonkchai, Kamonwan; Davenport, Andrew

    2017-08-16

    Many patients with chronic kidney disease start undergoing thrice-weekly haemodialysis (HD), aiming for an HD sessional dialyzer urea clearance target, irrespective of whether they have residual renal function (RRF). While increasing sessional dialyzer urea clearance above a target of 1.2 has not been shown to improve patient survival, it has been shown that the preservation of RRF improves patient self-reported outcomes and survival. Observational studies have suggested that initiating twice-weekly HD schedules leads to greater preservation of RRF. This has led to the concept of following an incremental approach to initiating HD, steadily increasing the amount of weekly dialyzer clearance as RRF decreases. Incremental dialysis practice requires the regular assessment of RRF to prevent inadequate delivery of dialysis treatment. Once RRF is lost, then the dialysis schedule and modality need to be adjusted to try to increase the middle-sized solute clearance and protein-bound toxins. © 2017 S. Karger AG, Basel.

  16. Renal scintigraphy and clearance before and after transluminal angioplasty of a renal artery stenosis. Nierenfunktions-Szintigraphie und Clearance zur Erfolgsbeurteilung einer transluminalen Angioplastie bei Nierenarterienstenosen

    Energy Technology Data Exchange (ETDEWEB)

    Maul, F.D.; Baum, R.P.; Hoer, G.; Standke, R. (Frankfurt Univ. (Germany). Abt. fuer Nuklearmedizin)

    1991-12-01

    Nuclear medicine results before, early and late after percutaneous transluminal angioplasty (PTA) were evaluated. On the one hand this study was based on the results of the I-131-Hippuran clearance according to Oberhausen, including the time to maximum (Tmax) and half life time of renal elimination (EHWZ). On the other hand data from renal scintigraphy with Tc-99m-DTPA (perfusion and nephrographic phase) were used. Values of all split functions exhibit a progressive improvement between early and late controls. Glomerular filtration fraction (GFR) of the post-stenotic kidney increases immediately after PTA from 30% (before) to 35% (early after). EHWZ (before 17.6, early after 14.1, late after 10,8 min) and Tmax inversely correlat with GFR. I-131-Hippuran clearance indicates only a late increase (before 306, early after 309, late after 317 ml/min). According to this retrospective study GFR as well as Tmax and EHWZ (partially GFR dependent parameters) are most suitable in the follow up after PTA of a renal artery stenosis. (orig.).

  17. Macroamylasemia with a markedly increased amylase clearance ratio in a patient with renal cell carcinoma.

    Science.gov (United States)

    Kazmierczak, S C; Van Lente, F; McHugh, A M; Katzin, W E

    1988-02-01

    We report hyperamylasemia, macroamylasemia, and a markedly increased amylase clearance/creatinine clearance ratio in a patient with renal cell carcinoma. Serum amylase activity was characterized as macroamylase by gel exclusion chromatography. Electrophoretic separation revealed an atypical band of amylase, migrating anodal to the S2 control fraction. Electrophoresis of urine revealed the presence of both S1 and S2 fractions, but not the atypical band found in serum. Quantification of the salivary- and pancreatic-type amylase fractions showed amylase in urine to be 100% salivary. Immunofixation disclosed the macroamylase to consist of an immune complex between amylase and IgA-lambda antibody. Binding-capacity studies showed that the serum immunoglobulin was present in excess and could bind 46% and 49% additional S-type amylase activity derived from saliva and the patient's urine, respectively. The amylase clearance/creatinine clearance ratio was markedly supranormal (0.134), unexpected in a patient with macroamylasemia. A biopsy specimen of the renal cell tumor was found to contain significant salivary-type amylase activity. These results suggest production of amylase by tumor tissue in the renal carcinoma and secretion of S-type amylase into the patient's urine. Evidently, macroamylase should be confirmed by gel exclusion chromatography.

  18. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J

    1999-01-01

    clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P exercise, leg......Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle...... +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose...

  19. [Study of age and sex dependance in renal clearances with radioisotopes (author's transl)].

    Science.gov (United States)

    Schernthaner, G; Erd, W; Ludwig, H; Sinzinger, H; Höfer, R

    1976-03-01

    In 85 patients between 15 and 95 years of age (40 male patients and 45 females) without any signs of renal disease (concentration of serum creatinine below 1,4 mg/100ml, normal diastolic blood pressure and normal urine analysis) a highly significant negative correlation was found between glomerular filtration rate (GFR, determined by 51Cr-EDTA - slope-clearance) and renal plasma flow (RPF, determined by 131J-oJHS-iodinehippuricacid-totalclearance) on one side and age on the other. Beginning with a basic value of 160 ml in males and 144 ml in females for GFR, the average decrease per year was 1,2 ml/1,0 ml respectively. The basis value of RPF was 854 ml for males and 673 ml for females, the decrease per year was 5,4 ml in men and 2,9 ml in women. The importance of physiological diminution of clearance values in elderly patients and its consequences for therapy are discussed. The more exact and methodically simpler 51Cr-EDTA-slope-clearance without urine collection should be used instead of the somewhat inaccurate determination of endogenous creatinine clearance especially in older patients.

  20. Renal Drug Dosage Adjustment According to Estimated Creatinine Clearance in Hospitalized Patients With Heart Failure.

    Science.gov (United States)

    Altunbas, Gokhan; Yazc, Mehmet; Solak, Yalcin; Gul, Enes E; Kayrak, Mehmet; Kaya, Zeynettin; Akilli, Hakan; Aribas, Alpay; Gaipov, Abduzhappar; Yazc, Raziye; Ozdemir, Kurtulus

    2016-01-01

    It is of clinical importance to determine creatinine clearance and adjust doses of prescribed drugs accordingly in patients with heart failure to prevent untoward effects. There is a scarcity of studies in the literature investigating this issue particularly in patients with heart failure, in whom many have impaired kidney function. The purpose of this study was to determine the degree of awareness of medication prescription as to creatinine clearance in patients hospitalized with heart failure. Patients hospitalized with a diagnosis of heart failure were retrospectively evaluated. Among screened charts, patients with left ventricular ejection fraction renal dose adjustment were determined and evaluated for appropriate dosing according to eGFR. A total of 388 patients with concomitant heart failure and renal dysfunction were included in the study. The total number of prescribed medications was 2808 and 48.3% (1357 medications) required renal dose adjustment. Of the 1357 medications, 12.6% (171 medications) were found to be inappropriately prescribed according to eGFR. The most common inappropriately prescribed medications were famotidine, metformin, perindopril, and ramipril. A significant portion of medications used in heart failure requires dose adjustment. Our results showed that in a typical cohort of patients with heart failure, many drugs are prescribed at inappropriately high doses according to creatinine clearance. Awareness should be increased among physicians caring for patients with heart failure to prevent adverse events related to medications.

  1. 51Cr-EDTA plasma clearance in severe renal failure determined by one plasma sample

    DEFF Research Database (Denmark)

    Kamper, A L; Nielsen, S L

    1989-01-01

    at zero-time was derived from injected dose and body surface area. This method might provide values 1.5 ml/min below or 0.8 ml/min above the established method of 51Cr-EDTA plasma clearance, which would be acceptable for clinical purposes. It is concluded that exact plasma clearance of 51Cr-EDTA in severe......Two hundred and thirty-four measurements of standard 51Cr-EDTA plasma clearance were made in 50 patients with severe chronic renal failure. Based on these data two calculation methods were attempted using one plasma sample drawn 24 h after injection of 51Cr-EDTA. One of the methods used the 'one...... sample clearance' formulas disregarding exact time of plasma sampling. This method might provide values 3.1 ml/min below or 2.9 ml/min above the established method of total 51Cr-EDTA plasma clearance, and would thus provide insufficient agreement. In the other method an estimate of plasma activity...

  2. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

    DEFF Research Database (Denmark)

    Bruun, N E; Ibsen, H; Skøtt, P

    1988-01-01

    1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155...... reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment...

  3. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Devineni, Damayanthi; Curtin, Christopher R; Marbury, Thomas C; Smith, William; Vaccaro, Nicole; Wexler, David; Vandebosch, An; Rusch, Sarah; Stieltjes, Hans; Wajs, Ewa

    2015-03-01

    Canagliflozin is a sodium-glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). Because T2DM is often associated with renal or hepatic impairment, understanding the effects of these comorbid conditions on the pharmacokinetics of canagliflozin, and further assessing its safety, in these special populations is essential. Two open-label studies evaluated the pharmacokinetics, pharmacodynamics (renal study only), and safety of canagliflozin in participants with hepatic or renal impairment. Participants in the hepatic study (8 in each group) were categorized based on their Child-Pugh score (normal hepatic function, mild impairment [Child-Pugh score of 5 or 6], and moderate impairment [Child-Pugh score of 7-9]) and received a single oral dose of canagliflozin 300 mg. Participants in the renal study (8 in each group) were categorized based on their creatinine clearance (CLCR) (normal renal function [CLCR ≥80 mL/min]; mild [CLCR 50 to canagliflozin 200 mg; the exception was those with ESRD, who received 1 dose postdialysis and 1 dose predialysis (10 days later). Canagliflozin's pharmacokinetics and pharmacodynamics (urinary glucose excretion [UGE] and renal threshold for glucose excretion [RTG]) were assessed at predetermined time points. Mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinite (AUC)0-∞ values differed by Canagliflozin's pharmacokinetics were not affected by mild or moderate hepatic impairment. Systemic exposure to canagliflozin increased in the renal impairment groups relative to participants with normal renal function. Pharmacodynamic response to canagliflozin, measured by using UGE and RTG, declined with increasing severity of renal impairment. A single oral dose of canagliflozin was well tolerated by participants in both studies. ClinicalTrials.gov identifiers: NCT01186588 and NCT01759576. Copyright © 2015 Elsevier HS Journals, Inc. All rights

  4. RENAL CLEARANCE AND URINARY EXCRETION OF KANAMYCIN IN DOMESTIC RUMINANT SPECIES

    Directory of Open Access Journals (Sweden)

    I. JAVED, Z. U. RAHMAN, F. H. KHAN, F. MUHAMMAD, Z. IQBAL AND B. ASLAM

    2006-01-01

    Full Text Available Species dependent geonetical differences in renal clearance and urinary excretion of kanamycin were investigated in adult female buffaloes, cows, sheep and goats. The drug was administered as a single intravenous dose (5 mg/kg b.wt. Blood and urine samples were collected at various time intervals after drug administration. The plasma and urine concentrations of the drug were determined using the microbiological assay. The mean (± SE values for endogenous creatinine clearance (an index of glomerular filtration rate were 0.77 ± 0.05, 0.49 ± 0.07, 0.81 ± 0.07 and 0.98 ± 0.13 ml/min.kg in buffaloes, cows, sheep and goats, respectively. Experiments regarding kidney handling of kanamycin in these ruminant species revealed respective values of renal clearance as 0.08 ± 0.01, 0.07 ± 0.01, 0.19 ± 0.02 and 0.23 ± 0.04 ml/min.kg. Besides glomerular filtration, kanamycin was reabsorbed from the renal tubules of all ruminant species and actively secreted into the renal tubules of buffaloes and goats. The cumulative percentages of intravenous dose of kanamycin excreted through urine during 12 hours in buffaloes, cows, sheep and goats were 4.31 ± 0.37, 2.53 ± 0.30, 11.0 ± 1.04 and 15.8 ± 2.22, respectively. This species variation in the percentage of urinary excretion in these domestic ruminants coincides with their respective glomerular filtration rates, being the highest in goats, lowest in cows and intermediate in sheep and buffaloes.

  5. TECHNETIUM-99M-MAG3 CLEARANCE AS A PARAMETER OF EFFECTIVE RENAL PLASMA-FLOW IN PATIENTS WITH PROTEINURIA AND LOWERED SERUM-ALBUMIN LEVELS

    NARCIS (Netherlands)

    KENGEN, RA; MEIJER, S; BEEKHUIS, H; PIERS, DA

    1991-01-01

    Although the renal clearance of Tc-99m-MAG3 is about 60% of the I-131-hippurate clearance, Tc-99m-MAG3 clearance may be useful to estimate ERPF. In one study, however, proteinuria seemed to influence the MAG3/hippurate clearance ratio. In order to establish whether proteinuria or serum albumin level

  6. Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

    Directory of Open Access Journals (Sweden)

    Zhang XD

    2014-04-01

    Full Text Available Xiao-Dong Zhang,1 Jiang Yang,2 Sha-Sha Song,1 Wei Long,1 Jie Chen,1 Xiu Shen,1 Hao Wang,1 Yuan-Ming Sun,1 Pei-Xun Liu,1 Saijun Fan11Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI, USAAbstract: The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.Keywords: in vivo clearance, gold nanoparticles, small size

  7. Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110.

    Science.gov (United States)

    Zhang, Yan; Warren, Mark S; Zhang, Xuexiang; Diamond, Sharon; Williams, Bill; Punwani, Naresh; Huang, Jane; Huang, Yong; Yeleswaram, Swamy

    2015-04-01

    Serum creatinine is commonly used as a marker of renal function, but increases in serum creatinine might not represent changes in glomerular filtration rate (GFR). INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine was observed after treatment with INCB039110. However, a dedicated renal function study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy volunteers indicated no change in GFR. In vitro studies were therefore conducted to investigate the interaction of INCB039110 with five transporters that are likely involved in the renal clearance of creatinine. Cell systems expressing individual or multiple transporters were used, including a novel quintuple-transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of creatinine. Given the interactions of INCB039110 with multiple transporters affecting creatinine uptake and efflux, an integrated system expressing all five transporters was sought; in that system, INCB039110 caused a dose-dependent decrease in transcellular transport of creatinine with weaker net inhibition compared with the effects on individual transporters. In summary, a molecular mechanism for the increase in serum creatinine by INCB039110 has been established. These studies also underline the limitations of using serum creatinine as a marker of renal function.

  8. Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension.

    Science.gov (United States)

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1995-01-01

    The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance while treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  9. Quantitation of renal function with 99Tcm-DMSA. A comparison with creatinine clearance in children with single kidney.

    Science.gov (United States)

    Baillet, G; Gagnadoux, M F; De Vernejoul, P; Broyer, M

    1985-11-01

    To study the accuracy of renal function quantification with 99Tcm-DMSA we compared DMSA renal uptake and creatinine clearance in 16 cases of children with single kidney. The age of the patients ranged from two months to fourteen years. Creatinine clearance was normalized to 1.73 m2. DMSA uptake was measured 7 h after intravenous injection. Background subtraction was used and soft tissue attenuation was taken into account. The uptake was normalized in percentage of the injected activity. A significant correlation was found between creatinine clearance and DMSA uptake (rt = 0.866, p less than 0.01). Normal creatinine clearance range in children (80 to 120 ml min-1/1.73 m2) allowed determination of normal uptake range (36 to 60%). This study indicates that in case of asymmetrical renal impairment renal uptake will reflect split renal creatinine clearance. Since the former is much easier to measure, DMSA should play an important role in the evaluation of differential renal function.

  10. Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared photothermal cancer therapy.

    Science.gov (United States)

    Tang, Shaoheng; Chen, Mei; Zheng, Nanfeng

    2014-08-13

    Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra-small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (photothermal therapy, the unique renal clearance properties make the ultra-small Pd nanosheets promising for practical use in photothermal cancer therapy.

  11. Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

    Directory of Open Access Journals (Sweden)

    Menegon L.F.

    1998-01-01

    Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

  12. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3

    OpenAIRE

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-01-01

    Abstract Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigat...

  13. Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

    DEFF Research Database (Denmark)

    Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

    2002-01-01

    The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin......-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

  14. Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin.

    Science.gov (United States)

    Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E; Fyfe, John C; Nowacki, Wojciech; Jacobsen, Christian; Moestrup, Søren K; Christensen, Erik I

    2002-02-01

    The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN-16 cells was inhibited by anti-megalin and anti-cubilin antibodies as well as by receptor-associated protein, a chaperone for LDL-receptor family proteins. Partial inhibition by myoglobin was observed, whereas bovine serum albumin, intrinsic factor-cobalamin complexes, and beta2-microglobulin did not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic clearance of hemoglobin. Labeling intensities in kidneys from normal and cubilin-malexpressing dogs were similar, which suggests that, in the normal state, the role of cubilin in uptake of hemoglobin is rather limited. However, cubilin is likely to assist hemoglobin endocytosis in settings of hemoglobinuria. In conclusion, the study provides a molecular explanation for long-standing observations of hemoglobin uptake in renal proximal tubules that involve the endocytic receptors megalin and cubilin. The findings may prove to be essential for further research on the pathophysiology of hemoglobinuric acute renal failure and proteinuria-associated tubulointerstitial nephritis.

  15. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

    Directory of Open Access Journals (Sweden)

    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  16. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy

    Science.gov (United States)

    Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H.; Roy, Shuvo

    2015-01-01

    Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of the SNM’s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-corporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1 fold increase and 1.8 fold increase over polyethylene-glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD-41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401

  17. Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats.

    Science.gov (United States)

    Lee, Unji; Lee, Inchul; Lee, Byung K; Kang, Hee E

    2013-11-20

    Metoprolol is a selective β1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). In this study, we evaluated pharmacokinetic changes following intravenous (i.v.) and oral metoprolol in rats with diabetes mellitus induced by streptozotocin (DMIS). Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism. Thus, the hepatic clearance, CL(H) (the non-renal clearance, CL(NR)) of metoprolol depends on the hepatic blood flow rate (Q(H)), the free fraction in plasma (f(p)), and in vitro hepatic intrinsic clearance, CL(int). After i.v. administration of 1.5 mg/kg metoprolol to DMIS rats, its CLNR was 40.9% faster than control animals. This could be due to a significantly faster QH because hepatic CL(int) and fp were comparable between the two groups of rats due to unchanged hepatic CYP2D activity. After oral administration of 1.5 mg/kg metoprolol to DMIS rats, gastrointestinal absorption was >99% of the oral dose for both groups, while the area under the curve (AUC) was 27.9% smaller, which could be caused by the greater hepatic metabolism seen in the i.v. study. These findings have potential therapeutic implications, assuming that the DMIS rats qualitatively reflect similar changes in patients with diabetes.

  18. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy.

    Science.gov (United States)

    Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H; Roy, Shuvo

    2016-01-01

    Silicon nanopore membranes (SNMs) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here, we present an initial evaluation of the SNM's mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200 ml/min) and pressures (1,448 mm Hg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25 ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4 hours in an extracorporeal porcine model. The pressure drop across the flow cell was 4.6 mm Hg at 200 ml/min. Mechanical testing showed that SNM could withstand up to 775.7 mm Hg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extracorporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1-fold increase and 1.8-fold increase over polyethylene glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy.

  19. Four hour creatinine clearance is better than plasma creatinine for monitoring renal function in critically ill patients

    OpenAIRE

    Pickering, John W.; Frampton, Christopher M; Walker, Robert J; Shaw, Geoffrey M; Endre, Zoltán H

    2012-01-01

    Introduction Acute kidney injury (AKI) diagnosis is based on an increase in plasma creatinine, which is a slowly changing surrogate of decreased glomerular filtration rate. We investigated whether serial creatinine clearance, a direct measure of the glomerular filtration rate, provided more timely and accurate information on renal function than serial plasma creatinine in critically ill patients. Methods Serial plasma creatinine and 4-hour creatinine clearance were measured 12-hourly for 24 h...

  20. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  1. Quantitative Prediction of Human Renal Clearance and Drug-Drug Interactions of Organic Anion Transporter Substrates Using In Vitro Transport Data: A Relative Activity Factor Approach.

    Science.gov (United States)

    Mathialagan, Sumathy; Piotrowski, Mary A; Tess, David A; Feng, Bo; Litchfield, John; Varma, Manthena V

    2017-04-01

    Organic anion transporters (OATs) are important in the renal secretion, and thus, the clearance, of many drugs; and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured in vitro using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir), and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance (after physiologic scaling) to in vivo secretory clearance. Using the estimated RAFs (0.64, 7.3, and 4.1, respectively, for OAT1, OAT2, and OAT3, respectively) and the in vitro active clearances, renal secretory clearance and total renal clearance were predicted with average fold errors (AFEs) of 1.89 and 1.40, respectively. The results show that OAT3-mediated transport play a predominant role in renal secretion for 22 of the 31 drugs evaluated. This mechanistic static approach was further applied to quantitatively predict renal drug-drug interactions (AFE ∼1.6) of the substrate drugs with probenecid, a clinical probe OAT inhibitor. In conclusion, the proposed in vitro-in vivo extrapolation approach is the first comprehensive attempt toward mechanistic modeling of renal secretory clearance based on routinely employed in vitro cell models.

  2. Augmented renal clearance in septic patients and implications for vancomycin optimisation.

    Science.gov (United States)

    Baptista, João Pedro; Sousa, Eduardo; Martins, Paulo J; Pimentel, Jorge M

    2012-05-01

    The aim of this study was to evaluate the effect of augmented renal clearance (ARC) on vancomycin serum concentrations in critically ill patients. This prospective, single-centre, observational, cohort study included 93 consecutive, critically ill septic patients who started treatment that included vancomycin by continuous infusion, admitted over a 2-year period (March 2006 to February 2008). ARC was defined as 24-h creatinine clearance (CL(Cr))>130 mL/min/1.73 m(2). Two groups were analysed: Group A, 56 patients with a CL(Cr)≤130 mL/min/1.73 m(2); and Group B, 37 patients with a CL(Cr)>130 mL/min/1.73 m(2). Vancomycin therapeutic levels were assessed on the first 3 days of treatment (D(1), D(2) and D(3)). Serum vancomycin levels on D(1), D(2) and D(3), respectively, were 13.1, 16.6 and 18.6 μmol/L for Group A and 9.7, 11.7 and 13.8 μmol/L for Group B (P<0.05 per day). The correlation between CL(Cr) and serum vancomycin on D(1) was -0.57 (P<0.001). ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment.

  3. Creatinine clearance, urinary excretion of glomerular basement membrane antigens and renal histology in congenital nephrotic syndrome of Finnish type.

    Science.gov (United States)

    Huttunen, N P

    1977-04-01

    The endogenous creatinine clearance and urinary excretion rate of glomerular basement membrane (GBM) antigens were followed from 2 to 19 months in fifteen patients with congenital nephrotic syndrome (CNF). The quantitative examination of renal morphology was made on fourteen of these patients. Creatinine clearance increased during the first few months of life and thereafter gradually decreased. The urinary excretion rate of GBM antigens rose during the course of the disease. The creatinine clearance did not correlate significantly with glomerular fibrosis but it did correlate with tubular atrophy and interstitial fibrosis. The urinary excretion of GBM antigens correlated significantly with glomerular and interstitial fibrosis and with tubular atrophy. It is concluded that there is a clear progress in the disease and the renal histological changes probably are caused by accumulation of GBM material in glomeruli.

  4. Conventional measurements of GFR using {sup 51}Cr-EDTA overestimate true renal clearance by 10 percent

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Amelia E.B.; Park-Holohan, So-Jin; Blake, Glen M.; Fogelman, Ignac [Department of Nuclear Medicine, Guy' s Hospital, St Thomas Street, London, SE1 9RT (United Kingdom)

    2003-01-01

    It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid ({sup 51}Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that {sup 51}Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of {sup 51}Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45-79 years) were injected with 3 MBq {sup 51}Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0-2 h and 2-4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean {sup 51}Cr-EDTA total plasma clearance was 84 ml/min (range 50-132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3- and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, {alpha}{sub 0}, and the residual urine volume, {delta}V. The results were {alpha}{sub 0}=0.910 (95% CI: 0.889-0.932) and {delta}V=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of {sup 51}Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using {sup 51}Cr-EDTA overestimate the true renal clearance of tracer

  5. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    Science.gov (United States)

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  6. Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

    OpenAIRE

    Liu, Jiwen; Lee, TaeWeon; DeFronzo, Ralph A.

    2012-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokineti...

  7. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    Science.gov (United States)

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  8. Renal radioisotope clearance in an unselected group of diabetics - a tool for the early recognition of diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Doschek, D.; Wulf, R.; Krause, F.J.

    1980-12-01

    Our study in unselected patients with diabetes was undertaken to determine the relation between glomerular filtration rate (GFR) and renal plasma flow (RPF) according to the patient's age. The diagnostic work-up was done with patients in unselected disease states because a classification of all systemic manifestations of the diabetes was not possible. The lack of selection may therefore reduce the value of our statistical results. From age 55 onwards, there was a reduction in GFR and, to a lesser extent, in PFR exceeding that which was age-dependent. It is, therefore, recommended to check the clearance in all patients with diabetes older than 55 years. The clearance with radioisotopically labeled substances, being a very sensitive method for the evaluation of restricted renal function, may permit an early recognition of diabetic nephropathy.

  9. Renal radioisotope clearance in an unselected group of diabetics - a tool for the early recognition of diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Doschek, D.; Wulf, R.; Krause, F.J.

    1980-12-01

    Our study in unselected patients with diabetes was undertaken to determine the relation between glomerular filtration rate (GFR) and renal plasma flow (RPF) according to the patient's age. The diagnostic work-up was done with patients in unselected disease states because a classification of all systemic manifestations of the diabetes was not possible. The lack of selection may therefore reduce the value of our statistical results. From age 55 onwards, there was a reduction in GFR and, to a lesser extent, in RPF exceeding that which was age-dependent. It is, therefore, recommended to check the clearance in all patients with diabetes older than 55 years. The clearance with radioisotopically labeled substances, being a very sensitive method for the evaluation of restricted renal function, may permit an early recognition of diabetic nephropathy.

  10. Influence of amylase assay technique on renal clearance of amylase-creatinine ratio.

    Science.gov (United States)

    Levitt, M D; Johnson, S G; Ellis, C J; Engel, R R

    1977-06-01

    The influence of amylase assay technique on the renal amylase/creatinine clearance measurement was determined by analysis of serum and urine specimens obtained from 10 normal subjects. CAm/CCr averaged 2.19 +/- 0.18% with a saccharogenic technique, 1.52 +/- 0.2% with an iodometric technique, and 0.80 +/- 0.08% with a chromogenic technique. Each of these values differed significantly (P less than 0.05) from the other two. Recovery studies were carried out by adding partially purified human salivary or pancreatic amylase to human newborn serum or urine (which contain minimal endogenous amylase). Equal amylase activity was recovered from serum and urine by the saccharogenic technique whereas recovery from urine was less than 50% of that from serum using the iodometric and chromogenic techniques. The accuracy of the chromogenic technique is markedly improved by the addition of albumin to the urine assay system. Although it appears that only the saccharogenic method provides an accurate estimate of CAm/CCr, each assay technique distinguished the elevated CAm/CCr of patients with pancreatitis from the normal range established for that technique. Accurate clinical interpretation of CAm/CCr measurment requires knowledge of the amylase assay technique used.

  11. Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.

    Science.gov (United States)

    Asirvatham-Jeyaraj, Ninitha; Fiege, Jessica K; Han, Ruijun; Foss, Jason; Banek, Christopher T; Burbach, Brandon J; Razzoli, Maria; Bartolomucci, Alessandro; Shimizu, Yoji; Panoskaltsis-Mortari, Angela; Osborn, John W

    2016-10-01

    Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.

  12. Renal computed tomography with 3-dimensional angiography and simultaneous measurement of plasma contrast clearance reduce the invasiveness and cost of evaluating living renal donor candidates.

    Science.gov (United States)

    Lindgren, B W; Demos, T; Marsan, R; Posniak, H; Kostro, B; Calvert, D; Hatch, D; Flanigan, R; Steinmuller, D; Lewis, R

    1996-01-27

    Renal computed tomography (CT), 3-dimensional CT angiography (3D-CTA), and simultaneous measurement of glomerular filtration rate (GFR) by x-ray fluorescence determination of plasma contrast clearance (PCC) are alternatives to intravenous urography (IVU), renal arteriography (RA), and 24-hr urine creatinine clearance (CrCl) for evaluation of renal structure and function in living renal donor (LRD) candidates. To determine if CT, 3D-CTA, and PCC provide data comparable to IVU, RA, and CrCl, both methods were used to evaluate 23 LRD candidates. Costs were also compared. Conventional RA identified 19 accessory arteries and one case of medial fibroplasia. Each of these anomalous vessels was recognized on 3D-CTA. Venous anatomy was more clearly delineated on 3D-CTA than the venous phase of conventional RA. CT demonstrated 3 benign cysts and a single, small intraparenchymal calcification in 3 renal units. GFRs measured by PCC and CrCl were 91 +/- 4 and 132 +/- 7 ml/min/1.73m2, respectively (r = 0.64, P < 0.05). Total cost for CT/3D-CTA/PCC was 46% less than that of IVU/RA/CrCl and 40% less than RA/CrCl. CT/3D-CTA/PCC provided reliable structural and functional data at substantially less cost, discomfort, and inconvenience to the living renal donor candidate. As such, CT/3D-CTA/PCC is superior to conventional methods for evaluation of the living renal donor candidate.

  13. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  14. Clearance of glucoregulatory peptide hormones during haemodialysis and haemodiafiltration in non-diabetic end-stage renal disease patients

    DEFF Research Database (Denmark)

    Jørgensen, Morten B; Idorn, Thomas; Knop, Filip K

    2015-01-01

    was performed without concurrent dialysis treatment. Concentrations of glucose, C-peptide, insulin, glucagon, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured in plasma and dialysate. RESULTS: Ten participants completed the meal test during HD, eight completed the meal test...... with significantly higher clearance of insulin, C-peptide and GIP during HDF compared with HD. The fractional appearance of hormones entering the utilized dialysate was higher during HDF. Both dialysis modalities reduced postprandial plasma hormone concentrations in a similar manner. CONCLUSIONS: Our findings show...

  15. Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

    Science.gov (United States)

    Polidori, David C; Bergman, Richard N; Chung, Stephanie T; Sumner, Anne E

    2016-06-01

    Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance.

  16. A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin

    DEFF Research Database (Denmark)

    Hougaard Christensen, Mette Marie; Pedersen, Rasmus Steen; Stage, Tore Bjerregaard;

    2013-01-01

    The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a...

  17. Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

    Science.gov (United States)

    Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

    2008-01-01

    Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

  18. Adjusting eptifibatide doses for renal impairment: a model of dosing agreement among various methods of estimating creatinine clearance.

    Science.gov (United States)

    Healy, Martha F; Speroni, Karen Gabel; Eugenio, Kenneth R; Murphy, Patricia M

    2012-04-01

    Because of the renal elimination and increased risk for bleeding events at supratherapeutic doses of eptifibatide, the manufacturer recommends dosing adjustment in patients with renal dysfunction. Methods commonly used to estimate renal dysfunction in hospital settings may be inconsistent with those studied and recommended by the manufacturer. To compare hypothetical renal dosing adjustments of eptifibatide using both the recommended method and several other commonly used formulas for estimating kidney function. Sex, age, weight, height, serum creatinine, and estimated glomerular filtration rate (eGFR) were obtained retrospectively from the records of patients who received eptifibatide during a 12-month period. Renal dosing decisions were determined for each patient based on creatinine clearance (CrCl) estimates via the Cockcroft-Gault formula (CG) with actual body weight (ABW), ideal body weight (IBW) or adjusted weight (ADJW), and eGFR from the Modification of Diet in Renal Disease formula. Percent agreement and Cohen κ were calculated comparing dosing decisions for each formula to the standard CG-ABW. In this analysis of 179 patients, percent agreement as compared to CG-ABW varied (CG-IBW: 90.50%, CG-ADJW: 95.53%, and eGFR: 93.30%). All κ coefficients were categorized as good. In the 20% of patients receiving an adjusted dose by any of the methods, 68.6% could have received a dose different from that determined using the CG-ABW formula. In the patients with renal impairment (CrCl <50 mL/min) in this study, two thirds would have received an unnecessary 50% dose adjustment discordant from the manufacturer's recommendation. Because failure to adjust eptifibatide doses in patients with renal impairment has led to increased bleeding events, practitioners may be inclined to err on the side of caution. However, studies have shown that suboptimal doses of eptifibatide lead to suboptimal outcomes. Therefore, correct dosing of eptifibatide is important to both patient

  19. Lactate clearance is associated with mortality in septic patients with acute kidney injury requiring continuous renal replacement therapy

    Science.gov (United States)

    Passos, Rogério da Hora; Ramos, Joao Gabriel Rosa; Gobatto, André; Mendonça, Evandro José Bulhões; Miranda, Eva Alves; Dutra, Fábio Ricardo Dantas; Coelho, Maria Fernanda R; Pedroza, Andrea C; Batista, Paulo Benigno Pena; Dutra, Margarida Maria Dantas

    2016-01-01

    Abstract The aim of the study was to assess the clinical utility of lactate measured at different time points to predict mortality at 48 hours and 28 days in septic patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Consecutive critically ill patients with septic AKI requiring CRRT were prospectively studied. Variables were collected at initiation of CRRT and 24 hours later. In total, 186 patients were analyzed. Overall mortality at 48 hours was 28% and at 28 days was 69%. Initial lactate, lactate at 24 hours and the proportion of patients with a lactate clearance superior to 10% were different between survivors at 28 days [2.0 mmol/L, 1.95 mmol/L and 18/45 (40%)] and nonsurvivors [3.46 mmol, 4.66 mmol, and 18/94 (19%)]. Multivariate analysis demonstrated that lactate at 24 hours and lactate clearance, but not initial lactate, were independently associated to mortality. Area under the ROC curves for 28-day mortality was 0.635 for initial lactate; 0.828 for lactate at 24 hours and 0.701 for lactate clearance. Lactate clearance and lactate after 24 hours of CRRT, but not initial lactate, were independently associated with mortality in septic AKI patients undergoing CRRT. Serial lactate measurements may be useful prognostic markers than initial lactate in these patients. PMID:27749594

  20. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  1. Effect of prior immobilization on muscular glucose clearance in resting and running rats

    DEFF Research Database (Denmark)

    Vissing, J; Ohkuwa, T; Ploug, Thorkil

    1988-01-01

    affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated...

  2. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway.

    Science.gov (United States)

    Lo, Hsin-Yi; Ho, Tin-Yun; Li, Chia-Cheng; Chen, Jaw-Chyun; Liu, Jau-Jin; Hsiang, Chien-Yun

    2014-09-10

    Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.

  3. Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus).

    Science.gov (United States)

    Holder, Erin Hall; Citino, Scott B; Businga, Nancy; Cartier, Leslie; Brown, Scott A

    2004-06-01

    Glomerular filtration rate (GFR), renal plasma flow (RPF), and the endogenous creatinine clearance (CCr) rate were determined in 13 captive cheetahs, Acinonyx jubatus jubatus (seven females and six males, 1.5-7.5 yr of age, x = 5.02 yr), during general anesthesia with Telazol and isoflurane by measuring the urinary clearances of inulin, para-aminohipppuric acid, and endogenous creatinine, respectively. Methods to determine GFR, RPF, and endogenous CCr in captive cheetahs were evaluated, and the relationship between GFR and CCr for this species was determined. The GFR and the RPF were stable during the procedure, with mean values of 1.59+/-0.17 ml/min/kg body weight and 5.12+/-1.15 ml/min/kg body weight, respectively. Although the mean value for CCr (1.47+/-0.20 ml/min/kg body weight) was significantly less than the corresponding value for GFR, the mean difference (0.11+/-0.02 ml/min/kg weight) between the two measurements was slight, and the values were highly correlated (R2 = 0.928; P cheetahs should provide a reliable estimate of GFR, facilitating the early detection of renal disease in this species.

  4. Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

    Science.gov (United States)

    De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

    2015-11-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).

  5. The role of plasma volume, plasma renin and the sympathetic nervous system in the posture-induced decline in renal lithium clearance in man.

    Science.gov (United States)

    Smith, D F; Shimizu, M

    1978-01-01

    Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity.

  6. Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8).

    Science.gov (United States)

    Yee, Sook Wah; Nguyen, Anh Nguyet; Brown, Chaline; Savic, Radojka M; Zhang, Youcai; Castro, Richard A; Cropp, Cheryl D; Choi, Ji Ha; Singh, Diment; Tahara, Harunobu; Stocker, Sophie L; Huang, Yong; Brett, Claire M; Giacomini, Kathleen M

    2013-09-01

    Organic anion transporter 3 (OAT3, SLC22A8), a transporter expressed on the basolateral membrane of the proximal tubule, plays a critical role in the renal excretion of organic anions including many therapeutic drugs. The goal of this study was to evaluate the in vivo effects of the OAT3-Ile305Phe variant (rs11568482), present at 3.5% allele frequency in Asians, on drug disposition with a focus on cefotaxime, a cephalosporin antibiotic. In HEK293-Flp-In cells, the OAT3-Ile305Phe variant had a lower maximum cefotaxime transport activity, Vmax , [159 ± 3 nmol*(mg protein)(-1) /min (mean ± SD)] compared with the reference OAT3 [305 ± 28 nmol*(mg protein)(-1) /min, (mean ± SD), p cefotaxime renal clearance (CLR ; mean ± SD: 84.8 ± 32.1 mL/min, n = 5) compared with volunteers that were homozygous for the reference allele (158 ± 44.1 mL/min, n = 10; p = 0.006). Furthermore, the net secretory component of cefotaxime renal clearance (CLsec ) was reduced in volunteers heterozygous for the variant allele [33.3 ± 31.8 mL/min (mean ± SD)] compared with volunteers homozygous for the OAT3 reference allele [97.0 ± 42.2 mL/min (mean ± SD), p = 0.01]. In summary, our study suggests that a low-frequency reduced-function polymorphism of OAT3 associates with reduced cefotaxime CLR and CL(sec) .

  7. Determination of renal clearances of amylase/creatinine with chromogenic and enzymatic methods.

    Science.gov (United States)

    Hohenwallner, W; Wimmer, E; Sommer, R

    1979-12-01

    Urinary amylase was estimated by chromogenic (amylochrome Roche) as well as enzymatic methods (SKI and Beckman: substrate starch and substrate maltotetraose respectively). Random and timed urines (24 hour collections) were analysed. Clearances of amylase gave different results dependent upon the amylase-test used and the glomerular filtration rate. Correlation between chromogenic and enzymatic methods (starch as substrate) was poor. The ratio of amylase and creatinine clearance was used to test different methods. Reference values for this ratio for the amylochrome method (N = 106) were 2.85 +/- 0.99% and for the Beckman-DS method (N = 60) 2.82 +/- 0.87%.

  8. Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Fogh-Andersen, N; Strandgaard, S

    1996-01-01

    1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo.......3-31.0)% (P sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P

  9. Servo-control of water and sodium homeostasis during renal clearance measurements in conscious rats

    DEFF Research Database (Denmark)

    Thomsen, Klaus; Shirley, David G

    2007-01-01

    Servo-controlled fluid and sodium replacement during clearance studies is used in order to prevent loss of body fluid and sodium following diuretic/natriuretic procedures. However, even under control conditions, the use of this technique is sometimes associated with increases in proximal tubular...

  10. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance.

    NARCIS (Netherlands)

    Veldman, B.A.J.; Vervoort, G.M.M.; Blom, H.J.; Smits, P.

    2005-01-01

    INTRODUCTION: Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function.

  11. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

  12. Avaliação renal de hipertensos pela clearance de creatinina num centro de saúde de Teresina-PI, Brasil Evaluación renal de hipertensos en el aclaramiento de creatinina en un centro sanitario de Teresina- PI, Brasil Evaluation of renal hypertensive by creatinine clearance in a health center in Teresina-pi, Brazil

    Directory of Open Access Journals (Sweden)

    Dinah Sá Rezende Neta

    2012-03-01

    Full Text Available A Hipertensão Arterial Sistémica é uma das principais causas de Insuficiência Renal Crónica. Estudo de abordagem quantitativa, desenvolvido no Centro de Saúde Porto Alegre e que teve como objetivo avaliar a função renal de pacientes com hipertensão pela clearance de creatinina, a partir da mensuração da creatinina sérica. Foi realizado levantamento de dados a partir de consultas de enfermagem e solicitados exames de creatinina sérica. Após o cálculo da clearance de creatinina pela equação de Cockcroft-Gault classificou-se os pacientes em um dos seis estágios da Doença Renal Crónica. Os resultados evidenciaram que 74% da amostra apresentou lesão renal, o que mostra o quanto é importante a avaliação periódica da função renal dos pacientes com hipertensão para que possam ser acompanhados quanto a progressão da Doença Renal Crónica.Hipertensión Arterial Sistémica es una de las principales causas de Insuficiencia Renal Crónica. Por ello, este estudio tuvo por objetivo evaluar la función renal de los pacientes con hipertensión por medio del aclaramiento de creatinina, a partir de la medición de la creatinina sérica. Estudio de enfoque cuantitativo, elaborado en el Centro de Salud de Porto Alegre. La recolección de datos ocurrió en consultas de enfermería y fueron se solicitaron pruebas de la creatinina sérica. Tras realizar el cálculo del aclaramiento de la creatinina mediante la fórmula Cockcroft-Gault, los pacientes fueron clasificados en una de las seis etapas de la Enfermedad Renal Crónica. Los resultados revelaron que 74% de la muestra presentaron daño renal, lo cual demuestra cuán importante es la evaluación periódica de la función renal de los pacientes con hipertensión para que se les pueda controlada la progresión de la Enfermedad Renal Crónica.Systemic arterial hypertension is a leading cause of chronic renal failure. Thus, this study aimed at assessing the renal function of patients with

  13. Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

    Directory of Open Access Journals (Sweden)

    Eugenio Cersosimo

    2014-03-01

    Full Text Available The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2, became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation” were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

  14. [Quantification of separate renal function using Tc 99m DTPA and Tc 99m DMSA. Correlations between individual isotopic data and creatinine clearance].

    Science.gov (United States)

    Chevet, D; Moisan, A; Le Pogamp, P; Le Cloirec, J; Wehbe, B; Herry, J Y

    1984-01-01

    The purpose of this prospective study (30 controls and 100 renal patients) is to compare one to each other the values of renal function measured with: 1--the DTPA 99mTc , 2--the DMSA 99mTc , and 3--the creatinine clearance. After the control values being established, correlations are done for the whole group (n = 130) between the creatinine clearance, the DTPA 99mTc clearance and the fixation rate of the DMSA 99mTc . The correlations obtained are:--Clcr Versus Cldtpa = 0,91.--Clcr Versus % Dmsa = 0,90. - Cldtpa Versus % Dmsa = 0,93. and indicate the two isotopic tests performed give similar quantitative results than creatinine clearance. Camera and computer allow to measure the separate renal function one by one, the two isotopic test giving similar values for each kidney. The results of these studies give a good concordance with the observed diseases, except for partial renal artery stenosis. The pyelic retention of DMSA 99mTc product, in condition of ureteral compression, gives a potential overestimation of this test and is a matter to debate. The extreme simplicity and facility of DMSA 99mTc procedures make this investigation accessible to any patient and give excellent morphological and functional tests. DTPA 99mTc clearances--global and separate kidney--give a more sensitive approach than DMSA 99mTc does because vascular captation , elimination rates could be focused. DTPA 99mTc procedure is to be used in patients with transplanted kidney, silent IVP kidney, contrast media contraindication or for exploring glomerular clearance without urine collection.

  15. Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method

    DEFF Research Database (Denmark)

    Abildgaard, U; Holstein-Rathlou, N H; Leyssac, P P

    1986-01-01

    The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium...... reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional...... lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during...

  16. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Ammon Handisurya

    Full Text Available Calcineurin-inhibitors and hepatitis C virus (HCV infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR.After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92 vs. 468.80 (414.27-488.57 mL/min/m2, p = 0.005, which also resulted in significant improvements of the disposition index (p = 0.017 and adaptation index (p = 0.017 as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721, insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106 vs. 0.083 (0.054-0.144 nmol/mmol, p = 0.093 and hepatic insulin extraction (p = 0.646 remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285 or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463 were observed after the conversion of immunosuppression.HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant

  17. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.

    Science.gov (United States)

    Handisurya, Ammon; Kerscher, Corinna; Tura, Andrea; Herkner, Harald; Payer, Berit Anna; Mandorfer, Mattias; Werzowa, Johannes; Winnicki, Wolfgang; Reiberger, Thomas; Kautzky-Willer, Alexandra; Pacini, Giovanni; Säemann, Marcus; Schmidt, Alice

    2016-01-01

    Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant

  18. Avaliação renal de hipertensos pela clearance de creatinina num centro de saúde de Teresina-PI, Brasil Evaluación renal de hipertensos en el aclaramiento de creatinina en un centro sanitario de Teresina- PI, Brasil Evaluation of renal hypertensive by creatinine clearance in a health center in Teresina-pi, Brazil

    OpenAIRE

    Dinah Sá Rezende Neta; Douglas Barros Brandão; Kamila Cristiane de Oliveira Silva; Tatiana Maria Melo Guimarães dos Santos; Grazielle Roberta Freitas da Silva

    2012-01-01

    A Hipertensão Arterial Sistémica é uma das principais causas de Insuficiência Renal Crónica. Estudo de abordagem quantitativa, desenvolvido no Centro de Saúde Porto Alegre e que teve como objetivo avaliar a função renal de pacientes com hipertensão pela clearance de creatinina, a partir da mensuração da creatinina sérica. Foi realizado levantamento de dados a partir de consultas de enfermagem e solicitados exames de creatinina sérica. Após o cálculo da clearance de creatinina pela equação de ...

  19. Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Stolle, Lars B; Rawashdeh, Yazan F

    2007-01-01

    . Furthermore, we investigated regional variations in renal interstitial fluid (RIF) glucose, lactate and urea during acute UUO. MATERIAL AND METHODS: Eight anesthetized pigs were used. Microdialysis probes were inserted in the upper, middle and lower thirds of the left renal cortex and perfused with Ringer......OBJECTIVE: Acute unilateral ureteral obstruction (UUO) leads to changes in kidney function and metabolism. Microdialysis offers the possibility of topical analysis of changes in kidney metabolism. We applied microdialysis to the porcine kidney and evaluated its impact on gross kidney function......'s chloride at a rate of 0.3 microl/min. Dialysates were fractionated for 30-min periods. Bilateral intrapelvic pressure, urinary output, urinary osmolality, the excretion fractions of sodium and potassium, renal blood flow and the glomerular filtration rate were measured. Subsequently, left-sided graded...

  20. Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2

    Science.gov (United States)

    Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng

    2017-01-01

    Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation. PMID:28084414

  1. Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

    2013-12-15

    The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

  2. Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs.

    Science.gov (United States)

    Brands, Michael W; Bell, Tracy D; Rodriquez, Nancy A; Polavarapu, Praveen; Panteleyev, Dmitriy

    2009-02-01

    This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg.kg(-1).min(-1) iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging approximately 20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs.

  3. Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors

    DEFF Research Database (Denmark)

    Strandgaard, S; Kamper, A; Skaarup, P;

    1988-01-01

    1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate...

  4. MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2.

    Science.gov (United States)

    Coady, Michael J; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G; Lapointe, Jean-Yves

    2017-01-01

    The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na(+)-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17-SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na(+)/H(+) exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. Copyright © 2016 by the American Society of Nephrology.

  5. Detection of impaired renal function. Is the modern serologic marker cystatin C more accurate than the {sup 99m}Tc-MAG{sub 3} clearance?

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, M.J.; Weidling, H.; Breuel, H.P.; Biersack, H.J. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Bonn (Germany)

    2004-12-01

    Aim: Real function is usually determined by means of creatinine-clearance, and of serum Cystatin C, the latter with increasing frequency. The present study analyses, whether the diagnostic accuracy of {sup 99m}Tc-MAG{sub 3} clearance is comparable to that of these modern serologic methods. Patients, methods: 71 consecutive adult Caucasian patients (42 female, 29 male; age 50{+-}16 yrs., range 20-83) who were referred to a nuclear medicine department for determination of bilateral renal function with {sup 99m}Tc-MAG{sub 3} were included. Following sufficient hydration, 10 ml of blood were taken for determination of Cystatin C and creatinine in serum prior to i.v. injection of the radiotracer. According to the recommendations of the National Kidney Foundation, glomerular filtration rate (GFR) was calculated form serum creatinine using either Cockcroft and Gault and Modification of Diet in Renal Disease (MDRD) study equation. These estimates of GFR served as reference. Cystatin C is a low molecular protein produced by all nuclear cells and is eliminated to 85% by glomerular filtration. Analysis of {sup 99m}Tc-MAG{sub 3} clearance was performed by means of Bubeck's formula. Results: Linear regression analysis produced Pearson's correlation coefficients of r=0.68 and r=-0.69 for the comparison of either Cystatin C and {sup 99m}Tc-MAG{sub 3} clearance with the Cockcroft and Gault equation. The comparison of Cystatin C and {sup 99m}Tc-MAG{sub 3} clearance with MDRD study equation resulted in correlation coefficients of r=0.755 and r=-0.77. None of these differences were significant. The exclusion of renal impairment or the detection of an at least moderate renal impairment revealed again no significant differences between Cystatin C and {sup 99m}Tc-MAG{sub 3} clearance. Conclusions: Cystatin C and {sup 99m}Tc-MAG{sub 3} clearance are equally suited to exclude renal impairment or to detect a relevant renal impairment. Differences between both procedures are more

  6. Benefits of a continuous ambulatory peritoneal dialysis (CAPD) technique with one icodextrin-containing and two biocompatible glucose-containing dialysates for preservation of residual renal function and biocompatibility in incident CAPD patients.

    Science.gov (United States)

    Yoon, Hye Eun; Chang, Yoon Kyung; Shin, Seok Joon; Choi, Bum Soon; Kim, Byung Soo; Park, Cheol Whee; Song, Ho Cheol; Yoon, Sun Ae; Jin, Dong Chan; Kim, Yong-Soo

    2014-09-01

    In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Δ1.2 ± 2.9 mL/min/1.73 m(2), P=0.027) and urine volume (-Δ363.6 ± 543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Δ0.5 ± 2.7 mL/min/1.73 m(2), P=0.266; -Δ108.6 ± 543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, β2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549].

  7. Improved renal clearance and tumor targeting of {sup 99m}Tc-labeled anti-Tac monoclonal antibody Fab by chemical modifications

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Meyoung-kon; Jeong, Hyeh-Jean; Kao, Chih-Hao K.; Yao, Zhengsheng; Paik, David S.; Pie, Jae Eun; Kobayashi, Hisataka; Waldmann, Thomas A.; Carrasquillo, Jorge A.; Paik, Chang H. E-mail: cpaik@mail.cc.nih.gov

    2002-02-01

    This study was undertaken to improve the renal clearance and tumor targeting properties of {sup 99m}Tc-labeled humanized anti-Tac (HuTac) monoclonal antibody Fab fragments using two chemical approaches: 1) labeling with a renal secretion agent {sup 99m}Tc-mercaptoacetyltriglycine (MAG3) and 2) lowering its isoelectric point (pI) by acylation. HuTac Fab (3.3 mg/mL) was reacted with a trifluorophenyl ester (TFP) of {sup 99m}Tc-MAG3 alone or was additionally reacted with TFP-glycolate to reduce the pI. In Balb/c mice, {sup 99m}Tc-MAG3-Fab (pI>9.3) rapidly accumulated in the kidneys (177% injected dose [ID]/g at 15 min) and then gradually cleared out of the kidneys. In contrast, the glycolation (pI 4.6{approx}6.6) drastically reduced the renal uptake (31% ID/g) and also the whole-body retention (82% ID vs 101% for the nonglycolated) at 15 min, indicating that the glycolated {sup 99m}Tc-MAG3-Fab (pI 4.6{approx}6.6) was rapidly excreted. The glycolated remained in the blood longer than the nonglycolated (1.2% vs 0.3% ID/g at 360 min), but this effect was less drastic than the effect shown on the renal uptake. In nude mice bearing receptor-positive (ATAC4) tumors, the glycolated {sup 99m}Tc-MAG3-Fab increased the peak tumor uptake to 14.8% ID/g from 8.3% ID/g for {sup 99m}Tc-MAG3-Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake at 15 min. We demonstrated that the renal clearance and the tumor targeting of Fab could be optimized by chemical modifications.

  8. LP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2

    OpenAIRE

    Powell, David R.; Smith, Melinda G; Doree, Deon D; Harris, Angela L; Xiong, Wendy W; Mseeh, Faika; Wilson, Alan; Gopinathan, Suma; Diaz, Damaris; Goodwin, Nicole C.; Harrison, Bryce; Strobel, Eric; Rawlins, David B.; Carson, Ken; Zambrowicz, Brian

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to 50% of filtered glucose when SGLT2 is completely inhibited. This led us to test whether LP-925219, a small molecule dual SGLT1/SGLT2 inhibitor, increases UGE to maximal values in wild-type (WT) mice. We first tested LP-925219 inhibition of gluc...

  9. The CYP3A4*22 C>T single nucleotide polymorphism is associated with reduced midazolam and tacrolimus clearance in stable renal allograft recipients.

    Science.gov (United States)

    de Jonge, H; Elens, L; de Loor, H; van Schaik, R H; Kuypers, D R J

    2015-04-01

    Tacrolimus, a dual substrate of CYP3A4 and CYP3A5 has a narrow therapeutic index and is characterized by high between-subject variability in oral bioavailability. This study investigated the effects of the recently described CYP3A4*22 intron 6 C>T single nucleotide polymorphism on in vivo CYP3A4 activity as measured by midazolam (MDZ) clearance and tacrolimus pharmacokinetics in two cohorts of renal allograft recipients, taking into account the CYP3A5*1/*3 genotype and other determinants of drug disposition. In CYP3A5 non-expressers, the presence of one CYP3A4*22T-allele was associated with a 31.7-33.6% reduction in MDZ apparent oral clearance, reflecting reduced in vivo CYP3A4 activity. In addition, at ⩾12 months after transplantation, steady-state clearance of tacrolimus was 36.8% decreased compared with homozygous CYP3A4*22CC-wild type patients, leading to 50% lower dose requirements. Both concurrent observations in stable renal allograft recipients are consistent with a reduced in vivo CYP3A4 activity for the CYP3A4*22T-allele.

  10. Analysis of the effect of canagliflozin on renal glucose reabsorption and progression of hyperglycemia in zucker diabetic Fatty rats.

    Science.gov (United States)

    Kuriyama, Chiaki; Xu, Jun Zhi; Lee, Seunghun Paul; Qi, Jenson; Kimata, Hirotaka; Kakimoto, Tetsuhiro; Nakayama, Keiko; Watanabe, Yoshinori; Taniuchi, Nobuhiko; Hikida, Kumiko; Matsushita, Yasuaki; Arakawa, Kenji; Saito, Akira; Ueta, Kiichiro; Shiotani, Masaharu

    2014-11-01

    Sodium-glucose cotransporter 2 (SGLT2) plays a major role in renal glucose reabsorption. To analyze the potential of insulin-independent blood glucose control, the effects of the novel SGLT2 inhibitor canagliflozin on renal glucose reabsorption and the progression of hyperglycemia were analyzed in Zucker diabetic fatty (ZDF) rats. The transporter activity of recombinant human and rat SGLT2 was inhibited by canagliflozin, with 150- to 12,000-fold selectivity over other glucose transporters. Moreover, in vivo treatment with canagliflozin induced glucosuria in mice, rats, and dogs in a dose-dependent manner. It inhibited apparent glucose reabsorption by 55% in normoglycemic rats and by 94% in hyperglycemic rats. The inhibition of glucose reabsorption markedly reduced hyperglycemia in ZDF rats but did not induce hypoglycemia in normoglycemic animals. The change in urinary glucose excretion should not be used as a marker to predict the glycemic effects of this SGLT2 inhibitor. In ZDF rats, plasma glucose and HbA1c levels progressively increased with age, and pancreatic β-cell failure developed at 13 weeks of age. Treatment with canagliflozin for 8 weeks from the prediabetic stage suppressed the progression of hyperglycemia, prevented the decrease in plasma insulin levels, increased pancreatic insulin contents, and minimized the deterioration of islet structure. These results indicate that selective inhibition of SGLT2 with canagliflozin controls the progression of hyperglycemia by inhibiting renal glucose reabsorption in ZDF rats. In addition, the preservation of β-cell function suggests that canagliflozin treatment reduces glucose toxicity via an insulin-independent mechanism. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels.

  12. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer

    Science.gov (United States)

    Pal, Krishnendu; Cao, Ying; Gaisina, Irina N.; Bhattacharya, Santanu; Dutta, Shamit K.; Wang, Enfeng; Gunosewoyo, Hendra; Kozikowski, Alan P.; Billadeau, Daniel D.; Mukhopadhyay, Debabrata

    2014-01-01

    Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases including Type II diabetes, Alzheimer's disease, bipolar disorder, inflammation and cancer. Consequently it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacological and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent anti-proliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The anti-proliferative activity is most likely caused by G0–G1 and G2-M phase arrest as evident from cell cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. Additionally, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft RCC tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. PMID:24327518

  13. Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by Downregulating Klotho Gene Expression

    Directory of Open Access Journals (Sweden)

    Nuria Troyano-Suárez

    2015-01-01

    Full Text Available Cellular senescence can be prematurely induced by oxidative stress involved in aging. In this work, we were searching for novel intermediaries in oxidative stress-induced senescence, focusing our interest on integrin-linked kinase (ILK, a scaffold protein at cell-extracellular matrix (ECM adhesion sites, and on the Klotho gene. Cultured renal cells were treated with glucose oxidase (GOx for long time periods. GOx induced senescence, increasing senescence associated β-galactosidase activity and the expression of p16. In parallel, GOx increased ILK protein expression and activity. Ectopic overexpression of ILK in cells increased p16 expression, even in the absence of GOx, whereas downregulation of ILK inhibited the increase in p16 due to oxidative stress. Additionally, GOx reduced Klotho gene expression and cells overexpressing Klotho protein did not undergo senescence after GOx addition. We demonstrated a direct link between ILK and Klotho since silencing ILK expression in cells and mice increases Klotho expression and reduces p53 and p16 expression in renal cortex. In conclusion, oxidative stress induces cellular senescence in kidney cells by increasing ILK protein expression and activity, which in turn reduces Klotho expression. We hereby present ILK as a novel downregulator of Klotho gene expression.

  14. Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit.

    Science.gov (United States)

    de Jonge, Hylke; Vanhove, Thomas; de Loor, Henriëtte; Verbeke, Kristin; Kuypers, Dirk R J

    2015-09-01

    The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo. Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes. Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h(-1) at day 7; 17 ± 9.1 l h(-1) at month 12; P Cyclosporine clearance did not change over time. The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. © 2015 The British Pharmacological Society.

  15. Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

    Science.gov (United States)

    Nielsen, A H; Knudsen, F; Danielsen, H; Pedersen, E B; Fjeldborg, P; Madsen, M; Brøchner-Mortensen, J; Kornerup, H J

    1987-02-01

    In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

  16. High-performance liquid chromatography of the renal blood flow marker p-aminohippuric acid (PAH) and its metabolite N-acetyl PAH improves PAH clearance measurements.

    Science.gov (United States)

    Decosterd, L A; Karagiannis, A; Roulet, J M; Bélaz, N; Appenzeller, M; Buclin, T; Vogel, P; Biollaz, J

    1997-12-05

    PAH (N-(4-aminobenzoyl)glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction but the measurements must be corrected for the unspecific residual response observed in blank plasma. We have developed a HPLC method to specifically determine PAH and its metabolite NAc-PAH using a gradient elution ion-pair reversed-phase chromatography with UV detection at 273 and 265 nm, respectively. The separations were performed at room temperature on a ChromCart (125 mmx4 mm I.D.) Nucleosil 100-5 microm C18AB cartridge column, using a gradient elution of MeOH-buffer pH 3.9 1:99-->15:85 over 15 min. The pH 3.9 buffered aqueous solution consisted in a mixture of 375 ml sodium citrate-citric acid solution (21.01 g citric acid and 8.0 g NaOH per liter), added up with 2.7 ml H3PO4 85%, 1.0 g of sodium heptanesulfonate and completed ad 1000 ml with ultrapure water. The N-acetyltransferase activity does not seem to notably affect PAH clearances, although NAc-PAH represents 10.2+/-2.7% of PAH excreted unchanged in 12 healthy subjects. The performance of the HPLC and the colorimetric method have been compared using urine and plasma samples collected from healthy volunteers. Good correlations (r=0.94 and 0.97, for plasma and urine, respectively) are found between the results obtained with both techniques. However, the colorimetric method gives higher concentrations of PAH in urine and lower concentrations in plasma than those determined by HPLC. Hence, both renal (ClR) and systemic (Cls) clearances are systematically higher (35.1 and 17.8%, respectively) with the colorimetric method. The fraction of PAH excreted by the kidney ClR/ClS calculated from HPLC data (n=143) is, as expected, always 1). In conclusion, HPLC not only enables the simultaneous quantitation of PAH and NAc-PAH, but may also provide more

  17. Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study.

    NARCIS (Netherlands)

    Staals, L.M.; Snoeck, M.M.J.; Driessen, J.J.; Hamersvelt, H.W. van; Flockton, E.A.; Heuvel, M.W. van den; Hunter, J.M.

    2010-01-01

    BACKGROUND: Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal

  18. Targeting renal glucose reabsorption for the treatment of type 2 diabetes mellitus using the SGLT2 inhibitor dapagliflozin.

    Science.gov (United States)

    Jabbour, Serge A; Whaley, Jean M; Tirmenstein, Mark; Poucher, Simon M; Reilly, Timothy P; Boulton, David W; Saye, Joanne; List, James F; Parikh, Shamik

    2012-07-01

    Sodium-glucose co-transporter 2 (SGLT2) plays a key role in glucose homeostasis as the key transporter responsible for most renal glucose reabsorption in the proximal tubules of the kidney. Dapagliflozin is a potent, selective, and reversible inhibitor of SGLT2 that lowers blood glucose levels in an insulin-independent fashion. This novel agent has been studied extensively in patients with type 2 diabetes mellitus (T2DM). In these clinical trials, dapagliflozin significantly decreased glycated hemoglobin and fasting plasma glucose levels when administered alone or as add-on treatment in patients who were already receiving metformin, a sulfonylurea (glimepiride), pioglitazone, or insulin. Moreover, dapagliflozin decreased body weight when taken as monotherapy or in combination with metformin, a sulfonylurea, or insulin, and mitigated weight gain in patients receiving pioglitazone. Consistent with preclinical toxicology studies, dapagliflozin has a manageable adverse event profile that is largely predictable from its mechanism of action. While there are no clinically significant negative effects on renal function or electrolytes, dapagliflozin treatment is associated with increased frequencies of urinary tract infections and vulvovaginitis/balanitis. With a mechanism of action that is distinct from and complementary to that of existing antihyperglycemic therapies, dapagliflozin is an effective antihyperglycemic agent that is well tolerated and may enhance weight loss. As such, dapagliflozin promises to become an important adjunctive therapy for comprehensive treatment of T2DM.

  19. PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity.

    Science.gov (United States)

    Benincasa, Monica; Zahariev, Sotir; Pelillo, Chiara; Milan, Annalisa; Gennaro, Renato; Scocchi, Marco

    2015-05-05

    The proline-rich antibacterial peptide Bac7(1-35) protects mice against Salmonella typhimurium infection, despite its rapid clearance. To overcome this problem the peptide was linked to a polyethylene glycol (PEG) molecule either via a cleavable ester bond or via a non-hydrolysable amide bond. Both the PEGylated conjugates retained most of the in vitro activity against S. typhimurium. In addition, the ester bond was cleaved in human serum or plasma, releasing a carboxymethyl derivative of Bac7(1-35) which accounts for a higher activity of this peptide with relative to the other, non-hydrolysable form. Both PEGylated peptides maintained the capacity of the unconjugated form to kill bacteria without permeabilizing the bacterial membranes, by penetrating into cells. They exploited the same transporter as unmodified Bac7(1-35), suggesting it has the capacity to internalize quite sizeable cargo if this is linked to Bac7 fragment. PEGylation allows the peptide to have a wide distribution in mice, and a slow renal clearance, indicating that this strategy would improve the bioavailability of Bac7, and in principle of other antimicrobial peptides. This can be an equally important issue to reducing cytotoxicity for therapeutic use of these antibacterials.

  20. Effect of intravenous glucose infusion on renal function in normal man and in insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Frandsen, M; Parving, H H; Christiansen, JS

    1981-01-01

    -controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7 +/- 0.1 to 10.9 +/- 0.4 mmol/l (SEM) (p less than or equal to 0.01). Glomerular filtration rate increased from 116 +/- 2 to 123 +/- 3 ml/mi x 1.73 m2 (p less than or equal to 0.01), while...... no change in renal plasma flow was seen - 552 +/- 11 versus 553 +/- 18 ml/min x 1.73 m2. Volume expansion with intravenous saline infusion in six of the normal subjects induced no changes in blood glucose or kidney function. In seven strictly controlled insulin-dependent diabetics, blood glucose values were...... raised from 4.6 +/- 0.4 to 16.0 +/- 0.6 mmol/l and clamped by means of an 'artificial beta cell'. Glomerular filtration rate increased in all patients, from 133 +/- 5 to 140 +/- 6 ml/min x 1.73 m2 (p less than or equal to 0.02), as did renal plasma flow from 576 +/- 26 to 623 +/- 38 ml/min x 1.73 m2 (p...

  1. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

    Science.gov (United States)

    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy.

  2. Caffeine renal clearance and urine caffeine concentrations during steady state dosing. Implications for monitoring caffeine intake during sports events.

    OpenAIRE

    Birkett, D J; Miners, J O

    1991-01-01

    1. Relationships between the plasma and urine concentrations and clearances of caffeine over successive dosage intervals at steady-state were investigated in six healthy volunteers administered caffeine, 150 mg 8 hourly for 6 days. 2. There was marked inter-individual variability in the urine (15.9-fold range) and steady-state plasma (8.1-fold range) concentrations of caffeine. 3. Urine caffeine concentrations were similar to those in plasma, with mean ratios (plasma:urine) ranging from 1.10 ...

  3. The association of early combined lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients.

    Science.gov (United States)

    Freire Jorge, Pedro; Wieringa, Nienke; de Felice, Eva; van der Horst, Iwan C C; Oude Lansink, Annemieke; Nijsten, Maarten W

    2017-08-21

    The development of renal and liver dysfunction may be accompanied by initially subtle derangements in the gluconeogenetic function. Discrepantly low glucose levels combined with high lactate levels might indicate an impaired Cori cycle. Our objective was to examine the relation between early lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients. Over a 4-year period (2011 to 2014), all adult patients admitted to our adult 48-bed teaching hospital intensive care unit (ICU) for at least 12 h were retrospectively analyzed. Lactate and glucose were regularly measured with point-of-care analyzers in all ICU patients. Lactate and glucose measurements were collected from 6 h before to 24 h after ICU admission. Patients with fewer than four lactate/glucose measurements were excluded. Patients received insulin according to a computer-guided control algorithm that aimed at a glucose level 2.3 mmol/L) and glucose quintiles (≤7.0; 7.0-7.6; 7.6-8.2; 8.2-9.0; >9.0 mmol/L) were related with outcome in univariate analysis (p < 0.001). Acute Physiology and Chronic Health Evaluation (APACHE) IV, lactate, and glucose were associated with renal and liver dysfunction in multivariate analysis (p < 0.001), with a U-shaped relationship for glucose. The combination of the highest lactate quintile with the lowest glucose quintile was associated with the highest rates of renal dysfunction, liver dysfunction, and mortality (p < 0.001) with a significant interaction between lactate and glucose (p ≤ 0.001). Abnormal combined lactate and glucose measurements may provide an early indication of organ dysfunction. In critically ill patients a 'normal' glucose with an elevated lactate should not be considered desirable, as this combination is related with increased mortality.

  4. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    Directory of Open Access Journals (Sweden)

    Mizerski Grzegorz

    2015-09-01

    Full Text Available The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1, and sodium-glucose co-transporter type type 2 (SGLT2 - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin, where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect, and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.

  5. Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Danielsen, H; Knudsen, F; Nielsen, A H; Jensen, T; Kornerup, H J; Madsen, M

    1986-09-01

    Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

  6. Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production

    DEFF Research Database (Denmark)

    Krag, Søren; Nyengaard, Jens R; Wogensen, Lise

    2007-01-01

    BACKGROUND: There is a correlation between renal graft rejection and blood glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic renal diseases, which in some circumstances progress rapidly. Since transforming growth factor-beta1 (TGF-beta) levels are elevated in many renal...... diseases, the accelerated progression may be due to interactions between glucose and locally produced TGF-beta1. Therefore, we investigated the effect of mild hyperglycaemia on glomerular morphology and collagen production in TGF-beta1 transgenic mice. METHODS: To achieve BG concentrations of approximately...... is involved. This emphasizes the importance of strict BG control in renal transplant patients and diabetic patients with renal malfunctions unrelated to diabetes. Udgivelsesdato: 2007-Sep...

  7. Effect of HLA on hepatitis C virus clearance and persistence in anti-HCV-positive end-stage renal disease patients

    Directory of Open Access Journals (Sweden)

    Serkan Ocal

    2014-01-01

    Full Text Available Background/Aims: The efficacy of immune response against hepatitis C virus (HCV is determined by human leukocyte antigen (HLA molecules of the host which present HCV antigens to CD4 + and CD8 + T lymphocytes. In this study, we aimed to investigate the possible relationship between the frequencies of certain HLA class I-II alleles and the natural history of HCV in patients with end-stage renal disease (ESRD. Settings and Design: This is a retrospective cohort study conducted in a university hospital. Patients and Methods: The present study comprised 189 ESRD patients (candidates for renal transplantation who had positive anti-HCV antibody test. The results concerning HCV and HLA status were gathered from patients′ files. The viral persistence was compared between the groups that were determined by HLA sub-typing. Statistical Analysis: Statistical evaluation was performed using Mann-Whitney U-test, Chi-square test, and Fisher′s exact test. Level of error was set at 0.05 for all statistical evaluations, and P values < 0.05 were considered statistically significant. Results: We found possible association between the course of HCV infection and specific HLA alleles. HLA class I CwFNx016 and HLA class II DRBFNx0110 alleles were observed more frequently in the viral clearance group (P < 0.05. The HLA class I BFNx0138 allele group was more prone to develop chronic hepatitis C (P < 0.01. Conclusions: These findings suggest that HLA class I CwFNx016 and HLA class II DRBFNx0110 alleles may be associated with immunological elimination of HCV in Turkish patients on hemodialysis. HLA sub-typing could help predict the prognosis of HCV infection.

  8. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  9. Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models

    Science.gov (United States)

    Liang, Yin; Arakawa, Kenji; Ueta, Kiichiro; Matsushita, Yasuaki; Kuriyama, Chiaki; Martin, Tonya; Du, Fuyong; Liu, Yi; Xu, June; Conway, Bruce; Conway, Jamie; Polidori, David; Ways, Kirk; Demarest, Keith

    2012-01-01

    Background Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). Methods 14C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Results Treatment with canagliflozin 1 mg/kg lowered RTG from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. Conclusions Canagliflozin lowered RTG and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity. PMID:22355316

  10. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models.

    Directory of Open Access Journals (Sweden)

    Yin Liang

    Full Text Available BACKGROUND: Canagliflozin is a sodium glucose co-transporter (SGLT 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM. METHODS: (14C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE at different blood glucose (BG concentrations and the renal threshold for glucose excretion (RT(G in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. RESULTS: Treatment with canagliflozin 1 mg/kg lowered RT(G from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RT(G. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. CONCLUSIONS: Canagliflozin lowered RT(G and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity.

  11. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models.

    Science.gov (United States)

    Liang, Yin; Arakawa, Kenji; Ueta, Kiichiro; Matsushita, Yasuaki; Kuriyama, Chiaki; Martin, Tonya; Du, Fuyong; Liu, Yi; Xu, June; Conway, Bruce; Conway, Jamie; Polidori, David; Ways, Kirk; Demarest, Keith

    2012-01-01

    Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). (14)C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3)H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RT(G)) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Treatment with canagliflozin 1 mg/kg lowered RT(G) from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RT(G). Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. Canagliflozin lowered RT(G) and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity.

  12. Effect of intravenous glucose infusion on renal function in normal man and in insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Frandsen, M; Parving, H H; Christiansen, JS

    1981-01-01

    The effect of intravenous glucose infusion on glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) and on urinary excretion of albumin and beta-2-microglobulin were studied in ten normal subjects and seven metabolically well...... less than or equal to 0.02). Urinary albumin excretion remained unchanged in both normal subjects and diabetics. beta-2-microglobulin excretion rate increased significantly in the diabetics following glucose infusion, while no significant change was seen in the normal subjects. Our results show......-controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7 +/- 0.1 to 10.9 +/- 0.4 mmol/l (SEM) (p less than or equal to 0.01). Glomerular filtration rate increased from 116 +/- 2 to 123 +/- 3 ml/mi x 1.73 m2 (p less than or equal to 0.01), while...

  13. Effects of sodium bicarbonate and ammonium chloride pre-treatments on PEPT2 (SLC15A2) mediated renal clearance of cephalexin in healthy subjects.

    Science.gov (United States)

    Liu, Rui; Tang, Audrey May Yi; Tan, Yen Ling; Limenta, Lie Michael George; Lee, Edmund Jon Deoon

    2011-01-01

    PEPT2 mediates the H(+) gradient-driving reabsorption of di- and tri-peptides, and various peptidomimetic compounds in the kidney. This study examines the influence of urinary pH modification through sodium bicarbonate and ammonium chloride pre-treatments on the function of PEPT2 in healthy subjects, using cephalexin as the probe drug. Sixteen male subjects received a single oral dose of 1000 mg cephalexin under ammonium chloride and sodium bicarbonate treatment, respectively, with a wash-out period of one week. The study subjects were genotyped for PEPT2 polymorphic variants. Cephalexin concentrations in plasma and urine were determined by high performance liquid chromatography. The mean renal clearance of cephalexin was significantly higher under ammonium chloride treatment than that under sodium bicarbonate treatment (P < 0.01). This difference was significant for PEPT2*2/*2 (P = 0.017) but not for PEPT2*1/*1 (P = 0.128). No differences were observed for other pharmacokinetic parameters. The findings of this study suggest that urinary pH changes may alter the pharmacokinetics of PEPT2's substrates. This effect was more obvious for the PEPT2*2/*2.

  14. Impaired Fasting Glucose and Diabetes as Predictors for Radial Artery Calcification in End Stage Renal Disease Patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Janda

    2013-01-01

    Full Text Available Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis. The examined parameters included common carotid artery intima-media thickness (CCA-IMT, BMI, incidence of diabetes and impaired fasting glucose (IFG, dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA, osteopontin (OPN, osteoprotegerin (OPG, and osteocalcin (OC were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P=0.0004 and older age (P=0.003, as well as higher OPG (P=0.014 and ADMA concentrations (P=0.022. Fasting glucose >5.6 mmol/l (IFG and diabetes significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P=0.006 and mortality (P=0.004; OR for death 5.39 [1.20–24.1] after adjustment for dialysis status and age. Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death.

  15. Renal Safety of Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Desai, Mehul; Yavin, Yshai; Balis, Dainius; Sun, Don; Xie, John; Canovatchel, William; Rosenthal, Norm

    2017-01-12

    The incidence of renal-related adverse events (AEs) with canagliflozin in patients with type 2 diabetes mellitus from a pooled population of patients in 7 active- and placebo-controlled trials (N = 5,598) and in a 104-week study versus glimepiride (N = 1,450) was low and similar in canagliflozin and non-canagliflozin groups. In the study versus glimepiride, canagliflozin was associated with an initial acute decrease in estimated glomerular filtration rate (eGFR) that attenuated over time, while eGFR declined progressively over 104 weeks with glimepiride; the incidence of renal-related AEs with canagliflozin was generally stable over time, while the incidence with glimepiride increased over 104 weeks. In the analysis reported in this manuscript based on postmarketing reports from the US Food and Drug Administration Adverse Event Reporting System, a potential signal was identified for acute kidney injury with all approved sodium glucose co-transporter 2 (SGLT2) inhibitors (ie, canagliflozin, dapagliflozin, empagliflozin). The early onset of acute kidney injury events with SGLT2 inhibitors in postmarketing reports likely reflects the acute changes in eGFR due to the known renal haemodynamic effects of SGLT2 inhibition.

  16. Radionuclide Renal Dynamic Imaging GFR (glomerular filtration rate) to Evaluate Renal Function and Serum Creatinine (Scre) Evaluation Comparison of Renal Clearance%核素肾动态显像GFR测定与肌酐清除率评价肾功能的相关性比较

    Institute of Scientific and Technical Information of China (English)

    张晓; 孙莲华

    2014-01-01

    Objective:To study radionuclide renal dynamic imaging GFR ( glomerular filtration rate ) to evaluate renal function and se-rum creatinine ( Scre) evaluation comparison of renal clearance .Methods:First estimation of normal reference value of my GFR in the control group;when renal function damage of 80 cases, measurement of GFR and creatinine clearance rate comparison of measurement val-ues.Results:80 cases patients of GFR and muscle anhydride cleared rate contrast , GFR and serum muscle anhydride are exception who 63 cases, its GFR value 81.3 ±12.8ml/min and muscle anhydride cleared rate 85.5 ±11.3ml/min, differences no significantly sexual meaning (P>0.05);12 cases chronic kidney damage patients , muscle anhydride cleared rate 70.1 ±8.3ml/min,GFR value 50.2 ± 6.8ml/min, differences has significantly sexual meaning ( P<0.01); Value of 5 patients with severe hydronephrosis GFR 19.1 ±7. 3ml/min, 23.6 ±5.8ml/min creatinine clearance rate, the difference has a significant meaning (P<0.01).Radionuclide renal dynam-ic values of GFR and creatinine clearance rate more in line with;early GFR and impaired renal function creatinine clearance rate of earlier abnormal changes .Conclusion:Radionuclide renal dynamic checking GFR determination can better reflect the change rate of Glomerular filtration function in early stage , a more accurate estimation of renal function .%目的:探讨放射性核素肾动态显像GFR(肾小球滤过率)评价肾功能与血清肌酐( Scre)清除率评价肾功能的比较。方法:首先对照组估算我科GFR的正常参考值;80例当肾功能受损害时,GFR的测量值与血清肌酐清除率测定值的比较。结果:80例患者的GFR与肌酐清除率对比,GFR和血清肌酐均异常者63例,其GFR值81.3±12.8ml/min与肌酐清除率85.5±11.3ml/min,差异无显著性意义(P>0.05);12例慢性肾损害患者,肌酐清除率70.1±8.3ml/min,GFR值50.2±6.8ml

  17. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans.

    Science.gov (United States)

    Lu, Yasong; Griffen, Steven C; Boulton, David W; Leil, Tarek A

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80%) of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al., 2013), and evaluated against clinical data from the literature (Mogensen, 1971; Wolf et al., 2009; Polidori et al., 2013). The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to SGLT1/2 modulation.

  18. Lower metabolic clearance of tizanidine in Japanese subjects.

    Science.gov (United States)

    Momo, Kenji; Homma, Masato; Kohda, Yukinao

    2013-12-01

    Our aim was to determine whether metabolic clearance, renal clearance, or both elimination pathways contribute to ethnic differences in tizanidine clearance, which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic parameters of tizanidine in 9 healthy male Japanese subjects were compared with those of Caucasians in previous studies. Metabolic clearance of tizanidine was lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg), although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The results suggest that ethnic differences in tizanidine clearance are due to differences in metabolic clearance.

  19. The protective effects of beta-casomorphin-7 against glucose -induced renal oxidative stress in vivo and vitro.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The present study aimed to investigate the effect of β-casomorphin-7 (BCM7 on the oxidative stress occurring in kidney tissue in streptozotocin (STZ-induced diabetic rats and proximal tubular epithelial cells (NRK-52E exposure to high glucose (HG by using biochemical methods. There is a significant decrease in plasma insulin and a significant increase in plasma glucagon in the rats of diabetic group. Oral administration of BCM7 for 30 days to rats with STZ-induced diabetes resulted in a significant increase in serum level of insulin, and a decrease in the level of glucagon. Moreover, rats with STZ-induced diabetes had lower levels of superoxide dismutase (SOD, glutathione peroxidase (GPx and total antioxidative capacity (T-AOC, higher levels of malondialdehyde (MDA and hydrogen peroxide (H2O2 in the kidney than that in the control rats. The administration of BCM7 altered the changes of SOD, GPx, T-AOC, MDA and H2O2 in the kidney of diabetic rats. Furthermore, BCM7 alleviated high glucose-induced decreasement in SOD and GPx activity, increasement in MDA contents in the NRK-52E cells. BCM7 ameliorated the changes of angiotensin converting enzyme (ACE and ACE2 levels in the kidney of diabetic rats and BCM7 lowered the levels of angiotensin (AngII in the kidney of diabetic rats and culture medium for cells. Moreover losartan (antagonist of angiotensin II type I receptor lowered the high glucose-induced oxidative stress in the NRK-52E cells. Our results suggest that administration of BCM7 would alleviate high glucose-induced renal oxidative stress in vivo and in vitro, which may be associated with down regulation of the concentration of Ang II partly.

  20. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  1. Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance

    DEFF Research Database (Denmark)

    Jødal, Lars; Brøchner-Mortensen, Jens

    2009-01-01

    and adults. Material and methods. Cl was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma concentration curve followed for 4-5 h after injection of 51Cr-EDTA (range of clearance: 8-183 mL/min/1.73 m²). Plasma volume, PV and the "missing" area under the plasma fraction curve......Background. Total plasma clearance of 51Cr-EDTA, Cl, is widely used as a measure of GFR. Commonly, only the final part of the plasma concentration curve is measured, and a one-pool clearance (slope-intercept clearance), Cl1, is computed. Empirically determined second-order polynomials......, a (minutes), not used for determination of Cl1, were measured. Results. The true relationship between Cl and Cl1 is given by Cl = Cl1/(1+f·Cl1), where f = a/PV. For men, women and children alike, the equation f = 0.0032·BSA-1.3 was applicable (BSA = body surface area in m²). Estimation errors on clearance...

  2. Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule.

    Science.gov (United States)

    Ghezzi, Chiara; Yu, Amy S; Hirayama, Bruce A; Kepe, Vladimir; Liu, Jie; Scafoglio, Claudio; Powell, David R; Huang, Sung-Cheng; Satyamurthy, Nagichettiar; Barrio, Jorge R; Wright, Ernest M

    2017-03-01

    Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs. Copyright © 2017 by the American Society of Nephrology.

  3. Physiologically based pharmacokinetic-pharmacodynamic modeling to predict concentrations and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules.

    Science.gov (United States)

    Mori, Kazumi; Saito, Ryuta; Nakamaru, Yoshinobu; Shimizu, Makiko; Yamazaki, Hiroshi

    2016-11-01

    Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%-60% after the oral administration of clinical doses (100-300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%-0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin-treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Mucociliary clearance

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Mortensen, Jann

    2014-01-01

    Mucociliary clearance has long been known to be a significant innate defence mechanism against inhaled microbes and irritants. Important knowledge has been gathered regarding the anatomy and physiology of this system, and in recent years, extensive studies of the pathophysiology related to lung...... pharmacological interventions on clearance rate, to study the importance of defective mucus clearance in different lung diseases or as a diagnostic tool in the work-up of patients with recurrent airway diseases. The aim of this review is to provide an overview of the anatomy, physiology, pathophysiology...

  5. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P oral (Cau r = -0.61, P indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.

  6. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial.

    Science.gov (United States)

    Stein, Peter; Berg, Jolene K; Morrow, Linda; Polidori, David; Artis, Eunice; Rusch, Sarah; Vaccaro, Nicole; Devineni, Damayanthi

    2014-10-01

    Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin. Patients (N=37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B-D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period. A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B-D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC0-2h, -7.5% for B vs A; -18.5% for C vs A; -12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC0-2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated. These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Plasma Creatinine Clearance in the Dog

    Science.gov (United States)

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  8. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    Directory of Open Access Journals (Sweden)

    Yasong eLu

    2014-12-01

    Full Text Available In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1 and 2 (SGLT2 along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80% of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al. data (2013, and evaluated against clinical data from the literature (Mogensen, 1971;Wolf et al., 2009;Polidori et al., 2013. The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to

  9. Lower blood glucose and variability are associated with earlier recovery from renal injury caused by episodic urinary tract infection in advanced type 2 diabetic chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Ping-Fang Chiu

    Full Text Available In our previous study, type 2 diabetic chronic kidney disease (CKD patients with glomerular filtration rates of 9 days, Group B groups. The differences in the continuous and categorical variables of the two groups were assessed separately. The mean glucose levels and their variability (using the standard deviation and the coefficient of standard deviation were compared at the fasting, midday pre-meal, evening pre-meal, and evening post-meal time points during hospitalization. We have organized the manuscript in a manner compliant with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology statement.Acute kidney injury occurred within the two groups (p = 0.007 and p = 0.001, respectively. The early-morning blood glucose levels (149.7±44.0 mg/dL and average blood glucose levels (185.6±52.0 mg/dL were better in Group A (p = 0.01, p = 0.02. Group A patients also had lower glucose variability than Group B at the different time points (p<0.05. Group A also had earlier renal recovery. More relevant pathogens were identified from blood in Group B (p = 0.038.Early-morning fasting and mean blood glucose levels and their variability can be good indicators of severe infection and predictors of renal outcome in type 2 diabetic patients with CKD and UTI.

  10. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  11. Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor.

    OpenAIRE

    Phillips, A.O.; Steadman, R.; Topley, N; Williams, J. D.

    1995-01-01

    Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in...

  12. Validation of a Novel Method for Determining the Renal Threshold for Glucose Excretion in Untreated and Canagliflozin-treated Subjects With Type 2 Diabetes Mellitus

    OpenAIRE

    Polidori, David; Sha, Sue; Ghosh, Atalanta; Plum-Mörschel, Leona; Heise, Tim; Rothenberg, Paul

    2013-01-01

    Context: The stepwise hyperglycemic clamp procedure (SHCP) is the gold standard for measuring the renal threshold for glucose excretion (RTG), but its use is limited to small studies in specialized laboratories. Objective: The objective of the study was to validate a new method for determining RTG using data obtained during a mixed-meal tolerance test (MMTT) in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus (T2DM). Design: This was an open-label study with 2 sequen...

  13. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Qilu [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zhao, Leping [Department of Pharmacy, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi; Zhang, Yali [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Zhaoyu [Department of International High School, Shanghai Jiaotong University Nanyang Affiliated (Kunshan) School, Minhang District, Shanghai (China); Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Dan, E-mail: yqyyld@163.com [Department of Nephrology, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

  14. STANDARDIZATION OF AN IN VITRO MODEL OF DIABETIC NEPHROPATHY IN RENAL TUBULAR CELLS AND INVESTIGATION OF THE ROLE OF ALDOSE REDUCTASE PATHWAY IN HIGH GLUCOSE-INDUCED RENAL CELL INJURY

    OpenAIRE

    El Gamal, Heba

    2015-01-01

    Diabetic nephropathy (DN) is the leading cause of end stage renal disease, and one of the most serious microvascular complications of diabetes mellitus. Increase in the shift of glucose into the aldose reductase pathway during diabetes leads to accumulation of sorbitol and fructose in the cells, and causes an imbalance in the associated cofactors, which in turn cause deleterious events such as oxidative stress, endoplasmic reticulum (ER) stress and cell death in the kidney. The objective of t...

  15. Impact of radical nephrectomy on renal functional outcome in patients with no other co-morbidity as determined by 24-h urinary creatinine clearance

    Directory of Open Access Journals (Sweden)

    H.H. Qureshi

    2015-12-01

    Conclusion: The results from this study show that RN is associated with a decrease in CrCl in one third of the study population. Therefore it is recommended that patients undergoing RN should be strictly monitored for occult renal failure and managed promptly to prevent serious morbidity of frank renal failure.

  16. Studies of renal injury. II. Activation of the glucose transporter 1 (GLUT1) gene and glycolysis in LLC-PK1 cells under Ca2+ stress.

    Science.gov (United States)

    Dominguez, J H; Song, B; Liu-Chen, S; Qulali, M; Howard, R; Lee, C H; McAteer, J

    1996-01-01

    Injury to the renal proximal tubule is common and may be followed by either recovery or cell death. The survival of injured cells is supported by a transient change in cellular metabolism that maintains life even when oxygen tension is reduced. This adaptive process involves the activation of the gene encoding the glucose transporter GLUT1, which is essential to maintain the high rates of glucose influx demanded by glycolysis. We hypothesized that after cell injury increases of cell Ca2+ (Ca2+i) initiate the flow of information that culminates with the upregulation of the stress response gene GLUT1. We found that elevations of Ca2+i caused by the calcium ionophore A23187 activated the expression of the GLUT1 gene in LLC-PK1 cells. The stimulatory effect of Ca2+i on GLUT1 gene expression was, at least in part, transcriptional and resulted in higher levels of GLUT1 mRNA, cognate protein, cellular hexose transport activity, glucose consumption, and lactate production. This response was vital to the renal cells, as its interruption severely increased Ca2+-induced cytotoxicity and cell mortality. We propose that increases of Ca2+i initiate stress responses, represented in part by activation of the GLUT1 gene, and that disruption to the flow of information originating from Ca2+-induced stress, or to the coordinated expression of the stress response, prevents cell recovery after injury and may be an important cause of permanent renal cell injury and cell death. PMID:8755650

  17. Renal transepithelial transport of nucleosides.

    Science.gov (United States)

    Nelson, J A; Vidale, E; Enigbokan, M

    1988-01-01

    Previous work from this and other laboratories has suggested that the mammalian kidney has unique mechanisms for handling purine nucleosides. For example, in humans and in mice, adenosine undergoes net renal reabsorption whereas deoxyadenosine is secreted [Kuttesch and Nelson: Cancer Chemother. Pharmacol. 8, 221 (1982)]. The relationships between these renal transport systems and classical renal organic cation and anion, carbohydrate, and cell membrane nucleoside transport carriers are not established. To investigate possible relationships between such carriers, we have tested effects of selected classical transport inhibitors on the renal clearances of adenosine, deoxyadenosine, 5'-deoxy-5-fluorouridine (5'-dFUR), and 5-fluorouracil in mice. The secretion of deoxyadenosine and 5'-dFUR, but not the reabsorption of adenosine or 5-fluorouracil, was prevented by the classical nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Cimetidine, an inhibitor of the organic cation secretory system, also inhibited the secretion of 5'-dFUR, although it did not inhibit deoxyadenosine secretion in earlier studies [Nelson et al.: Biochem. Pharmacol. 32, 2323 (1983)]. The specific inhibitor of glucose renal reabsorption, phloridzin, failed to inhibit the reabsorption of adenosine or the secretion of deoxyadenosine. Failure of the nucleoside transport inhibitors and phloridzin to prevent adenosine reabsorption suggests that adenosine reabsorption may occur via a unique process. On the other hand, inhibition of the net secretion of deoxyadenosine and 5'-dFUR by dipyridamole and nitrobenzylthioinosine implies a role for the carrier that is sensitive to these compounds in the renal secretion (active transport) of these nucleosides.

  18. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were m...

  19. Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells.

    Science.gov (United States)

    Lee, Hak Joo; Mariappan, Meenalakshmi M; Feliers, Denis; Cavaglieri, Rita C; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S

    2012-02-10

    Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High glucose stimulation of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. High glucose activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase phosphorylation, and dephosphorylation of eEF2; these events were inhibited by NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA translation as well as global and matrix protein synthesis. NaHS induction of AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase β, but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase β inhibitor, had the same effect. Renal cortical content of cystathionine β-synthase and cystathionine γ-lyase, hydrogen sulfide-generating enzymes, was significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly identified modulator of protein synthesis in the kidney, and reduction in its generation may contribute to kidney injury in diabetes.

  20. Metal-activated C-peptide Facilitates Glucose Clearance and the Release of a Nitric Oxide Stimulus via the GLUT1 Transporter

    Science.gov (United States)

    Meyer, Jennifer A.; Froelich, Jennifer M.; Reid, Gavin E.; Karunarathne, Welivitya K.A.; Spence, Dana M.

    2008-01-01

    Objective: Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and improving blood flow. We hypothesized that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus of nitric oxide production. Research Design and Methods: Erythrocytes obtained from rabbits (n=11) and humans (healthy and those with type 2 diabetes, n=7) were incubated with C-peptide (in the absence and presence of Fe (II) and Cr (III)) and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of the glucose transporter GLUT1, and mannose, a glycolysis inhibitor. To determine glucose transport, 14C-labelled glucose was added to erythrocytes in the presence and absence of the C- peptide/metal complex and the aforementioned inhibitors. Results: The release of ATP from the erythrocytes of patients with diabetes increased from 64 nmol/l (± 13 nmol/l) to 260 nmol/l (± 39 nmol/l) upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe (II), which was extended upon binding to Cr (III). The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr (III), the amount of glucose transferred into the erythrocyte increased by 31%. Conclusions: When complexed to Fe (II) or Cr (III), C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through the GLUT1 transporter. PMID:17965850

  1. Vildagliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in Zucker Diabetic Fatty rat

    NARCIS (Netherlands)

    Vavrinec, Peter; Henning, Robert H.; Landheer, Sjoerd W.; Wang, Yumei; Deelman, Leo E.; van Dokkum, Richard P. E.; Buikema, Hendrik

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is associated with risk for chronic kidney disease (CKD), which is associated with a decrease in renal myogenic tone - part of renal autoregulatory mechanisms. Novel class of drugs used for the treatment of T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitors, have protect

  2. Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Ramiro; A; Sanchez; Hugo; Sanabria; Cecilia; de; los; Santos; Agustin; J; Ramirez

    2015-01-01

    Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the

  3. Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    Directory of Open Access Journals (Sweden)

    Anna Alice Rolim Chaves

    2010-01-01

    Full Text Available INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21 and without renal artery stenosis, (n=20. In vitro glomerular filtration rate analysis (51Cr-EDTA and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m² in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m² in the group without renal artery stenosis (p=0.04. Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m², p=0.001 and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m², p=0.68. Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA did not show

  4. Glomerular Filtration Rate Measured by 51Cr-EDTA Clearance: Evaluation of Captopril-Induced Changes in Hypertensive Patients with and without Renal Artery Stenosis

    Science.gov (United States)

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

    2010-01-01

    INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m2 in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/ kg/1.73m2, p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m2, p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant

  5. Glomerular filtration rate measured by {sup 51}Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit, E-mail: annaalice100@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

    2010-07-01

    Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ({sup 51}Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using {sup 51}Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ({sup 51}Cr-EDTA) and {sup 99m}Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6+-21.8 ml/kg/1.73 m{sup 2} in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1+-28.7 ml/kg/1.73m{sup 2} in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+-14.8 ml/kg/1.73m{sup 2}, p=0.001) and an insignificant change in the group without RAS (to 62.2+-23.6 ml/kg/1.73m{sup 2}, p=0.68). Scintigraphy with technetium-99m dimercapto

  6. Biological evaluation of two iodine-123-labeled D-glucose acetals prepared as glucose transporter radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Brunet-Desruet, Marie-Dominique; Ghezzi, Catherine; Morin, Christophe; Comet, Michel; Fagret, Daniel

    1998-07-01

    Two iodinated acetals of D-glucose, 4,6-(R)-O-(2'-iodoethylidene)-{alpha}, {beta}-D-glucose and 4,6-(R)-O-(4'-iodobenzylidene)-{alpha}, {beta}-D-glucose , were prepared and their potential as suitable SPECT radioligands for imaging of glucose transporters was studied. Both are analogs of acetal D-glucose derivatives, which are known to bind to the exofacial sites of the glucose transport protein (GluT). To assess whether iodinated acetals 1 and 2 interacted with the glucose transporter, they were tested in vitro in human erythrocytes (GluT1) and neonatal rat cardiomyocytes (GluT4). The results indicated that 1 and 2 had a very low affinity for the glucose transporter and probably accumulated in cells. Study of their tissue distribution was carried out in the mouse in vivo: Both compounds showed fast tissue clearance with preferential renal elimination. It is concluded that iodinated acetals of D-glucose 1 and 2 are not suitable for GluT targeting in vivo.

  7. AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xia Luo

    2015-01-01

    Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

  8. Evaluation of the efficacy of tamsulosin with or without deflazacort for stone clearance after extracorporeal shockwave lithotripsy for upper ureteral and renal calculi

    Directory of Open Access Journals (Sweden)

    Rajeev T. P.

    2016-02-01

    Conclusions: Addition of alpha-blocker tamsulosin along with deflazacort post ESWL for renal and upper ureteric calculi increases the stone expulsion rate and reduces the expulsion duration as shown by highly statistically significant results in group C. [Int J Res Med Sci 2016; 4(2.000: 643-648

  9. Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure.

    Science.gov (United States)

    Pérez-Fontán, Miguel; Cordido, Fernando; Rodríguez-Carmona, Ana; Penín, Manuel; Díaz-Cambre, Helena; López-Muñiz, Andrés; Sangiao-Alvarellos, Susana; García-Buela, Jesús

    2008-11-01

    Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P anorexia of chronic renal failure.

  10. Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

    Science.gov (United States)

    Verma, Akhilesh Kumar; Chandra, Subhash; Singh, Rana Gopal; Singh, Tej Bali; Srivastava, Shalabh; Srivastava, Ragini

    2014-01-01

    Association of oxidative stress and serum prolidase activity (SPA) has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN) and end stage renal disease (ESRD) concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased (P < 0.001). Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2 (P < 0.001). Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1 (P < 0.001). In case-2, serum creatinine was significantly correlated with SPA only (P < 0.001). Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage. PMID:25276429

  11. Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

    Directory of Open Access Journals (Sweden)

    Akhilesh Kumar Verma

    2014-01-01

    Full Text Available Association of oxidative stress and serum prolidase activity (SPA has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN and end stage renal disease (ESRD concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS, total antioxidant status (TAS, and oxidative stress index (OSI were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased (P<0.001. Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2 (P<0.001. Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1 (P<0.001. In case-2, serum creatinine was significantly correlated with SPA only (P<0.001. Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage.

  12. Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models

    OpenAIRE

    Yin Liang; Kenji Arakawa; Kiichiro Ueta; Yasuaki Matsushita; Chiaki Kuriyama; Tonya Martin; Fuyong Du; Yi Liu; June Xu; Bruce Conway; Jamie Conway; David Polidori; Kirk Ways; Keith Demarest

    2012-01-01

    BACKGROUND: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). METHODS: (14)C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3)H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose e...

  13. Linagliptin Limits High Glucose Induced Conversion of Latent to Active TGFß through Interaction with CIM6PR and Limits Renal Tubulointerstitial Fibronectin.

    Directory of Open Access Journals (Sweden)

    Muralikrishna Gangadharan Komala

    Full Text Available In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4 inhibitors have been shown to be antifibrotic. We have previously shown that cation independent mannose-6-phosphate receptor (CIM6PR facilitates the conversion of latent to active transforming growth factor β1 (GFß1 in renal proximal tubular cells (PTCs and linagliptin (a DPP4 inhibitor reduced this conversion with downstream reduction in fibronectin transcription.We wanted to demonstrate that linagliptin reduces high glucose induced interaction between membrane bound DPP4 and CIM6PR in vitro and demonstrate reduction in active TGFß mediated downstream effects in a rodent model of type 1 diabetic nephropathy independent of high glycaemic levels.We used human kidney 2 (HK2 cells and endothelial nitric oxide synthase knock out mice to explore the mechanism and antifibrotic potential of linagliptin independent of glucose lowering. Using a proximity ligation assay, we show that CIM6PR and DPP4 interaction was increased by high glucose and reduced by linagliptin and excess mannose-6-phosphate (M6P confirming that linagliptin is operating through an M6P-dependent mechanism. In vivo studies confirmed these TGFß1 pathway related changes and showed reduced fibronectin, phosphorylated smad2 and phosphorylated smad2/3 (pSmad2/3 with an associated trend towards reduction in tubular atrophy, which was independent of glucose lowering. No reduction in albuminuria, glomerulosclerotic index or cortical collagen deposition was observed.Linagliptin inhibits activation of TGFß1 through a M6P dependent mechanism. However this in isolation is not sufficient to reverse the multifactorial nature of diabetic nephropathy.

  14. Mitochondrial Fission Increases Apoptosis and Decreases Autophagy in Renal Proximal Tubular Epithelial Cells Treated with High Glucose.

    Science.gov (United States)

    Lee, Wen-Chin; Chiu, Chien-Hua; Chen, Jin-Bor; Chen, Chiu-Hua; Chang, Hsueh-Wei

    2016-11-01

    The aim of this study was to examine the effect of mitochondrial morphogenesis changes on apoptosis and autophagy of high-glucose-treated proximal tubular epithelial cells (HK2). Cell viability, apoptosis, and mitochondrial morphogenesis were examined using crystal violet, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and mitotracker staining, respectively. High glucose inhibited cell viability and induced mitochondrial fission in HK2 cells. After depleting mitofusin 1 (MFN1), the MFN1(-) HK2 cells (fission type) became more susceptible to high-glucose-induced apoptosis and mitochondrial fragmentation observed by TUNEL and mitotracker assays. In siMFN2 HK2 cells (fission type), mitochondria were highly fragmented (>80% fission rate) with or without high-glucose treatment; however, siFIS1 (mitochondrial fission protein 1) HK2 cells (fusion type) exhibited little fragmentation (High-glucose treatment induced autophagy, characterized by the formation of autophagosome and microtubule-associated protein light chain 3 (LC3) B-II, as observed by transmission electron microscopy and western blotting, respectively. LC3B-II levels decreased in both MFN1(-) and siMFN2 HK2 cells, but increased in siFIS1 HK2 cells. Moreover, autophagy displays a protective role against high-glucose-induced cell death based on cotreatment with autophagy inhibitors (3-methyladenine and chloroquine). Mitochondrial fission may increase apoptosis and decrease autophagy of high-glucose-treated HK2 cells.

  15. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

    OpenAIRE

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R.; Thomson, Scott C.; Koepsell, Hermann; Vallon, Volker

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the ...

  16. Resistance of the rat to development of lead-induced renal functional deficits

    Energy Technology Data Exchange (ETDEWEB)

    O' Flaherty, E.J.; Adams, W.D.; Hammond, P.B.; Taylor, E.

    1986-01-01

    Lead nephropathy, characterized functionally by depression of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and maximum glucose reabsorption rate, is associated with prolonged occupational exposure to lead. Production of comparable lead-related renal functional deficits in rats has been difficult to achieve. The authors have examined in rats some of the factors that might be expected to influence the development of lead-induced renal functional damage, using GFR (as inulin clearance). ERPF (as para-aminohippurate clearance), and maximum glucose readsorption rates as indices of renal functional competence. Although lead produces a significant weight loss, this can be accounted for by reduced food intake and is not associated with reduction in renal function. Even exposure to large amounts of lead in conjunction with other factors; such as controlled diet (NIH-07 and AIN-76) and early age of initial exposure, that might have been expected to increase the rats' susceptibility has not resulted in the development of renal functional deficits. It is unlikely that the rat can be successfully explored as an animal model of human lead nephropathy with accompanying functional deficits.

  17. Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS).

    Science.gov (United States)

    Varma, Manthena V; Steyn, Stefanus J; Allerton, Charlotte; El-Kattan, Ayman F

    2015-12-01

    Early prediction of clearance mechanisms allows for the rapid progression of drug discovery and development programs, and facilitates risk assessment of the pharmacokinetic variability associated with drug interactions and pharmacogenomics. Here we propose a scientific framework--Extended Clearance Classification System (ECCS)--which can be used to predict the predominant clearance mechanism (rate-determining process) based on physicochemical properties and passive membrane permeability. Compounds are classified as: Class 1A--metabolism as primary systemic clearance mechanism (high permeability acids/zwitterions with molecular weight (MW) ≤400 Da), Class 1B--transporter-mediated hepatic uptake as primary systemic clearance mechanism (high permeability acids/zwitterions with MW >400 Da), Class 2--metabolism as primary clearance mechanism (high permeability bases/neutrals), Class 3A--renal clearance (low permeability acids/zwitterions with MW ≤400 Da), Class 3B--transporter mediated hepatic uptake or renal clearance (low permeability acids/zwitterions with MW >400 Da), and Class 4--renal clearance (low permeability bases/neutrals). The performance of the ECCS framework was validated using 307 compounds with single clearance mechanism contributing to ≥70% of systemic clearance. The apparent permeability across clonal cell line of Madin - Darby canine kidney cells, selected for low endogenous efflux transporter expression, with a cut-off of 5 × 10(-6) cm/s was used for permeability classification, and the ionization (at pH7) was assigned based on calculated pKa. The proposed scheme correctly predicted the rate-determining clearance mechanism to be either metabolism, hepatic uptake or renal for ~92% of total compounds. We discuss the general characteristics of each ECCS class, as well as compare and contrast the framework with the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS

  18. Multifunctional Mesoporous Silica Nanospheres with Cleavable Gd(III) Chelates as MRI Contrast Agents: Synthesis, Characterization, Target-Specificity, and Renal Clearance

    Science.gov (United States)

    Vivero-Escoto, Juan L.; Taylor-Pashow, Kathryn M. L.; Huxford, Rachel C.; Rocca, Joseph Della; Okoruwa, Christie; An, Hongyu; Lin, Weili

    2013-01-01

    Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox-responsive disulfide moiety. The MSNs are further functionalized with polyethylene glycol (PEG) and an anisamide ligand to improve their biocompatibility and target specificity. The effectiveness of MSNs as an MRI imaging contrast agent and their targeting ability are successfully demonstrated in vitro using human colon adenocarcinoma and pancreatic cancer cells. Finally, the capability of this platform as an in vivo MRI contrast agent is tested using a 3T scanner. The Gd(III) chelate was quickly cleaved by the blood pool thiols and eliminated through the renal excretion pathway. Further tuning of the Gd(III) chelate release kinetics is needed before the MSN system can be used as target-specific MRI contrast agents in vivo. PMID:22069305

  19. Evaluation of White Sesame Seed Oil on Glucose Control and Biomarkers of Hepatic, Cardiac, and Renal Functions in Male Sprague-Dawley Rats with Chemically Induced Diabetes.

    Science.gov (United States)

    Aslam, Farhan; Iqbal, Sanaullah; Nasir, Muhammad; Anjum, Aftab Ahmad; Swan, Pamela; Sweazea, Karen

    2017-05-01

    White sesame seed oil (WSSO) has been used in cooking and food preparations for centuries. It has many purported health benefits and may be a promising nutraceutical. The primary purpose of this study was to examine the effects of WSSO on fasting blood glucose (GLU) and insulin (INS) in male Sprague-Dawley rats with chemically induced diabetes. A secondary aim was to explore other hematological biomarkers of hepatic, cardiac, and renal function. Sixty-three male Sprague-Dawley rats were randomized into standard diet groups, normal control (NCON) (n = 21) and diabetic control (DCON) (n = 21), and a diabetic sesame oil (DSO) (n = 21) group, which were fed a diet containing 12% WSSO. Blood samples were analyzed at 0, 30, and 60 days. Differences between groups and across days were assessed with two-way repeated measures analysis of variance. At baseline, GLU and INS were similar in both diabetic groups, mean 248.4 ± 2.8 mg/dL and mean 23.4 ± 0.4 μU/mL, respectively. At 60 days, GLU was significantly (P < .05) higher in DCON (298.0 ± 2.3 mg/dL) compared with DSO (202.1 ± 1.0 mg/dL). INS showed similar favorable trends after WSSO supplementation. Consumption of WSSO significantly improved glucose control and other biomarkers of hepatic stress, as well as cardiac and renal health. WSSO may be a viable functional food to help reduce the detrimental effects of diabetes.

  20. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma.

    Science.gov (United States)

    Lucarelli, Giuseppe; Galleggiante, Vanessa; Rutigliano, Monica; Sanguedolce, Francesca; Cagiano, Simona; Bufo, Pantaleo; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico; Giglio, Andrea; Serino, Grazia; Vavallo, Antonio; Bettocchi, Carlo; Selvaggi, Francesco Paolo; Battaglia, Michele; Ditonno, Pasquale

    2015-05-30

    The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the regulation of ccRCC redox homeostasis. Patients with high levels of glycolytic enzymes had reduced progression-free and cancer-specific survivals as compared to subjects with low levels. Our data suggest that oncogenic signaling pathways may promote ccRCC through rerouting the sugar metabolism. Blocking the flux through this pathway may serve as a novel therapeutic target.

  1. Validation of a Novel Method for Determining the Renal Threshold for Glucose Excretion in Untreated and Canagliflozin-treated Subjects With Type 2 Diabetes Mellitus

    Science.gov (United States)

    Sha, Sue; Ghosh, Atalanta; Plum-Mörschel, Leona; Heise, Tim; Rothenberg, Paul

    2013-01-01

    Context: The stepwise hyperglycemic clamp procedure (SHCP) is the gold standard for measuring the renal threshold for glucose excretion (RTG), but its use is limited to small studies in specialized laboratories. Objective: The objective of the study was to validate a new method for determining RTG using data obtained during a mixed-meal tolerance test (MMTT) in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus (T2DM). Design: This was an open-label study with 2 sequential parts. Setting: The study was performed at a single center in Germany. Patients: Twenty-eight subjects with T2DM were studied. Interventions: No treatment intervention was given in part 1. In part 2, subjects were treated with canagliflozin 100 mg/d for 8 days. In each part, subjects underwent an MMTT and a 5-step SHCP on consecutive days. Main Outcome Measures: For both methods, RTG was estimated using measured blood glucose (BG) and urinary glucose excretion (UGE); estimated glomerular filtration rates were also used to determine RTG during the MMTT. The methods were compared using the concordance correlation coefficient and geometric mean ratios. Results: In untreated and canagliflozin-treated subjects, the relationship between UGE rate and BG was well described by a threshold relationship. Good agreement was obtained between the MMTT-based and SHCP-derived RTG values. The concordance correlation coefficient (for all subjects) was 0.94; geometric mean ratios (90% confidence intervals) for RTG values (MMTT/SHCP) were 0.93 (0.89–0.96) in untreated subjects and 1.03 (0.78–1.37) in canagliflozin-treated subjects. Study procedures and treatments were generally well tolerated in untreated and canagliflozin-treated subjects. Conclusions: In both untreated and canagliflozin-treated subjects with T2DM, RTG can be accurately estimated from measured BG, UGE, and estimated glomerular filtration rates using an MMTT-based method. PMID:23585665

  2. Evaluation of {sup 123}I-orthoiodohippurate single kidney clearance rate by renal sequential scintigraphy in a large cohort of likely normal subjects aged between 0 and 18 years

    Energy Technology Data Exchange (ETDEWEB)

    Imperiale, Alessio; Olianti, Catia; Comis, Giannetto; Cava, Giuseppe la [University of Florence, Nuclear Medicine Unit, Department of Clinical Pathophysiology, Florence (Italy)

    2006-12-15

    Age-related values of{sup 123}I-orthoiodohippurate (OIH) single kidney clearance rate (Cl) were estimated in a large cohort of likely normal children aged between 0 and 18 years. Among 4,111 children examined in the past 10 years, 917 were selected with the following inclusion criteria: (a) mild ultrasonographic hydronephrosis with right differential renal function (DRF) <53% and >47% (498 pts), (b) known or suspected urinary tract infection with normal ultrasound, serum creatinine and DMSA and DRF <53% and >47% (419 pts).{sup 123}I-OIH-Cl was assessed using a validated gamma camera method. Children were divided into 21 age classes: from 0 to 2 years, eight 3-month classes; from 2 to 14 years, twelve 1-year classes; from 14 to 18 years, one 4-year class. Cl, plotted against age, was fitted using an increasing function (y = a - be - cx). Mean{sup 123}I-OIH-Cl of 1,834 kidneys was 306{+-}22 ml/min/1.73 m{sup 2} BSA. Mean{sup 123}I-OIH-Cl of the right and left kidneys was 307{+-}23 and 305{+-}22 ml/min/1.73 m{sup 2} BSA, respectively (p<0.002). The best-fitting{sup 123}I-OIH-Cl growing function was: Cl=311-230e-0.69 x Age (months).{sup 123}I-OIH-Cl improved progressively starting from birth, reaching 96% and 98% of the mature value at 1 and 1.5 years, respectively.{sup 123}I-OIH-Cl at birth (age=0) was 81 ml/min/1.73 m{sup 2} BSA. After 18.6 days of life, the renal function had doubled its starting value, and it reached a plateau of 311 ml/min/1.73 m{sup 2} BSA at 2 years. This work represents a systematic evaluation of ERPF by a gamma camera method in a large cohort of selected likely normal paediatric subjects. (orig.)

  3. Creatinine clearance test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003611.htm Creatinine clearance test To use the sharing features on this page, please enable JavaScript. The creatinine clearance test helps provide information about how well the ...

  4. Creatinine clearance as predictor of tobramycin elimination in adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Touw, D.J.; Vinks, A.A.T.M.M.; Jacobs, F.; Heijerman, H.G.M.; Bakker, Wim

    1996-01-01

    Assessment of renal function and relating this parameter to aminoglycoside clearance is important for an appropriate individualization of dosage regimens in patients with impaired renal function. However, it has been suggested that in cystic fibrosis (CF), creatinine clearance (CrCl) is not a good p

  5. Enhancement of the amylase-creatinine clearance ratio in pregnancy.

    Science.gov (United States)

    Naeije, R; Neuray, F; Van Melsen, A; Delcourt, A

    1979-01-01

    The renal clearance of amylase, expressed as a proportion of simultaneous creatinine clearance (Cam/-Ccr), was determined in 131 women in various stages of pregnancy. No abnormal serum levels of amylase were found. A moderate but significant increase in Cam/Ccr occurred during the last 15 weeks of pregnancy. Possible causes for this change were investigated in smaller groups of subjects. No increase in rapidly cleared isoamylase could be detected. No modification in renal tubular handling of protein could be evidenced, as assessed by measurements of the renal clearance of beta 2 microglobulin, expressed as a proportion of simultaneous creatinine clearance. An incrased glomerular permeability to amylase probably accounts for elevated Cam/Ccr in pregnancy.

  6. c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Huang, Jiwei; Kong, Wen; Zhang, Jin; Chen, Yonghui; Xue, Wei; Liu, Dongming; Huang, Yiran

    2016-10-01

    Renal cell carcinoma (RCC) is one of the most malignant tumors worldwide. Among all subtypes of RCC, clear-cell RCC (ccRCC) is the most common and aggressive one. The difficulty in overcoming resistance of traditional treatment is a threat for ccRCC therapies. Therefore, to understand the mechanism that underlies ccRCC progression is critical for new drug development. In the present study, we identified that miR-184 could be downregulated by c-Myc, which is different from the standard opinion that c-Myc is a target of miR-184. Overexpression of pre-miR-184 changed the metabolic and proliferation features of ccRCC cells by reducing cell glucose consumption, lactate production and cell proliferation. Further analysis by computer bioinformatics revealed that PKM2 is a target of miR-184. Both PKM2 mRNA and protein were significantly affected by addition of miR-184. Importantly, the PKM2 expression level was indeed increased in ccRCC samples, which is totally reverse compared to the decreased miR-184 expression level. Interestingly, we found that when PKM2 was knocked down in ccRCC cells, the rapid proliferation, high glucose consumption and high lactate production were all clearly inhibited, which indicates metabolic reprogramming and cancer progression blocking the in ccRCC cells. Our findings shed new light on ccRCC molecular study and provide a new and solid basis for developing ccRCC therapy.

  7. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Parichehr Hayatdavoudi

    2015-11-01

    Full Text Available Objective(s: Leptin exerts various effects on appetite and body weight. Disruption of the obesitygene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P

  8. Security Clearance Tracking System

    Data.gov (United States)

    National Archives and Records Administration — SCTS supports the adjudication process of private background investigations and clearances for potential employees, contractors, interns and student workers.

  9. Effect of nitrendipine on renal function and on hormonal parameters after intravascular iopromide

    DEFF Research Database (Denmark)

    Madsen, J K; Jensen, J W; Sandermann, J

    1998-01-01

    . Renal tubular function was estimated from the clearance of lithium. Hormones were measured by radioimmunoassays. RESULTS: Arteriography with iopromide did not change renal function. No differences between the nitrendipine and placebo groups were found in renal hemodynamics, tubular sodium handling...

  10. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    Science.gov (United States)

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim

    2017-09-12

    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Lu, Yasong; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  12. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Yasong eLu; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  13. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Yasong eLu; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  14. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Lu, Yasong; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  15. The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

    Science.gov (United States)

    Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

    2011-05-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were...... measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...... to fall in the sitting position, and fell significantly to 26 +/- 5 ml/min (p less than 0.025) in walking subjects. Absolute proximal tubular reabsorption rate of fluid correspondingly rose from 83 +/- 16 to 92 +/- 15 ml/min (p less than 0.005) and sodium clearance fell from 1.52 +/- 0.81 to 1.00 +/- 0...

  17. Fasting blood glucose and prognosis of patients surviving over 1 year after renal transplantation%肾移植后1年存活者空腹血糖变化及预后

    Institute of Scientific and Technical Information of China (English)

    王莉

    2015-01-01

    背景:肾移植后糖尿病是移植脏器的重要代谢并发症,严重影响患者生活质量与长期生存率,是移植肾失功能、心血管疾病的危险因素。目的:观察肾移植后存活1年以上患者空腹血糖变化规律以及对预后的影响。方法:选取2003年1月至2013年1月接受过肾移植后来仙桃市第一人民医院就诊的患者42例,其中移植前糖尿病患者7例、空腹血糖受损组11例和空腹血糖正常患者24例,观察各组患者移植后1,7,14 d以及1,3,6,12个月空腹血糖变化,并比较各组移植后生存情况,采用Cox比例风险模型分析影响肾移植患者生存的因素。结果与结论:糖尿病组患者移植前及移植后各时间段空腹血糖明显高于空腹血糖受损和空腹血糖正常组患者(P <0.05),糖尿病、空腹血糖受损和空腹血糖正常组患者空腹血糖在移植后第1天均升高(P <0.05),各组空腹血糖在移植后3个月趋于平稳;空腹血糖正常组生存率明显高于糖尿病组和空腹血糖受损组(P<0.05)。Cox 比例风险模型分析结果显示,移植前空腹血糖、年龄、移植后肿瘤和感染是肾移植患者死亡的独立危险因素,其中移植后发生肿瘤的死亡危险比最高,为2.376。结果证实,移植前糖尿病对肾移植后存活1年以上患者生存率有一定的影响,移植后糖尿病对患者生存率的无明显影响。%BACKGROUND:Diabetes mel itus after kidney transplantation is an important metabolic complication of the transplanted organ, and seriously affects the quality of life and long-term survival rate of patients, which is a risk factor for renal al ograft dysfunction and cardiovascular disease. OBJECTIVE:To investigate the changes in fasting blood glucose and prognosis of patients who had survived more than 1 year after renal transplantation. METHODS:Total y 42 patients undergoing renal transplantation admitted at Xiantao First

  18. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats.

    Science.gov (United States)

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L

    1999-08-31

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  19. Comparison of icodextrin and glucose solutions for long dwell exchange in peritoneal dialysis: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Qi, Hualin; Xu, Chen; Yan, Haidong; Ma, Jun

    2011-01-01

    Icodextrin is widely used in peritoneal dialysis (PD); however, the safety and efficacy of icodextrin are unclear. In the present study, we performed a systematic review of randomized controlled trials (RCTs) that compared icodextrin and glucose for the once-daily long dwell in PD. Electronic searches were performed in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to select all eligible studies. Eligible studies, as determined by consensus using predefined criteria, were reviewed, and data were extracted onto a standard form. In the 9 RCTs that were identified, patients using icodextrin were found to have much greater net ultrafiltration (UF) and a lower incidence of negative net UF compared to patients using 1.5%, 2.5%, and 4.25% glucose solutions. Additionally, icodextrin has a markedly increased UF efficiency ratio and peritoneal clearance of creatinine and urea nitrogen, but residual renal function was not different from patients using glucose solutions for PD. No significant differences were observed between icodextrin and glucose groups with respect to risk of mortality, peritonitis, and total adverse events. Although rashes occurred significantly more often in icodextrin groups, few differences were noted between icodextrin and glucose groups when withdrawal rates secondary to adverse events were compared. This meta-analysis suggests that icodextrin provides patients with greater fluid removal and small solute clearance and does not cause any damage to residual renal function. Icodextrin is particularly appropriate for use in patients with high peritoneal transport status.

  20. [Radioisotopic quantification of kidney function using Tc-99m-DMSA. Comparison with creatinine clearance in children with a single kidney].

    Science.gov (United States)

    Baillet, G; Gagnadoux, M F; Mathonnat, F; de Vernejoul, P; Broyer, M

    1986-01-01

    To assess the accuracy of renal function quantification with Tc 99m-DMSA in children, we compared DMSA renal uptake and creatinine clearance in 16 cases of children with single kidney. The age of the patients ranged from two month to fourteen years. DMSA renal uptake was measured 7 hours after injection and was normalized in percent of the injected activity. A significant correlation was found between creatinine clearance and DMSA uptake (Pearson's r = 0.866, p less than 0.01). Normal creatinine clearance in children (80 to 120 ml/min-1 X 1.73 m-2) allowed determination of normal renal uptake (36 to 60%). This study indicates that in cases of asymmetrical renal impairment renal uptake reflects split renal creatinine clearance. Since the former is much easier to measure, DMSA should play an important role in the evaluation of differential renal function.

  1. Influence of renal function on the elimination of morphine and morphine glucuronides

    DEFF Research Database (Denmark)

    Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

    1988-01-01

    plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...

  2. Chronic Renal Failure, Cachexia, and Ghrelin

    OpenAIRE

    Laviano, A.; Krznaric, Z.; Sanchez-Lara, K.; Preziosa, I.; Cascino, A; Rossi Fanelli, F.

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Neverth...

  3. Endothelin receptor A antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs.

    Directory of Open Access Journals (Sweden)

    Johan Fenhammar

    Full Text Available BACKGROUND: Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors. METHODS AND FINDINGS: A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg(-1, n = 8 or served as endotoxin-treated controls (n = 8. Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002. Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p<0.05 measured by microdialysis. Furthermore, TBC 3711 attenuated the decline in renal cortical interstitial glucose levels (p = 0.02 and increased medullary pyruvate levels (p = 0.03. Decreased creatinine clearance and oliguria were present in both groups without any significant difference. CONCLUSIONS: These results suggest that endothelin released during endotoxemia acts via endothelin A receptors to impair renal medullary blood flow causing ischemia. Reduced renal oxygen extraction and cortical levels of lactate by TBC 3711, without effects on cortical blood flow, further suggest additional metabolic effects of endothelin type A receptor activation in this model of endotoxin induced acute kidney injury.

  4. Pharmacokinetic and pharmacodynamic profiles of canagliflozin in Japanese patients with type 2 diabetes mellitus and moderate renal impairment.

    Science.gov (United States)

    Inagaki, Nobuya; Kondo, Kazuoki; Yoshinari, Toru; Ishii, Manabu; Sakai, Masaki; Kuki, Hideki; Furihata, Kenichi

    2014-10-01

    This study examined the effects of moderate renal impairment on the pharmacokinetics and pharmacodynamics of canagliflozin in Japanese patients with type 2 diabetes mellitus. Japanese patients with stable type 2 diabetes (12 with moderate renal impairment and 12 with normal renal function or mild renal impairment) were eligible. This was an open-label, randomized, two-way crossover, two-sequence, single-dose study performed at a single center in Japan. The subjects were hospitalized for the pharmacodynamic/pharmacokinetic evaluations. Twenty-four patients received a single dose each of canagliflozin 100 and 200 mg before breakfast in a crossover manner with a 14-day washout between doses. The main outcome measures were pharmacokinetics of canagliflozin and its main metabolites (M5 and M7) in plasma and urine, and change from baseline in 24-h urinary glucose excretion (ΔUGE24 h). There was no significant effect of moderate renal impairment on the maximum canagliflozin concentration. The ratios of least square means (90 % confidence intervals [CIs]) of moderate renal impairment relative to normal renal function or mild renal impairment were 0.982 (0.821-1.173) and 0.989 (0.827-1.182) for the 100 and 200 mg doses, respectively. The canagliflozin area under the plasma concentration-time curve was greater in those with moderate renal impairment than in those without, after both canagliflozin doses (ratio of least square means [90 % CI] 1.258 [1.061-1.490] and 1.216 [1.026-1.441]). ΔUGE24 h increased after administration of both doses, but in patients with moderate renal impairment, the increase was approximately 70 % of that in patients with normal renal function or mild renal impairment. The incidence of adverse events was low and no patient developed hypoglycemia. The pharmacokinetics of canagliflozin are affected by renal function, with slight decreases in renal clearance observed. No effect of renal impairment on the maximum concentration was observed. Renal

  5. Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals

    Directory of Open Access Journals (Sweden)

    Edoardo Vitolo

    2016-10-01

    Full Text Available Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR is unusual, and how estimation formulae (EstForm perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR by iohexol plasma clearance, renal plasma flow (RPF by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis. mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67, accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.

  6. THE EFFECTS OF REGULAR AEROBIC EXERCISE ON RENAL FUNCTIONS IN STREPTOZOTOCIN INDUCED DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    Hatice Kurdak

    2010-06-01

    Full Text Available Diabetic nephropathy is a feared complication of diabetes since it can lead to end-stage renal failure and also it is a risk factor of cardiovascular disease. The important clinical problems caused by diabetic nephropathy are proteinuria and decreased renal function. Exercise is a cornerstone of diabetes management, along with diet and medication. Since acute exercise causes proteinuria and decreases glomerular filtration rate, the effect of exercise on diabetic nephropathy is controversial. The aim of this study was to investigate the effect of regular aerobic exercise on microalbuminuria and glomerular filtration rate in diabetic rats. Moderate diabetes was induced by streptozotocin (45 mg/kg IV in rats and an aerobic exercise- training program on a treadmill was carried out for 8 weeks. Four groups of rats; control sedentary (CS, control exercise (CE, diabetic sedentary (DS and diabetic exercise (DE were included in the study. Blood glucose levels were determined from the plasma samples taken at the end of 4 weeks of stabilization period and 8 weeks of training program. Creatinine clearance (CCr and microalbuminuria (MA levels were determined to evaluate renal functions. The analyzed data revealed that regular aerobic exercise: 1 significantly decreased the plasma glucose level of the DE group compared to the DS group (p < 0.05, 2 significantly decreased the microalbuminuria level of the DE group compared to those of DS group (p < 0.01, 3 significantly decreased the creatinine clearance levels of the DE and CE groups compared to those of CS group (p < 0.05. The results of this study suggest that despite of decreasing creatinine clearance, regular submaximal aerobic exercise has a preventive effect on development of microalbuminuria and thus may retard nephropathy in diabetic rats

  7. The kidneys play a central role in the clearance of rhGH in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads;

    2016-01-01

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted...... at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...

  8. Increased hepatic insulin clearance after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils B;

    2013-01-01

    Context:Roux-en-Y gastric bypass (RYGB) improves glucose tolerance and ameliorates fasting hyperinsulinemia within days after surgery. Improvements in hepatic insulin sensitivity and insulin clearance could contribute importantly to these effects.Objective:The objective of the investigation...... was to study changes in insulin clearance after RYGB.Design:This was a prospective study of fasting hepatic insulin clearance and, in a subgroup of patients, postprandial insulin clearance after a meal test before and 1 week, 3 months, and 1 year after RYGB.Setting:The study was conducted at Hvidovre Hospital......:Fasting hepatic insulin clearance (fasting C-peptide/fasting insulin). Postprandial insulin clearance (incremental areas under the curve of insulin secretion rates/incremental areas under the curve of insulin).Results:Fasting hepatic insulin clearance increased after 1 week (P

  9. Effect of sludge ice cooling on renal function and renal histology in the dog.

    Science.gov (United States)

    Verbaeys, A; Oosterlinck, W; Lameire, N; Cuvelier, C; De Sy, W A

    1981-01-01

    The effect of sludge ice surface cooling on the compensatory hypertrophied dog kidney was investigated. Renal function was measured prior to and on days 1, 3 and 7 after the cooling procedure by means of inulin clearance, PAH clearance and sodium excretion capacity during normal hydration and after volume expansion. No alteration in renal function was shown. No freezing lesions or thromboses were seen on histological examination.

  10. Effect of metabolic regulation on renal leakiness to dextran molecules in short-term insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Rutili, F; Granath, K;

    1979-01-01

    Renal clearance of dextran of two ranges of molecular size and glomerular filtration rate (GFR, 51Cr-EDTA) were measured in seven short-term insulin-dependent diabetics (mean age 25 years). Measurements were carried out in the same patient during good and poor metabolic regulation (plasma glucose...... were normalized within one to three weeks of effective insulin treatment. This rapid reversibility can hardly be explained by the previously demonstrated enlargement in glomerular size and filtration surface area, since these alterations remain unchanged after more than one month of insulin treatment...

  11. Inter-relationships between renal metabolism (both in physiology and renal dysfunction) and the liver.

    Science.gov (United States)

    Cano, N

    2001-07-01

    Recently, evaluation of organ-specific glucose release showed that renal glucose release is of the same order of magnitude as splanchnic glucose release during the postabsorptive period. Moreover, renal glucose release appeared to be more sensitive to hormone action than did hepatic glucose release, and appeared to have a pre-eminent role during the adaptation to various physiological and pathological conditions. The kidney is now recognized as playing a key role in interorgan glucose metabolism, and particularly in the Cori cycle and glutamine-glucose cycle. During chronic renal failure the suppression of renal glucose release, together with impaired hormone action, decreased glycogen storage and abnormal liver gluconeogenesis, are responsible for an increased risk for hypoglycaemia.

  12. The effect of nifedipine on renal function in normotensive cyclosporin-A-treated renal allograft recipients.

    Science.gov (United States)

    McNally, P G; Walls, J; Feehally, J

    1990-01-01

    Intrarenal vasoconstriction is a characteristic feature of CsA nephrotoxicity. The influence of nifedipine, a dihydropyridine calcium channel blocker and potent renal vasodilator, on renal haemodynamics was investigated in 11 cyclosporin A (CsA)- and 9 azathioprine (Aza)-treated normotensive long-term renal allograft recipients. Baseline Cr51-EDTA clearance and effective renal plasma flow (ERPF) were similar in both groups. Nifedipine 20 mg twice daily for 28 days significantly increased Cr51-EDTA clearance (+14.8%) in the CsA group; however, ERPF, renal vascular resistance (RVR), and filtration fraction did not change. Nifedipine did not influence renal haemodynamics in the azathioprine group. The increase in Cr51-EDTA clearance in the CsA group did not correlate with baseline renal function, CsA dose or whole blood levels, donor age, duration of graft, or renal functional reserve capacity. This study suggests that nifedipine confers a beneficial effect on renal haemodynamics in long-term CsA-treated renal allograft recipients and appears to improve renal function by a non-haemodynamic mechanism.

  13. Elimination and Degradation of Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in Patients with End-Stage Renal Disease

    DEFF Research Database (Denmark)

    Idorn, Thomas; Knop, Filip K; Jørgensen, Morten B;

    2014-01-01

    Context: The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear. Objective: To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with d...

  14. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Qingqiao [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Wang, Guan [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University (China)

    2016-09-02

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.

  15. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

    Science.gov (United States)

    Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

    2016-09-02

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.

  16. Site clearance working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  17. Distribution and kinetics of glucose in rats analyzed by noncompartmental and compartmental analysis

    Energy Technology Data Exchange (ETDEWEB)

    Raman, M.; Radziuk, J.; Hetenyi, G. Jr. (Univ. of Ottawa, Ontario (Canada))

    1990-08-01

    The steady-state kinetics and distribution of glucose were assessed using noncompartmental and various two-compartment models in rats that were infused with insulin (+/- euglycemic clamping), methylprednisolone (MP), or phlorizin (PHL) as well as rats injected with protamine-zinc-insulin (PZI) or rendered diabetic. Decreases in clearance of glucose (PCR) were greatest with insulin infusion, followed by PHL, MP, and PZI treatments. PCR decreased in diabetes to 25% of normal. With hyperinsulinemia and euglycemia, turnover rates were 1.18 times the rate of glucose infusion. In normal rats the ratio of the contents of the two compartments was 0.6-0.8 (depending on the model). Significant increases, of between 2.8 and 5.2, were observed with insulin infusion and between 0.8 and 1.8 with PHL, again depending on the model. Because PHL-induced changes in PCR are renal, these data suggest that variations in glucose distribution depend on changes in PCR as well as insulin. The intercompartmental rate constant decreased, and the noncompartmental volume of distribution increased to reflect the above changes. In non-steady-state studies, glucose release increased in response to insulin but not to PHL in contrast to other species.

  18. The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention

    DEFF Research Database (Denmark)

    Henriksen, Ulrik L; Henriksen, Jens H

    2014-01-01

    In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy...

  19. Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

    1988-01-01

    Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

  20. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

    Science.gov (United States)

    Hansen, J M; Løkkegaard, H; Høy, C E; Fogh-Andersen, N; Olsen, N V; Strandgaard, S

    1995-01-01

    Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

  1. Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

    Directory of Open Access Journals (Sweden)

    Nasu,Yasutomo

    2006-04-01

    Full Text Available We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3 renal scintigraphy before and after radiofrequency ablation (RFA of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women ; age range : 23-83 years ; mean age : 60.6 years. Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

  2. Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Shahnaz Atabak

    2013-01-01

    Full Text Available Peritoneal dialysis offers several advantages such as better clearance of intermediate/large molecules and better preservation of renal residual function when compared with hemodialysis. However, dialysis adequacy is one of the subjects of concern of this modality. There are some drugs that are capable of influencing solute transport in the peritoneum, such as acetyle co-enzyme inhibitors (ACE-I medications and calcium channel blockers. Captopril and Verapamil are often mentioned, but their use has shown varying conclusions and initial studies were performed with the intra-peritoneal administration of these drugs and there are only a few studies on the effect of the oral administration of these drugs. This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET test. However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti-hypertensive medication of choice in CAPD patients, which can also result in better dialysis adequacy. However, further studies with larger sample sizes are needed in the future.

  3. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Directory of Open Access Journals (Sweden)

    Sarika Kapoor

    Full Text Available The sodium-glucose-cotransporter-2 (SGLT2 inhibitor dapagliflozin (DAPA induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD, we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group. Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d. DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  4. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Science.gov (United States)

    Kapoor, Sarika; Rodriguez, Daniel; Riwanto, Meliana; Edenhofer, Ilka; Segerer, Stephan; Mitchell, Katharyn; Wüthrich, Rudolf P

    2015-01-01

    The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  5. Turbomachinery Clearance Control

    Science.gov (United States)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  6. 32 CFR 154.48 - Issuing clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Issuing clearance. 154.48 Section 154.48... PERSONNEL SECURITY PROGRAM REGULATION Issuing Clearance and Granting Access § 154.48 Issuing clearance. (a... personnel security clearance in the DCII (see § 154.43). A record of the clearance issued shall also...

  7. 24 CFR 35.1340 - Clearance.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Clearance. 35.1340 Section 35.1340... Hazard Evaluation and Hazard Reduction Activities § 35.1340 Clearance. Clearance examinations required... provisions of this section. (a) Clearance following abatement. Clearance examinations performed...

  8. Reforming Customs Clearance in Pakistan

    OpenAIRE

    Ahmad, Manzoor

    2010-01-01

    Simple, fast, transparent customs clearance procedures encourage trade-and the resulting tariffs and related taxes raise government revenue and stimulate economic development. After outsourcing failed to make customs more efficient or increase revenue, in 2002 Pakistan began pursuing a modern single window system for customs clearance. In 2005 the system was introduced at the port of Karac...

  9. Aerial Refueling Clearance Initiation Request

    Science.gov (United States)

    2016-07-14

    fund sharing options.................................................................................. 18 3.12 ATP 3.3.4.2...publication of the original document and its eventual publication in ATP -56 (B). Workgroup 5 spent several Workgroup/JSB sessions reviewing and updating...Clearance Compatibility Assessment Checklist. 21 Aug 2014 ATP 3.3.4.2 SRD 1 - Guide to Obtaining AAR Refuelling Clearances & Compatibility Certification

  10. Determining the amounts of urea and glucose in urine of patients with renal complications from diabetes mellitus and hypertension by near-infrared Raman spectroscopy

    Science.gov (United States)

    Bispo, Jeyse A. M.; Silveira, Landulfo; Vieira, Elzo E. d. S.; Fernandes, Adriana B.

    2013-02-01

    Diabetes mellitus and hypertension diseases are frequently found in the same patient, which if untreated predispose to atherosclerotic and kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through dispersive near-infrared Raman spectroscopy. Urine samples were collected from patients with diabetes and hypertension but no complications (LG), high degree of complications (HG), and control ones: one fraction was submitted to biochemical tests and another one was stored frozen (-20°C) until spectral analysis. Samples were warmed up and placed in an aluminum sample holder for Raman spectra collection using a dispersive spectrometer (830 nm wavelength, 300 mW laser power and 20 s exposure time). Spectra were then submitted to Principal Components Analysis. The PCA loading vectors 1 and 3 revealed spectral features of urea/creatinine and glucose, respectively; the PCA scores showed that patients with diabetes/hypertension (LG and HG) had higher amount of glucose in the urine compared to the normal group (p diabetes/hypertension (p diabetes/hypertension, can lead to early diagnostic information of complications and a possible disease prognosis in the patients where no complications from diabetes and hypertension were found.

  11. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Scheen, André J

    2014-03-01

    Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

  12. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  13. Endurance training inhibits insulin clearance and IDE expression in Swiss mice.

    Directory of Open Access Journals (Sweden)

    José M Costa-Júnior

    Full Text Available Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice.Mice were treadmill-trained for 4 weeks at 70-80% of maximal oxygen consumption (VO2 max for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot.Trained mice exhibited an increased VO2 max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT and the non-canonical (CaMKII-AMPK-ACC insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle.Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.

  14. The Kidney's role in glucose balance following partial hepatectomy.

    Science.gov (United States)

    Jones, C E; Koshibu, K; DeCambre, M; Gerich, J E; Bessey, P Q; Krusch, D A

    1998-10-01

    It has long been believed that the liver is the major contributor to glucose balance during fasting and stressful situations. Recently, investigators have implicated the kidney as having a significant contribution to systemic glucose appearance. We studied the relative contributions of the kidney and liver to glucose homeostasis in fasted nonoperated, sham-operated, and 70% hepatectomized rats. Systemic glucose appearance, renal glucose release and uptake, and hepatic glucose release were determined by glucose balance and isotopic dilution techniques. Systemic glucose appearance remained unchanged following hepatectomy. There was a significant output of glucose by the kidney in all groups, accounting for >50% of total glucose appearance. Despite the kidney's appreciable contribution to circulating glucose in the postabsorptive state, renal glucose release was not increased in the hepatectomized rats compared to controls. Total glucose appearance was maintained following hepatectomy by an increase in hepatic glucogenesis. There was a significant increase in the rate of hepatic glucose release from resected rats when normalized to gram of remaining liver (P < 0.001). Despite the substantial amount of renal glucose output in the postabsorptive state, preservation of glucose balance following 70% hepatectomy is accomplished by adaptation in hepatic glucose output.

  15. Effects of "in vivo" administration of baclofen on rat renal tubular function.

    Science.gov (United States)

    Donato, Verónica; Pisani, Gerardo Bruno; Trumper, Laura; Monasterolo, Liliana Alicia

    2013-09-05

    The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01-1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone.

  16. 30 CFR 18.24 - Electrical clearances.

    Science.gov (United States)

    2010-07-01

    ... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure...

  17. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  18. Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2

    DEFF Research Database (Denmark)

    Geertsen, P F; von der Maase, H; Olsen, Niels Vidiendal

    1998-01-01

    ) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used....../82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor...... effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment....

  19. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  20. The kidneys play a central role in the clearance of rhGH in rats.

    Science.gov (United States)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads; Fels, Johannes Josef; Lykkesfeldt, Jens; Agersø, Henrik

    2016-04-30

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

  1. Long-term fructose intake: biochemical consequences and altered renal histology in the male rat.

    Science.gov (United States)

    Kizhner, Tali; Werman, Moshe J

    2002-12-01

    The use of fructose as a pure sugar has considerably increased in the last 3 decades, especially as a sweetener in carbonated beverages. Our previous studies showed that long-term fructose intake adversely affected several age-related metabolic parameters. The purpose of the present study was to compare the consequences of long-term fructose intake with those of glucose or sucrose on renal morphology and on several biochemical parameters used to estimate renal function. Male rats were fed a commercial diet for 16 months, and had free access either to water (control) or to 250 g/L solutions of fructose, glucose, or sucrose. Fructose-drinking rats exhibited higher liver weights compare to the other dietary groups. Control rats excreted significantly less urinary output than all sugar groups, which did not differ from each other. No differences were observed in fasting plasma fructose, glucose, and creatinine levels, or in urinary glucose levels. Fructose consumption resulted in elevated urinary fructose levels, higher creatinine clearance, and marked proteinuria. The tested sugars had influence on the molecular weight distribution of urinary proteins in the ranges of 10 to 16, 25 to 35, and 75 to 85 kd. Histological examination revealed that fructose consumption led to the formation of foci of cortical tubular necrosis with chronic inflammatory infiltrate, accumulation of tubular hyaline casts, thickening of the Bowman's capsule, mesangial thickening due to collagen deposits, and the occurrence of hemosiderin in tubular cells. These data suggest that fructose has a negative impact on kidney function and morphology. Further research is required to elucidate the precise mechanisms by which long-term fructose consumption hampers renal metabolism.

  2. Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

    Science.gov (United States)

    Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

    2017-02-01

    Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4th hour of PET as slow transporter ( 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p 2 vs. 48.4 ± 14.0 L/week/1.73 m2, p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
.

  3. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. (Karolinska Hospital, Stockholm (Sweden))

    1990-11-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

  4. Measuring biomarkers of acute kidney injury during renal replacement therapy: wisdom or folly?

    Science.gov (United States)

    Ostermann, Marlies; Forni, Lui G

    2014-06-19

    Early data are now appearing relating to the measurement of biomarkers of acute kidney injury during renal replacement therapy. These data go some way in describing the clearance of these molecules during renal support. Understanding the potential clearance, or otherwise, of these proteins may lead to directing our therapies in the future particularly with regard to cessation of renal support. We describe a recent study which has provided data that may aid in addressing this issue.

  5. Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats.

    Science.gov (United States)

    Bertuzzi, A; Mingrone, G; De Gaetano, A; Gandolfi, A; Greco, A V; Salinari, S

    1997-07-01

    Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3.9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0.72 ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17.8 mumol/min per kg BW corresponding to 123.7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D[-U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2.3 mmol/kg BW) and total-body rate of disappearance (82.1 mumol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36.7 mumol/min per kg BW and the extent of recycling appeared to be negligible.

  6. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, R.E.; Hjelle, J.T.; Mahoney, C.; Deftos, L.J.; Lisker, W.; Kato, P.; Rabkin, R.

    1988-04-01

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

  7. Renal calculus disease.

    Science.gov (United States)

    Schulsinger, D A; Sosa, R E

    1998-03-01

    We have seen an explosion in technical innovations for the management of urolithiasis. Today, the endourologist possesses an assortment of minimally invasive tools to treat renal stones. Most patients receive fast, safe and effective treatment in the outpatient setting. Despite the many technical advances, however, anatomical malformations and complex stones still provide significant challenges in diagnosis, access to a targeted stone, fragmentation, and clearance of the resulting fragments. This review examines a variety of urinary stone presentations and treatment strategies for cost-effective management.

  8. 血糖波动与持续性高血糖对糖尿病大鼠肾脏病理改变及IV型胶原表达的影响%Effect of blood glucose fluctuation and the sustained high blood glucose on renal pathological change and collagen IV expression in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    王环君; 王爱民; 雷闽湘; 廖洁; 胡维

    2013-01-01

    目的:观察血糖波动与持续性高血糖对糖尿病大鼠肾脏病理改变及IV型胶原(Col IV)表达的影响。方法:将60只SD雄性大鼠随机分为正常组和模型组,正常组大鼠喂以普通饲料,模型组大鼠高糖高脂饲料喂养6周后予以小剂量链脲佐菌素(STZ,30 mg/kg)皮下注射制造糖尿病大鼠模型。再将糖尿病组大鼠随机分为持续性高血糖组和血糖波动组,其中血糖波动组给予每日两次皮下注射胰岛素人为诱导血糖波动。3个月后将大鼠剖腹取出肾,行HE染色、PAS染色、Col IV免疫组织化学及Western印迹检测。结果:与正常组大鼠比较,模型组大鼠肾小球体积增大、毛细血管内皮细胞基底膜增厚、系膜基质增多、肾小球球囊腔扩张,肾小管体积增大、肾小管管腔扩张、上皮细胞基底膜增厚,肾小球通透性增强,肾脏病理形态改变明显;肾肥大指数增加、肾小球硬化指数增加、Col IV表达量明显增加(P Methods:hTe 60 male Sprague-Dawley (SD) rats were randomly assigned into a normal control group (NC) and a model group (DM). hTe rats in the normal control group were fed with normal diet, while the rats in the model group were fed with high-sucrose-high-fat diet for 6 weeks. Atfer that,streptozocin (STZ, 30 mg/kg) was injected to induce diabetic model. The model group was then randomly divided into 2 subgroups:a sustained high blood glucose group and a fluctuation blood glucose group (animals in the latter group were subcutaneously injected with insulin twice daily). Rats were sacriifced atfer 3 months and kidney tissues were dissected for HE and PAS staining, Col IV immunohistochemistry and Western blot. Results:Compared with the normal control group, the renal glomeruli and capillary basal membrane in the diabetic rats was getting larger and thicker, respectively;the capsular space and ground substance was extended and increased, respectively;the volume of

  9. Determining vancomycin clearance in an overweight and obese population.

    Science.gov (United States)

    Leong, Julie V B; Boro, Maureen S; Winter, Michaele

    2011-04-01

    Two methods of calculating vancomycin clearance were compared to determine the best body weight measure to use when dosing vancomycin for overweight and obese patients. Hospitalized veterans weighing more than 120% of their ideal body weight (IBW) with serum vancomycin concentrations (SVCs) drawn between January 1, 2003, and June 30, 2005, were eligible for study inclusion. Exclusion criteria included weight of more than 300% the IBW, unstable renal function, dialysis, uncertain vancomycin dosing or sampling times, and distribution-phase sampling. Data from January 1 through December 31, 2003 (phase 1) determined the best-fit weight for vancomycin clearance for the Leonard and Boro method. The bias and precision of the modified Leonard and Boro method using the best-fit weight for vancomycin clearance were then compared with those of the Rushing and Ambrose method for predicting SVCs from January 1, 2004, through June 30, 2005 (phase 2). Forty-eight patients were included in phase 1, with 67 SVCs for analysis. During phase 1, adjusted body weight (ABW), using the Leonard and Boro method, was superior in predicting vancomycin clearance and the resultant SVCs. A total of 96 patients were included in phase 2 of the study, with 160 SVCs for analysis. The modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting vancomycin clearance. Use of ABW proved to be superior compared with total body weight when estimating vancomycin clearance in overweight and obese patients. While there was no difference in bias between methods, the modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting SVCs when dosing vancomycin for obese patients.

  10. 33 CFR 117.47 - Clearance gauges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Clearance gauges. 117.47 Section... OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for... specify otherwise for particular drawbridges, clearance gauges shall be designed, installed,...

  11. 30 CFR 57.11010 - Stairstep clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 57.11010 Section 57.11010... Escapeways Travelways-Surface and Underground § 57.11010 Stairstep clearance. Vertical clearance above stair... to indicate an impaired clearance....

  12. 30 CFR 56.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance...

  13. 30 CFR 56.11010 - Stairstep clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 56.11010 Section 56.11010... Stairstep clearance. Vertical clearance above stair steps shall be a minimum of seven feet, or suitable warning signs or similar devices shall be provided to indicate an impaired clearance....

  14. 30 CFR 57.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008... Escapeways Travelways-Surface and Underground § 57.11008 Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance shall be conspicuously marked....

  15. 14 CFR 25.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most...

  16. 32 CFR 154.16 - Security clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section 154.16... clearance. (a) General. (1) The authorities designated in paragraph A, Appendix E are the only authorities authorized to grant, deny or revoke DoD personnel security clearances. The granting of such clearances...

  17. 28 CFR 524.74 - Activities clearance.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... clearance. (a) Except as provided for in paragraph (b) of this section, the Warden is the clearance... Security cases. Central Office Inmate Monitoring Section staff shall be the clearance authority on...

  18. Hypogonadism and renal failure: An update

    Directory of Open Access Journals (Sweden)

    Nannan Thirumavalavan

    2015-01-01

    Full Text Available The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  19. Hypogonadism and renal failure: An update.

    Science.gov (United States)

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  20. Establishment and use of surgical rat models for assessment of organ specific in vivo clearance.

    Science.gov (United States)

    Vestergaard, Bill

    2016-06-01

    Knowledge of clearance plays a key role in the development of new drug entities, especially in the development of improved analogues for treatment of chronic conditions. Improved pharmacokinetic properties can be used to increase dosing interval and thereby improve patient compliance. This will lead to improved treatment outcome or decreased risk of treatment failure when treating chronic conditions. Therefore, animal models for assessment of organ-specific clearance are of great value in preclinical drug development. These models can be used to obtain insights into the relative importance of a clearance organ and thereby guide drug design of new analogues in early drug discovery. The current PhD project was undertaken to explore surgical in vivo models, which could be used in the assessment of the relative importance of major clearance organs. It was the aim of the PhD project to establish and validate both a nephrectomy model and a hepatectomy model as tools to investigate relative importance of renal and hepatic clearance. Furthermore, the project aim was to investigate renal clearance of rFVIIa and rhGH using a nephrectomy model in rats. The thesis is composed of a short theoretical background, a literature review, two papers based on experimental work as well as experimental work not included in the papers. Chapter one is an introduction with the specific aims and hypotheses. The chapters from two to five contain theoretical background of the clearance concept, anatomical and physiological description of clearance organs and a brief overview of potential clearance models including in vivo models. Chapters six through nine highlight the experimental work with the results obtained during the PhD project. Lastly, the chapters from ten to twelve contain a general discussion, conclusion and perspectives of the current thesis. Paper I "Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics" provides a literature review of animal

  1. Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones.

    Science.gov (United States)

    Blum, R A

    1992-04-06

    Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles. Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency. Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver. The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin. The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion. Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments. For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min. This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin. There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution.

  2. Effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Lubin Xu

    2017-06-01

    Full Text Available Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR and/or urine albumin/creatinine ratio (ACR changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD, −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23] or in patients with chronic kidney disease (CKD (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]. SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54], and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]. Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06], but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]. Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

  3. The rebirth of interest in renal tubular function.

    Science.gov (United States)

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate.

  4. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes

    NARCIS (Netherlands)

    Heerspink, H. J. Lambers; de Zeeuw, D.; Wie, L.; Leslie, B.; List, J.

    2013-01-01

    Aims: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-l

  5. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes

    NARCIS (Netherlands)

    Heerspink, H. J. Lambers; de Zeeuw, D.; Wie, L.; Leslie, B.; List, J.

    2013-01-01

    Aims: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-l

  6. Impact of maximum Standardized Uptake Value (SUVmax evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT on survival for patients with advanced renal cell carcinoma: a preliminary report

    Directory of Open Access Journals (Sweden)

    Miura Takeshi

    2010-12-01

    Full Text Available Abstract Background In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT on survival for patients with advanced renal cell carcinoma (RCC. Methods A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. Results FDG uptake was detected in 230 of 243 lesions (94.7% excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0. The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614. The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012. This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively. Conclusions The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG-PET/CT. 18F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making.

  7. Radionuclide evaluation of renal artery dilatation

    Energy Technology Data Exchange (ETDEWEB)

    Born, M.L.; Gerlock, A.J. Jr.; Goncharenko, V.; Hollifield, J.W.; MacDonell, R.C. Jr.

    1981-01-01

    Radionuclide studies were used in three patients to evaluate renal perfusion and function within 24 hours following transluminal dilatation. In one patient, technetium-99 m pertechnetate showed good renal perfusion one and 12 hours after a post-dilatation arteriogram had shown a renal artery intimal defect. Improved clearance of iodine-131 ortho-iodohippurate from the blood demonstrated an increase in renal function 18 hours following dilatation of a stenosis at a renal allograft anastomosis in the second patient, while technetium-99 m-labeled DTPA showed an improved total glomerular filtration rate 24 hours after dilatation of a saphenous vein bypass graft in the third patient. It was concluded that renal radionuclide studies are of benefit in evaluating patients in the immediate post-dilatation period.

  8. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of (3H)PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of (3H)6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment.

  9. 不同检测仪器测定血清肾功、血糖、淀粉酶结果比对分析%Different detecting instrument determination of renal function, blood glucose, serum amylase results comparison analysis

    Institute of Scientific and Technical Information of China (English)

    王立平; 闫建燕

    2015-01-01

    目的:观察不同检测仪器对患者的血清肾功、血糖、淀粉酶检测,就临床应用价值及结果进行分析。方法:回顾选取40例我院2013年5月—2014年5月期间收治的患者,依据美国临床最新实验室委员会的标准,每日抽取患者的即时血清,根据不同检测仪器就患者的血清肾功、血糖、淀粉酶进行平行测定。以美国临床实验修改正案CLIA,88所建议的标准作为本次研究的标准,对比分析不同检测仪器测定下的血清肾功、血糖、淀粉酶结果误差情况来判定结果的可比性,结果存在差异。结果:本次实验患者在经两种检测仪器所检测结果后发现具有可比性与相关性,结果不具有统计学意义。结论:本次研究在两种检测仪器测定下结果不具有统计学意义。为患者诊断提供依据并且节省因病情不确定而浪费的治疗时间,值得推广及应用。%ObjectiveObserve different detecting instrument for patients with renal function, blood glucose, serum amylase test value of clinical application, and analyze the results.Methods From 40 cases in May 2013 to May 2014 treated patients, on the basis of the latest clinical laboratory commission standards, daily extraction in patients with serum immediately, according to the different detecting instrument in patients with renal function, blood glucose, serum amylase for parallel determination.Results This experiment patients in the two kinds of testing instruments and found the test result comparable with correlation, the result is not statistically significant. Conclusions The study results under two kinds of testing instrument measurement is not statistically significant. Provide the basis for the diagnosis and save waste because of the uncertain condition, treatment time, worthy of popularization and application.

  10. [Amylase-creatinine clearance ratios in burned patients (author's transl)].

    Science.gov (United States)

    Minaire, Y; Marichy, J; Forichon, J; Motin, J

    1978-09-01

    The amylase/creatinine clearance ratio (ACCR) has been examined every 3 days, in 34 burned patients during the 20 days following the accident. This ratio was often abnormal since it was found increased at least on one occasion, in 75% of these patients, to be compared with 23 and 13% for amylase in serum and urine respectively. In another group of 9 burned patients, the ACCR was monitored for time-period between 10 to 52 days. It was observed that a high frequency in increased ACCR was associated with a fatal outcome. Finally simultaneous measurements of ACCR and of the beta2 microglobulin/creatinine clearance ratio (MCCR) showed that increased ACCR were statistically associated with increased MCCR suggesting a decreased renal tubular reabsorption of low molecular weight proteins in these burned patients.

  11. Specificity of increased amylase to creatinine clearance ratio in acute pancreatitis.

    Science.gov (United States)

    Lankisch, P G; Koop, H; Otto, J; Oberdieck, U; Winckler, K; Wolfrum, D I

    1977-01-01

    The amylase to creatinine clearance ratio was found to be normal in 11 of 33 patients with acute pancreatitis. The ratio was elevated in 10 of 19 patients with renal insufficiency. Thus, it does not seem to be a specific index in the diagnosis of acute pancreatitis.

  12. 反式曲马朵及其活性代谢产物反式氧去甲基曲马朵肾脏清除的立体选择性%Stereoselectivity in renal clearance of trans-tramadol and its active metabolite, trans-O- demethyltramadol

    Institute of Scientific and Technical Information of China (English)

    刘会臣; 张熙洁; 杨燕燕; 王娜; 侯艳宁

    2002-01-01

    AIM: To study the stereoselectivity in renal clearance of trans-tramadol and its active metabolite, trans-O-demethyltramadol. METHODS: The right kidneys were isolated from male SD rats and perfused with 100 mL of perfusate medium containing trans-tramadol 300μg/L or trans-O-demethyltmmadol 50 μg/L.After perfusion, the concentrations of the enantiomers of trans-tramadol and trans-O-demethyltramadol in the perfusate and urine were determined by high performance capillary electrophoresis. The enantiomeric ratios were calculated. RESULTS: After the kidneys being perfused with trans-tramadol hydrochloride, the concentration of ( + )-trans-tramadol was higher than that of (-)-trans-tramadol, and the concentration of ( + )-trans-O-demethyltramadol was lower than that of ( - )-trans-O-demethyltramadol in the perfusate; meanwhile,(+)-trans-tramadol was more than (-)-trans-tramadol, and ( + )-trans-O-demethyltramadol was less than (-)-trans-O-demethylwamadol in the urine.After the kidneys being perfused with trans-O-demethyltramadol, the concentration of ( + )-trans-O-demethyltramadol was lower than that of ( - )-trans-O-dkenethyltramadol in the perfusate, and ( + )-trans-O-demethyltramadol was more than ( - )- trans- O-demethyltramadol in the urine. CONCLUSION: Therenal clearance of trans-tramadol was stereoselective.The O-demethylation of trans-tramadol was stereoselective in the kidneys, ( - )-trans-tramadol being preferentially metabolized. The renal clearance of trans-O-demethyltramadol was also stereoselective, the ( + )-enantiomer being preferentially cleared into the urine.%目的:研究反式曲马朵及其活性代谢物反式氧去甲基曲马朵肾脏清除的立体选择性.方法:取雄性SD大鼠的右肾,分别以含反式曲马朵(300 μg/L)或反式氧去甲基曲马朵(50 μg/L)的灌流液(100 mL)进行灌流;利用高效毛细管电泳法测定灌流后灌流液、尿液中反式曲马朵及反式氧去甲基曲马朵对映体的浓度,并计算对映

  13. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.

    Science.gov (United States)

    Nie, Huibin; Xue, Xia; Liu, Gang; Guan, Guangju; Liu, Haiying; Sun, Lina; Zhao, Long; Wang, Xueling; Chen, Zhixin

    2016-01-01

    Nitroalkene derivative of oleic acid (OA-NO2), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO2 in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO2 (1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO2 promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO2 inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22(phox) up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO2 reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.

  14. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

    DEFF Research Database (Denmark)

    Gülberg, V; Møller, S; Henriksen, Jens Henrik Sahl

    2000-01-01

    .05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; pUrinary CNP was found to be inversely related to urinary...... homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients...... with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate...

  15. Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension.

    Science.gov (United States)

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1996-02-22

    The long-term effects of indapamide or hydrochlorothiazide on blood presssure and renal function were examined in patents with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  16. Lactate clearance in cardiorespiratory emergency

    Directory of Open Access Journals (Sweden)

    Serena Greco

    2007-08-01

    Full Text Available Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8 (APACHE II score 19,0 ± 4,1, were included in the study. Blood lactate concentration was read at admission and after 2, 6 and 24 hours. We evaluated mortality at seven days and the use of orotracheal intubation (patients with negative outcome vs. discharge or transfer to a non-emergency ward with subsequent discharge (patients with negative outcome. Lactate concentration at admission was 4,6 ± 2,5 mmol/l; lactate clearance (% at 2 hours was 40,4 ± 32,1 in patients with a positive outcome and –8,3 ± 5,0 in patients with a negative outcome (p < 0,05. Lactate clearance at 2 hours < 25% is correlated to a negative outcome with an 84,2% sensitivity and a 79,2% specificity. The positive predictive value was 61,5% and the negative predictive value was 92,2%. Systematic lactate clearance monitoring can be used in cases of acute cardiorespiratory insufficiency to identify patients with a high risk of negative outcome. In our study, low clearance at two hours was associated with an increase in mortality and/or the need for orotracheal intubation. Conversely, a clearance at two hours of > 25% in most cases confirms the therapeutic strategy undertaken. Serial evaluation of blood lactate concentration may therefore be useful in guiding treatment strategies.

  17. Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

    1986-05-01

    Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the (6-/sup 3/H)glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 ..mu..U/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.

  18. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  19. A review of renal protection strategies

    African Journals Online (AJOL)

    Intravenous fluids are briefly mentioned as they relate to renal function. ... define AKI as more than a 50% decrease in creatinine clearance. This provides a ... intravenous (IV) fluid loads during anaesthesia is very different to that in the awake ...

  20. Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of (51) Cr-EDTA.

    Science.gov (United States)

    Kiss, Katalin; Molnár, Miklós; Söndergaard, Sören; Molnár, Gyula; Ricksten, Sven-Erik

    2016-06-03

    We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of (51) Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg(-1) body weight (150 mg ml(-1) ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for (51) Cr-EDTA was 59·7 ± 18·8 ml min(-1) . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min(-1) and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min(-1) , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min(-1) . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and (51) Cr-EDTA for the assessment of GFR.

  1. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  2. Re-entry flight clearance

    NARCIS (Netherlands)

    Juliana, S.

    2006-01-01

    The objective of the research was to identify and evaluate promising mathematical techniques for re-entry flight clearance. To fulfil this objective, two mathematical methods were investigated and developed: μ analysis for linear models and interval analysis for both linear and non-linear model

  3. Comparison of glomerular filtration rates by dynamic renal scintigraphy and dual-plasma sample clearance method in diabetic nephropathy%肾动态显像法与双血浆法测定糖尿病肾病患者GFR的比较

    Institute of Scientific and Technical Information of China (English)

    解朋; 黄建敏; 潘莉萍; 刘晓梅; 魏玲格; 高建青

    2010-01-01

    目的 以双血浆法测得的肾小球滤过率(GFR)为参考标准,评价99Tcm-DTPA肾动态显像法测得的糖尿病肾病患者GFR的可靠性及准确性.方法 选择46例确诊为糖尿病肾病的患者,分别采用肾动态显像法和双血浆法测定其GFR(GFR肾动态法和GFR双血浆法).用配对t检验分析经体表面积标准化(1.73 m-2)的GFR肾动态法与GFR双血浆法间的差异有无统计学意义,并行相关性分析.结果 46例糖尿病肾病患者的GFR肾动态法范围为11.87~107.00 ml·min-1,均值为(51.08±26.78)ml·min-1;GFR双血浆法范围为4.17~118.56ml·min-1,均值为(44.06±29.43)ml·sin-1;两者间差异有统计学意义(t=4.209,P=0.000),前者略高于后者,且两者呈显著正相关(r=0.923,P=0.000),直线回归方程为GFR双血浆法=1.015×GFR肾动态法-7.773(F=254.656,P=0.000).结论 GFR肾动志法与GFR双血浆法的差异有统计学意义,对于糖尿病肾病患者尚不能用GFR肾动态法代替GFR双血浆法;但肾动态显像法能够较准确评价糖尿病肾病患者的肾滤过功能.%Objective To evaluate the accuracy of renal scintigraphy for the estimation of glomerular filtration rates (dGFR) in patients with diabetic nephropathy as compared to the conventional dual-plasma sample clearance method (pscGFR). Methods Forty-six patients with diabetic nephropathy underwent both dynamic renal scintigraphy and dual-plasma sample measurement after 99Tcm-DTPA injection. Paired student t-test and correlation analysis were performed to compare dGFR and pscGFR (normalized to body surface area,1.73 m-2). Results The mean dGFR was higher than mean pscGFR ((51.08±26.78)ml·min-1vs (44.06±29.43)ml·min-1,t=4.209,P=0.000). The dGFR correlated with pscGFR ( r=0.923,P=0.000) linearly (regression equation:pscGFR=1.015×dGFR-7.773,F=254. 656,P=0.000).Conclusions dGFR correlated well with pscGFR. Although it could not absolutely replace the latter in patients with diabetic nephropathy,dGFR could

  4. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  5. Over-estimation of glomerular filtration rate by single injection [51Cr]EDTA plasma clearance determination in patients with ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Brøchner-Mortensen, J; Malchow-Møller, A;

    1980-01-01

    The total plasma (Clt) and the renal plasma (Clr) clearances of [51Cr]EDTA were determined simultaneously in nine patients with ascites due to liver cirrhosis. Clt (mean 78 ml/min, range 34-115 ml/min) was significantly higher than Clr (mean 52 ml/min, range 13-96 ml/min, P .... To assess glomerular filtration rate in presence of ascites, the renal plasma clearance of [51Cr]EDTA should be used instead of the total plasma clearance....

  6. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  7. Combination of crystalloid (glucose) and colloid (icodextrin) osmotic agents markedly enhances peritoneal fluid and solute transport during the long PD dwell.

    Science.gov (United States)

    Freida, Philippe; Galach, Magda; Divino Filho, Jose C; Werynski, Andrzej; Lindholm, Bengt

    2007-01-01

    Fluid and sodium removal is often inadequate in peritoneal dialysis patients with high peritoneal solute transport rate, especially when residual renal function is declining. We studied the effects of using simultaneous crystalloid (glucose) and colloid (icodextrin) osmotic agents on the peritoneal transport of fluid, sodium, and other solutes during 15-hour single-dwell exchanges using 3.86% glucose, 7.5% icodextrin, and a combination fluid with 2.61% glucose and 6.8% icodextrin in 7 prevalent peritoneal dialysis patients with fast peritoneal solute transport rate. The combination fluid enhanced net ultrafiltration (mean 990 mL) and sodium removal (mean 158 mmol) compared with 7.5% icodextrin (mean net ultrafiltration 462 mL, mean net sodium removal 49 mmol). In contrast, the 3.86% glucose-based solution yielded negligible ultrafiltration (mean -85 mL) and sodium removal (mean 16 mmol). The combination solution resulted in significantly improved urea (+41%) and creatinine (+26%) clearances compared with 7.5% icodextrin. A solution containing both crystalloid (glucose 2.61%) and colloid (icodextrin 6.8%) osmotic agents enhanced fluid removal by twofold and sodium removal by threefold compared with 7.5% icodextrin solution during a dwell of 15 hours, indicating that such a combination solution could represent a new treatment option for anuric peritoneal dialysis patients with high peritoneal solute transport rate.

  8. Effects of glucose and amino acid infusion on glucose turnover in insulin-resistant obese and type II diabetic patients.

    Science.gov (United States)

    Tappy, L; Acheson, K; Normand, S; Pachiaudi, C; Jéquier, E; Riou, J P

    1994-04-01

    Glucose turnover was assessed from [6,6-2H]glucose and [U-13C]glucose dilution analysis in six lean nondiabetic subjects, six obese patients with normal glucose tolerance, and six obese patients with non-insulin-dependent diabetes mellitus (NIDDM) during sequential infusions of glucose (13.9 mumol/kg fat-free mass [FFM]/min) and glucose+amino acid (4.2 mg/kg FFM/min). Cori cycle activity was assessed from the difference between glucose turnover obtained from [6,6-2H]glucose and [U-13C]glucose. During infusion of glucose alone, total glucose turnover was increased by 70% in obese NIDDM patients. Amino acid infusion decreased glucose concentrations by 0.8, 0.5, and 1.8 mmol/L in controls, obese patients, and NIDDM patients, respectively. This decrease in glycemia occurred despite an increase in glucose turnover in lean and obese nondiabetic subjects, and was due to an increased metabolic clearance rate (MCR) of glucose. In NIDDM patients the MCR of glucose was unchanged, and the decrease in glycemia was explained by a diminution in hepatic glucose output. Glucose turnover obtained by [6.6-2H] dilution analysis exceeded significantly the values obtained by dilution analysis in obese subjects and obese NIDDM patients, but not in controls. This indicates an increased Cori cycle activity in these patients.

  9. Renal amyloidosis in a drug abuser.

    Science.gov (United States)

    Tan, A U; Cohen, A H; Levine, B S

    1995-03-01

    Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.

  10. A pharmacokinetic study of roxatidine acetate in chronic renal failure.

    Science.gov (United States)

    Lameire, N; Rosenkranz, B; Maass, L; Brockmeier, D

    1988-01-01

    The pharmacokinetics of a single oral dose of roxatidine acetate 150 mg were studied in 31 patients with varying degrees of chronic renal failure. The patients were divided into 5 groups according to their creatinine clearance (Clcr): controls (Clcr 94.5 +/- 13.9 ml/min; n = 6); mild chronic renal failure (Clcr 47 +/- 6 ml/min; n = 4); moderate chronic renal failure (Clcr 27.3 +/- 3.1 ml/min; n = 4); severe chronic renal failure (Clcr 12.8 +/- 1.4 ml/min; n = 5) and uraemia (Clcr 6.6 +/- 0.6 ml/min; n = 12). Serum and urine samples were analysed with capillary gas chromatography to measure the salt of the desacetyl metabolite of roxatidine acetate (roxatidine). The terminal half-life was 6.02 +/- 0.31 hours in controls and 7.35 +/- 0.57, 9.3 +/- 0.83, 14.6 +/- 3.7 and 18.10 +/- 2.77 hours, respectively, in the 4 other groups, with progressively decreasing creatinine clearance. Maximum serum concentration and time to maximum serum concentration rose from 816 +/- 75 ng/ml and 2.08 +/- 0.22 hours, respectively, in controls to 1364.7 +/- 156 ng/ml and 4.05 +/- 0.47 hours, respectively, in uraemic patients. Relative total clearance progressively decreased with decreasing glomerular filtration rate (GFR) [from 353.6 +/- 26 ml/min in controls to 90.31 +/- 12.2 ml/min in patients with uraemia]. Renal clearance decreased from a control of 243.9 +/- 56 ml/min to 12.32 +/- 0.18 ml/min in uraemic patients. A linear correlation between creatinine clearance and both relative total clearance and renal drug clearance was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  12. JNK在血糖波动的糖尿病大鼠肾小管上皮细胞凋亡中的作用%The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose

    Institute of Scientific and Technical Information of China (English)

    郝卯林; 戴雍月; 倪世容; 汪大望; 李素娟; 金可可

    2012-01-01

    Objective: To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rate with fluctuant high blood glucose. Methods: Healthy SD rats were randomly divided into 3 groups: normal control group(A), stable high Hood glucose gnwp(B) and fluctuant high Mood glucose group(C). Diabetic rats were induced by inbaperitoneal injection of streptozotocin( SIZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The supenndde dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry.The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western bint. Apoptosis was assessed by terminal deoxynucleotidyl Iransferase-mediated dUTP nick-end labelling (TUNEL). Results: After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group. Condition: Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.%目的:探讨血糖波动的糖尿病大鼠发生肾小管上皮细胞凋亡的信号转导机制.方法:健康SD大鼠随机分为正常对照组(A)、糖尿病稳定高血糖组(B)和糖尿病波动高血糖组(C),采用链脲佐菌素(STZ)65 mg/kg腹腔注射诱发糖尿病,血糖波动组每天定时腹腔注射速效胰岛素,并错时给予葡萄糖,造成一天中血糖浓度大幅度波动模型.制模12周后,采用比色法检测肾组织匀浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA

  13. 49 CFR 192.325 - Underground clearance.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Underground clearance. 192.325 Section 192.325... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at least 12 inches (305 millimeters) of clearance from any other underground structure not associated with...

  14. Detecting reduced renal function in children

    DEFF Research Database (Denmark)

    Andersen, Trine Borup; Jødal, Lars; Erlandsen, Erland J

    2013-01-01

    Background The aim of this study was to compare the ability of renal indicators [serum creatinine (SCr), cystatin C (SCysC)] and glomerular filtration rate (GFR)-models to discriminate normal and reduced renal function. As a single cut-off level will always lead to false classifications, we propose...... function was defined as a GFR ofmodels were compared for their ability to correctly classify renal function as normal or reduced. Cut-off levels were determined so as to give 99 % certainty outside the gray zone...... using two cut-off levels, dividing renal function into normal or reduced, with an intermediate "gray zone" of indeterminable results.Methods Glomerular filtration rate was measured by plasma clearance of 51Cr-EDTA (13.7–147.4 mL/min/1.73 m2) in 119 children (age range 2.3–14.9 years).Reduced renal...

  15. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients

    DEFF Research Database (Denmark)

    Hansen, J M; Løkkegaard, H; Høy, Carl-Erik

    1995-01-01

    volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR...... and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium...

  16. Measuring residual renal function in dialysis patients: can we dispense with 24-hour urine collections?

    Science.gov (United States)

    Davenport, Andrew

    2016-05-01

    Residual renal function is associated with improved survival and quality of life for dialysis patients. Whereas residual renal function is monitored in peritoneal dialysis patients, many hemodialysis centers simply concentrate on achieving dialyzer urea clearance targets. Accurately quantifying residual renal function from urine collections is arduous. Thus, there is a clinical need to develop alternative methods of assessing residual renal function based on serum testing, especially for patients receiving less than thrice weekly dialysis.

  17. The use of lithium clearance measurements as an estimate of glomerulo-tubular function.

    Science.gov (United States)

    Whiting, P H

    1999-01-01

    Lithium clearance measurements are based on the observation that lithium undergoes isoosmotic reabsorption in the proximal renal tubule to the same extent as salt and water, but undergoes neither reabsorption nor secretion elsewhere in the nephron. Consequently, lithium clearance values estimate the delivery of isoosmotic fluid to the loop of Henle and hence provide an assessment of proximal tubular reabsorption of isoosmotic fluid. If sodium clearance and urinary flow rate are also measured, then this allows the derivation of a number of parameters relating to both the absolute and relative renal handling of isoosmotic fluid in the proximal and distal regions of the kidney. Consequently, lithium clearance techniques can be used in both experimental and clinical studies to evaluate glomerulo-tubular function and provide information regarding the handling of sodium and water by the proximal and distal nephron in both health and disease. The use of lithium clearance measurements in the assessment of glomerulo-tubular function in patients treated with rIL2 for colorectal cancer is described and its application to both drug-induced toxicity and other disease states discussed.

  18. Renal Glycosuria without Hyperglycemia in Cyclosporine-Treated Rats

    Directory of Open Access Journals (Sweden)

    Chang Hwa Lee

    2012-06-01

    Conclusion: Glycosuria may occur without hyperglycemia in cyclosporine administration. We suggest that cyclosporine may decrease tubular reabsorption of glucose in renal tubular epithelial cells, and then glycosuria could be induced by the altered glucose transporter expressions. We will analyze the glucose transporters in proximal tubule of rat kidney.

  19. Changes in renal tri-iodothyronine and thyroxine handling during fasting

    NARCIS (Netherlands)

    E.J. Rolleman; G. Hennemann; H. van Toor (Hans); C.H.H. Schoenmakers (Christian); E.P. Krenning (Eric); M. de Jong (Marion)

    2000-01-01

    textabstractOBJECTIVE: Liver handling of thyroid hormones (TH) has been known to alter significantly during fasting. This study investigates whether renal handling of TH is also changed during fasting. METHODS: We measured urinary excretion rates and clearances of free

  20. Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Kanstrup, I L

    1993-01-01

    , heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P

  1. Physiologically Based Pharmacokinetic Predictions of Tramadol Exposure Throughout Pediatric Life: an Analysis of the Different Clearance Contributors with Emphasis on CYP2D6 Maturation.

    Science.gov (United States)

    T'jollyn, Huybrecht; Snoeys, Jan; Vermeulen, An; Michelet, Robin; Cuyckens, Filip; Mannens, Geert; Van Peer, Achiel; Annaert, Pieter; Allegaert, Karel; Van Bocxlaer, Jan; Boussery, Koen

    2015-11-01

    This paper focuses on the retrospective evaluation of physiologically based pharmacokinetic (PBPK) techniques used to mechanistically predict clearance throughout pediatric life. An intravenous tramadol retrograde PBPK model was set up in Simcyp® using adult clearance values, qualified for CYP2D6, CYP3A4, CYP2B6, and renal contributions. Subsequently, the model was evaluated for mechanistic prediction of total, CYP2D6-related, and renal clearance predictions in very early life. In two in vitro pediatric human liver microsomal (HLM) batches (1 and 3 months), O-desmethyltramadol and N-desmethyltramadol formation rates were compared with CYP2D6 and CYP3A4 activity, respectively. O-desmethyltramadol formation was mediated only by CYP2D6, while N-desmethyltramadol was mediated in part by CYP3A4. Additionally, the clearance maturation of the PBPK model predictions was compared to two in vivo maturation models (Hill and exponential) based on plasma concentration data, and to clearance estimations from a WinNonlin® fit of plasma concentration and urinary excretion data. Maturation of renal and CYP2D6 clearance is captured well in the PBPK model predictions, but total tramadol clearance is underpredicted. The most pronounced underprediction of total and CYP2D6-mediated clearance was observed in the age range of 2-13 years. In conclusion, the PBPK technique showed to be a powerful mechanistic tool capable of predicting maturation of CYP2D6 and renal tramadol clearance in early infancy, although some underprediction occurs between 2 and 13 years for total and CYP2D6-mediated tramadol clearance.

  2. The Changes of renal excretion of uric acid in the subjects with different glucose tolerance conditions%肾脏尿酸排泄在不同糖耐量状态下的变化

    Institute of Scientific and Technical Information of China (English)

    韩学尧; 崔纪芳; 纪立农

    2013-01-01

    Objectives To investigate the changes of renal uric acid excretion in different stages of type 2 diabetes, and identify its relating facts, providing the evidence for individualized treatment for hyperuricemia in patients with type 2 diabetes. Methods 168 participants without history of diabetes were included in this study. OGTTs were conducted, the concentrations of uric acid, creatinine and albumin in spot morning fasting urine, concurrently the concentrations of uric acid and creatinine of fasting serum samples were determined. The fraction of uric acid excretion (FUE) and ratio of uric acid/creatinine (UUA/CRE) were calculated. Results No significant difference among three groups with normal OGTT(n= 61), pre-diabetes(impaired fasting glucose and /or impaired glucose tolerance, n=55) and diabetes(n=52) was observed; The subjects with male gender(P = 0. 007) , central obesity(P=0. 001) and hyperuricemia(P<0. 0001) have relatively low FUE and UUA/CRE compared with female gender, no central obesity and normal serum uric acid levels; Waist circumference was an independent fact associated with UUA/CRE(P<0.0001). 16 subjects with diabetes or pre-diabetes have hyperuricemia, of whom 12. 5% subjects have lower than 1% percentile of UUA/CRE obtained from 16 men and 29 women without hyperglycemia, hypertension and hyperuricemia. Conclusion Reduced renal excretion of uric acid play an important role in pathogenesis of hyperuricemia, and most patients with hyperglycemia and hyperuricemia might have combined excess product and low excretion of uric acid. Therefore, it's necessary to determine UUA/CRE before and after initiation of treatment for hyperuricemia in the patients with type 2 diabetes.%目的 研究T2DM自然病程的不同阶段肾脏尿酸排泄的变化,识别影响尿酸排泄的相关因素,为T2DM合并高尿酸血症个体化用药提供依据. 方法 收集168名无糖尿病病史的志愿者,行75 g OGTT,测定UA1b、Cr、Scr、UA与SUA,计算尿中尿

  3. Zinc dosing and glucose tolerance in humans

    Energy Technology Data Exchange (ETDEWEB)

    Greenley, S.; Taylor, M.

    1986-03-05

    Animal data suggest the existence of a physiologic relationship between glucoregulatory hormones and zinc metabolism. In order to investigate this proposed relationship in humans, they examined the effect of moderately elevated plasma zinc levels on blood glucose clearance. Eight women (24-37 yrs) served as subjects for the study. Fasted volunteers were tested under two experimental conditions (a) ingestion of 50 g D-glucose (b) ingestion of 25 mg zinc followed 60 min later by ingestion of 50 g D-glucose. Five ml venous blood was drawn into trace-metal-free, fluoride-containing vacutainer tubes prior to and 15, 30, 45, 60, 90, and 120 min after glucose ingestion. Plasma was analyzed for glucose and zinc; glycemic responses were quantified by computing areas under the curves and times to peak concentration. Their human data indicate varied glycemic responses to the acute elevation of plasma zinc: 4 subjects showed little apparent effect; 3 subjects marginally increased either the area under the curve or time to peak and 1 subject (classified as suspect diabetic in the non-zinc condition) showed marked improvement in glycemic response following zinc ingestion. Their preliminary results suggest that blood glucose clearance may be affected in some individuals by the acute elevation of plasma zinc.

  4. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    Science.gov (United States)

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  5. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    Science.gov (United States)

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  6. Hepatic insulin clearance is closely related to metabolic syndrome components.

    Science.gov (United States)

    Pivovarova, Olga; Bernigau, Wolfgang; Bobbert, Thomas; Isken, Frank; Möhlig, Matthias; Spranger, Joachim; Weickert, Martin O; Osterhoff, Martin; Pfeiffer, Andreas F H; Rudovich, Natalia

    2013-11-01

    Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome. Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated. Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97-1.31], P = 0.12, and HICISR 1.38 [0.88-2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92-1.36], P = 0.26, and HICISR 1.31 [0.74-2.33] P = 0.36), although point estimates reached no statistical significance. HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects.

  7. Dextran fractional clearance studies in acute dengue infection.

    Directory of Open Access Journals (Sweden)

    Julie Nguyen-Pouplin

    2011-08-01

    Full Text Available BACKGROUND: Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers. METHODOLOGY/PRINCIPAL FINDINGS: We carried out serial clearance studies in 15 young adult males with acute dengue and evidence of vascular leakage a during the phase of maximal leakage and b one and three months later, as well as in 16 healthy control subjects. Interestingly we found no difference in the clearance profiles of neutral dextran solutions among the dengue patients at any time-point or in comparison to the healthy volunteers. CONCLUSIONS/SIGNIFICANCE: The surface glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma proteins, forms a complex with the underlying endothelial cells to regulate plasma volume within circumscribed limits. It is likely that during dengue infections loss of plasma proteins from this layer alters the permeability characteristics of the complex; physical and/or electrostatic interactions between the dextran molecules and the glycocalyx structure may temporarily restore normal function, rendering the technique unsuitable for assessing permeability in these patients. The implications for resuscitation of patients with dengue shock syndrome (DSS are potentially important. It is possible that continuous low-dose infusions of dextran may help to stabilize the permeability barrier in patients with profound or refractory shock, reducing the need for repeated boluses, limiting the total

  8. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  9. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  10. Search for the presence of occult hepatitis C in patients with treatment-induced viral clearance using an ultrasensitive assay

    Directory of Open Access Journals (Sweden)

    Dzekova-Vidimliski Pavlina

    2016-01-01

    Full Text Available Introduction. Occult hepatitis C is defined by the presence of virus in the peripheral blood mononuclear cells (PBMCs and/or liver cells, in the absence of serum viremia. Objective. To detect the persistence of occult hepatitis C in hemodialysis (HD patients and patients without renal disease (non-renal with treatment-induced clearance of hepatitis C virus (HCV infection, using assays with a very low detection limit of viremia. Methods. A group of 13 HD patients and a group of 43 non-renal patients, with treatment-induced HCV infection clearance were investigated in the study. The HD patients were treated with pegylated interferon alpha (PEG-IFN-α only, while the non-renal patients were treated with a combination therapy of PEGIFN- α and ribavirin. Detection of a possible persistence of HCV RNA in the PBMCs and plasma samples was assessed by an ultrasensitive reverse transcription polymerase chain reaction (RT-PCR assay (2 IU/ml. Results. HCV RNA was not detected in the PBMCs and plasma samples of HD patients and of non-renal patients, when assessed by the ultrasensitive RT-PCR assay. Conclusion. When a sensitive RT-PCR assay was applied, to determine if treatment induced clearance of HCV infection had been successful, occult hepatitis C could not be detected by an ultrasensitive assay, neither in HD nor in non-renal patients.

  11. Prediction of human drug clearance by multiple metabolic pathways: integration of hepatic and intestinal microsomal and cytosolic data.

    Science.gov (United States)

    Cubitt, Helen E; Houston, J Brian; Galetin, Aleksandra

    2011-05-01

    The current study assesses hepatic and intestinal glucuronidation, sulfation, and cytochrome P450 (P450) metabolism of raloxifene, quercetin, salbutamol, and troglitazone using different in vitro systems. The fraction metabolized by conjugation and P450 metabolism was estimated in liver and intestine, and the importance of multiple metabolic pathways on accuracy of clearance prediction was assessed. In vitro intrinsic sulfation clearance (CL(int, SULT)) was determined in human intestinal and hepatic cytosol and compared with hepatic and intestinal microsomal glucuronidation (CL(int, UGT)) and P450 clearance (CL(int, CYP)) expressed per gram of tissue. Hepatic and intestinal cytosolic scaling factors of 80.7 mg/g liver and 18 mg/g intestine were estimated from published data. Scaled CL(int, SULT) ranged between 0.7 and 11.4 ml · min(-1) · g(-1) liver and 0.1 and 3.3 ml · min(-1) · g(-1) intestine (salbutamol and quercetin were the extremes). Salbutamol was the only compound with a high extent of sulfation (51 and 28% of total CL(int) for liver and intestine, respectively) and also significant renal clearance (26-57% of observed plasma clearance). In contrast, the clearance of quercetin was largely accounted for by glucuronidation. Drugs metabolized by multiple pathways (raloxifene and troglitazone) demonstrated improved prediction of intravenous clearance using data from all hepatic pathways (44-86% of observed clearance) compared with predictions based only on the primary pathway (22-36%). The assumption of no intestinal first pass resulted in underprediction of oral clearance for raloxifene, troglitazone, and quercetin (3-22% of observed, respectively). Accounting for the intestinal contribution to oral clearance via estimated intestinal availability improved prediction accuracy for raloxifene and troglitazone (within 2.5-fold of observed). Current findings emphasize the importance of both hepatic and intestinal conjugation for in vitro-in vivo extrapolation

  12. Renal Replacement Therapy: Purifying Efficiency of Automated Peritoneal Dialysis in Diabetic versus Non-Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Nicanor Vega-Diaz

    2015-07-01

    Full Text Available Background: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD, a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF in patients on peritoneal dialysis (PD is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD patients, with end-stage renal disease (ESRD secondary to diabetic nephropathy (DN in comparison to non-diabetic nephropathy (NDN, using different PD solutions in combination. Design: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. Results: The fraction of renal urea clearance (Kt relative to distribution volume (V (or total body water (Kt/V, or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively, and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively. Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0

  13. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  14. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  15. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  16. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  17. Agalsidase benefits renal histology in young patients with Fabry disease.

    Science.gov (United States)

    Tøndel, Camilla; Bostad, Leif; Larsen, Kristin Kampevold; Hirth, Asle; Vikse, Bjørn Egil; Houge, Gunnar; Svarstad, Einar

    2013-01-01

    The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.

  18. 糖化血红蛋白及糖化血清蛋白与糖尿病肾功能衰竭患者的血糖监测%Effect of HbA1c and glycated serum protein for blood glucose monitor in diabetics with renal failure

    Institute of Scientific and Technical Information of China (English)

    王迪; 尹福在; 李慧妍

    2009-01-01

    Glycated hemoglobin Alc (HbAlc) is an important indicator of blood glucose monitor, which reflects the average blood glucose level of 2-3 months before the detection. In the patients with chronic renal failure (CRF), some factors can affect the level of HbA 1 c, such as anemia, acidosis, oxidative stress, in-sulin resistance, hemodialysis and application of erythropoietin (EPO). Glycated serum protein (GSP) re-flects the average blood glucose level of 2-3 weeks before the detection,which is only associated with the plas-ma proteins. It is almost not affected by hemoglobin, EPO treatment and other factors mentioned above and is more sensitive to the changes of blood glucose in a short period. GSP may be more appropriate for glucose mo-nitoring than HbAlc to diabetics with renal failure.%糖化血红蛋白(Hb)A1c是血糖监测的苇要指标,反映检测前2~3个月的平均血糖水平.慢性肾功能衰竭(CRF)患者存在贫血、酸中毒、氧化应激、胰岛素抵抗、血液透析及促红细胞生成素(EPO)的应用等因素,对HbA1c的测定会造成影响.糖化血清蛋白(GSP)反映检测前2~3周的平均血糖水平,仅受血浆蛋白的影响,几乎不受血红蛋白和EPO治疗等以上因素的影响,且对短时间内的血糖变化更为敏感.将GSP作为糖尿病肾功能衰竭患者血糖监测指标可能比HbA1c更理想.

  19. Tip Clearance Flows in Turbine Cascades

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Qiao Weiyang; Sun Dawei

    2008-01-01

    This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades.The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10,0.14 and 0.19.At each exit Mach number,experiments axe performed at the tip clearance heights of 1.0%,1.5%,2.0%,2.5% and 3.0% of the blade height.The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied.The results show that at a given tip clearance height,generally,total pressure loss rises with exit Mach numbers proportionally.At a fixed exit Mach number,the total pressure loss augments nearly proportionally as the tip clearance height increases.The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade.Compared to the effects of the tip clearance height,the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.

  20. Elastic clearance change in axisymmetric shearing process

    Science.gov (United States)

    Yoshida, Yoshinori

    2016-10-01

    An axisymmetric shearing experiment is conducted for a sheet of low carbon steel and stainless steel. Elastic change in the clearance between punch and die is measured. The increase of the clearance in shearing is confirmed and the influence of sheared material's flow stress on the clearance change is shown. Finite element analysis (FEA) of shearing with Gurson-Tvergaard-Needlman model (GTN model) is conducted for shearing of the carbon steels with rigid tools as a numerical experiment. Burr height is predicted in the FEA and the result is compared with the experimental result. In addition, the influence of the clearance on stress state in the material is investigated.

  1. 高糖通过TGF-β1/Smad信号通路介导肾小管上皮细胞1型胶原合成的机制探讨%High glucose stimulate collagen Ⅰ synthesis in renal tubular epithelial cells via activated TGF-β/Smad signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孙辽

    2008-01-01

    目的 探讨高糖对肾小管上皮细胞1型胶原(Collagen Ⅰ)合成影响的分子机制.结果 体外培养的大鼠近端肾小管上皮细胞(NRK52E细胞)分为四组:甘露醇组、高糖组、高糖+TGF-β1中和抗体组、高糖+IsG1对照组.ELISA法检测细胞培养上清中TGF-β1的浓度,细胞免疫化学结果 检测p-Smad2/3核表达水平,RT-PCR和Western blot结果 分别检测Collagen Ⅰ mRNA和蛋白的表达.结果 高糖以时间依赖方式上调Collagen Ⅰ mRNA表达.高糖刺激NRK52E细胞24 h和48 h后内源性TGF-β1合成明显增加,约为甘露醇对照组的3倍.与刺激前和甘露醇组比较,高糖刺激24 h可显著上调NRK52E细胞p-Smad2/3核表达水平(t=4.2,t=3.25,P<0.01).TGF-β1中和抗体能抑制高糖介导的p-Smad2/3核表达及Collagen Ⅰ蛋白的表达(t=3.12,t=3.02,P<0.01).结论 高糖通过TGF-β/Smad信号通路介导肾小管上皮细胞Collagen Ⅰ的合成.%Objective To investigate the molecular mechanisms that high glucose stimulate collagen Ⅰ synthesis in renal tubular epi-thelial cells. Methods Normal rat pwximal tubular epithelial (NRK52E) cells were cultured grown in RPMI-1640 medium and were divid-ed four groups: mannitol group, high glucose group, high glucose + neutralizing TGF-β1 antibody group, high glucose + IgG1 group. TGF-β1 in the supematant of cultured cells were measured by enzyme-linked immunosorbent assay (ELISA). Nuclear expression of p-Smad2/3 were examined by immunocytochemistry. Expression of collagen Ⅰ mRNA was detected by RT-PCR. Expression of collagen Ⅰ pro-tein was detected by Western blot. Results High glucose up-regulated the expression of collagen Ⅰ mRNA by time-dependent manor. Com-pared with mannitol group, high glucose markedly increased the level of TGF-β1 in supernatant of cultured cell after 24h and 48h and upreg-ulated p-Smad2/3 nuclear expression(t =4. 2, t = 3.25, P <0.01). Neutralizing TGF-β1 antibody inhibited high glucose- induced p-Smad2

  2. Residual kidney function after donor nephrectomy. Assessment by {sup 99m}Tc-MAG3-Clearance

    Energy Technology Data Exchange (ETDEWEB)

    Hamscho, N.; Doebert, N.; Menzel, C.; Berner, U.; Zaplatnikov, K.; Gruenwald, F. [Hospital of the J.W.G.-University, Frankfurt am Main (Germany). Dept. of Nuclear Medicine; Wilhelm, A.; Gossmann, J.; Scheuermann, E.H. [Hospital of the J.W.G.-University, Frankfurt am Main (Germany). Dept. of Internal Medicine

    2005-07-01

    Aim: We evaluated the long-term residual renal function after donor nephrectomy using {sup 99m}Tc-mercaptoacetyltriglycin (MAG3)-clearance. Donors, methods: Altogether 49 kidney donors were examined using {sup 99m}Tc-MAG3-clearance after nephrectomy for donation to a relative (m:f=11.38; age 55{+-}27 years). The donors were examined 16{+-}8 years postoperatively (1.5-26 years). 42 donors (86%) showed normal creatinine values, whereas the other seven (14%) exhibited slightly elevated levels. 20 donors were examined pre- and postoperatively and compared intraindividually. The kidney function was compared to the age adapted normal values of healthy persons with two kidneys (67-133% of age related mean). Results: After nephrectomy all donors showed a normal perfusion, good secretion, merely physiological intrarenal transit and a normal elimination from the kidneys. The {sup 99m}Tc-MAG3-clearance was 69{+-}15% of the normal mean value of healthy carriers of two kidneys regardless of the gender. 20 donors with a preoperative examination showed a significantly reduced total renal function from 84{+-}15% of the mean normal value preoperatively to 60{+-}15% postoperatively (p<0.005). 15 donors of this group exhibited a significant functional increase of the residual kidney from 40% initially to 60% after nephrectomy (p=0.003). No correlation was found between the initial {sup 99m}Tc-MAG3-clearance measured prior to nephrectomy and the clearance levels after nephrectomy. Also, no correlation between the preoperative {sup 99m}Tc-MAG3-clearance and the postoperative serum creatinine values could be observed. Althogether, 22% of the donors (11/49) developed arterial hypertension 10{+-}8 years after donation (1-23 years). This corresponds to the normal age prevalence of hypertension in the carriers of two kidneys. Three donors suffered from arterial hypertension prior to the operation. Conclusion: Kidney donors with normal or slightly elevated creatinine values postoperatively

  3. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    Directory of Open Access Journals (Sweden)

    Fady T. Botros

    2012-01-01

    Full Text Available Heme oxygenases (HO-1; HO-2 catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n=7 and hemin-treated rats (n=6 were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115±5 mmHg versus 112±4 mmHg and 331±16 versus 346±10 bpm. However, RBF was significantly higher (9.1±0.8 versus 7.0±0.5 mL/min/g, P<0.05, and renal vascular resistance was significantly lower (13.0±0.9 versus 16.6±1.4 [mmHg/(mL/min/g], P<0.05. Likewise, glomerular filtration rate was significantly elevated (1.4±0.2 versus 1.0±0.1 mL/min/g, P<0.05, and urine flow and sodium excretion were also higher (18.9±3.9 versus 8.2±1.0 μL/min/g, P<0.05 and 1.9±0.6 versus 0.2±0.1 μmol/min/g, P<0.05, resp.. The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models.

  4. 不同检测系统测定血清肾功、血糖、淀粉酶结果对比分析%Comparative Analysis of Serum Renal Function, Blood Glucose and Amylase in Different Detection Systems

    Institute of Scientific and Technical Information of China (English)

    徐新生

    2015-01-01

    Objective To compare the detection results of renal function,blood sugar and amylase based on dif erent systems.Methods 300 serum samples col ected from our Clinical Laboratory were tested by two systems.The levels of renal function,blood sugar and amylase were compared.Results Based on the dif erent detection systems,the levels of renal function,blood sugar and amylase were not dif erent ( 0.05);不同检测系统在肌酐、血糖及淀粉酶测定的精密度无差异;结论两种检测系统对肾功、血糖及淀粉酶测定结果具有可比性,测定的精密度较高,能够满足临床使用要求。

  5. Indications and results of the unilateral /sup 123/I-hippurate-clearance in an ambulant urological-nephrological patients collective

    Energy Technology Data Exchange (ETDEWEB)

    Mariss, P.; Haubold, E.

    1988-02-01

    In 572 nephrological-urological ambulant patients 688 estimations of unilateral renal plasma flow were performed after application of 300 kBq/kg /sup 123/I-hippurate using a large field scintillation camera, external scintillation probe over the right shoulder and a computer system. The indications were patients with hypertension, chronic pyelonephritis, unilateral nephrocirrhosis, exclusion or approval of renal failure, furthermore diverse malformations of the urovesical system, nephrolithiasis and follow-up after urological operations. The unilateral renal clearance by /sup 123/I-hippurate represents an important diagnostic tool in urological-nephrological patients with special diseases in addition to morphological and microbiological methods.

  6. The heme oxygenase system suppresses perirenal visceral adiposity, abates renal inflammation and ameliorates diabetic nephropathy in Zucker diabetic fatty rats.

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    Full Text Available The growing incidence of chronic kidney disease remains a global health problem. Obesity is a major risk factor for type-2 diabetes and renal impairment. Perirenal adiposity, by virtue of its anatomical proximity to the kidneys may cause kidney disease through paracrine mechanisms that include increased production of inflammatory cytokines. Although heme-oxygenase (HO is cytoprotective, its effects on perirenal adiposity and diabetic nephropathy in Zucker-diabetic fatty rats (ZDFs remains largely unclear. Upregulating the HO-system with hemin normalised glycemia, reduced perirenal adiposity and suppressed several pro-inflammatory/oxidative mediators in perirenal fat including macrophage-inflammatory-protein-1α (MIP-1α, endothelin (ET-1, 8-isoprostane, TNF-α, IL-6 and IL-1β. Furthermore, hemin reduced ED1, a marker of pro-inflammatory macrophage-M1-phenotype, but interestingly, enhanced markers associated with anti-inflammatory M2-phenotype such as ED2, CD206 and IL-10, suggesting that hemin selectively modulates macrophage polarization towards the anti-inflammatory M2-phenotype. These effects were accompanied by increased adiponectin, HO-1, HO-activity, atrial-natriuretic peptide (ANP, and its surrogate marker, urinary-cGMP. Furthermore, hemin reduced renal histological lesions and abated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, an important transmembrane protein which forms the scaffolding of the podocyte slit-diaphragm allowing ions to filter but not massive excretion of proteins, hence proteinuria. Correspondingly, hemin increased nephrin expression in ZDFs, reduced markers of renal damage including, albuminuria/proteinuria, but increased creatinine-clearance, suggesting improved renal function. Conversely, the HO-blocker, stannous-mesoporphyrin nullified the hemin effects, aggravating glucose metabolism, and exacerbating renal injury and function. The hemin effects were less

  7. High serum enalaprilat in chronic renal failure

    DEFF Research Database (Denmark)

    Elung-Jensen, T; Heisterberg, J; Kamper, A L

    2001-01-01

    in patients with GFR ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10-42)ml/minute/1.73 m2. The median clearance of enalaprilat was 28 (16......BACKGROUND: Most angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic...

  8. To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt.

    Science.gov (United States)

    Wong, Wai-Tat; Choi, Gordon; Gomersall, Charles D; Lipman, Jeffrey

    2015-10-01

    Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Renal teratogens.

    Science.gov (United States)

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O

    2014-09-01

    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  10. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  11. Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children

    Energy Technology Data Exchange (ETDEWEB)

    Schofer, O. [Department of Pediatrics, Johannes-Gutenberg University, Mainz (Germany); Koenig, G. [Department of Pediatrics, Johannes-Gutenberg University, Mainz (Germany); Bartels, U. [Department of Pediatrics, Johannes-Gutenberg University, Mainz (Germany); Bockisch, A. [Department of Nuclear Medicine, Johannes-Gutenberg University, Mainz (Germany); Piepenburg, R. [Department of Nuclear Medicine, Johannes-Gutenberg University, Mainz (Germany); Beetz, R. [Department of Pediatrics, Johannes-Gutenberg University, Mainz (Germany); Meyer, G. [Department of Nuclear Medicine, Ludwig Maximilians University, Munich (Germany); Hahn, K. [Department of Nuclear Medicine, Ludwig Maximilians University, Munich (Germany)

    1995-11-01

    Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm{sup 2} body surface) in addition to normal oral fluid intake, weight-related dose of {sup 99m}Tc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as ``normal`` with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (> grade I) no single kidney and no difference in split renal function > 20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months. (orig.)

  12. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog.

    OpenAIRE

    Olenick, C L

    1999-01-01

    Congenital renal dysplasia was tentatively diagnosed, based on ultrasound and an intravenous urogram, in a 5-month-old female with polyuria and polydipsia. Creatinine clearance measurement revealed that the renal dysplasia was not the cause of the polyuria. A modified water deprivation test eliminated other differential diagnoses and confirmed psychogenic polydipsia.

  13. Renal function after unilateral nephrectomy for Wilms' tumour : The influence of radiation therapy

    NARCIS (Netherlands)

    deGraaf, SSN; vanGent, H; ReitsmaBierens, WCC; vanLuyk, WHJ; Dolsma, WV; Postma, A

    1996-01-01

    The effect of therapy on renal function after unilateral nephrectomy for Wilms' tumour was studied. In the second year following unilateral nephrectomy, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated simultaneously by measuring I-125-iothalamate clearance and

  14. In situ lactate dehydrogenase activity - a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    2016-01-01

    and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen (BUN) or renal histology. However, there is currently a lack of precise methods to directly assess renal injury state non-invasively. Hyperpolarized 13C-pyruvate magnetic resonance...

  15. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    Science.gov (United States)

    Tanaka, E; Nakamura, K

    1989-08-01

    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not affected. After roxatidine acetate, the pharmacokinetics of AP and TMO were unchanged. The cumulative renal excretion (% dose) and formation clearance of 3-hydroxymethyl-3-nor-antipyrine (NORA) were lowered by cimetidine treatment, but not following the administration of roxatidine acetate. ICG clearance was not changed significantly by either pretreatment. The results of this study show that roxatidine acetate does not impair the metabolism of three model substrates used to assess hepatic drug clearance.

  16. Standardization of a method to calculate absolute renal uptake of {sup 99m} Tc-DMSA in children; Padronizacao do metodo para calculo da captacao renal absoluta do {sup 99m}Tc-DMSA em criancas

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Carla Rachel; Sapienza, Marcelo Tatit; Watanabe, Tomoco; Costa, Paulo Luiz Aguirre; Okamoto, Miriam Roseli Yoshie; Garcez, Alexandre Teles; Buchpiguel, Carlos Alberto [Sao Paulo Univ., SP (Brazil). Hospital das Clinicas. Servico de Medicina Nuclear]. E-mail: crachelo@usp.br; Machado, Beatriz Marcondes; Machado, Marcia Melo Campos [Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital Universitario; Liberato Junior, Waldyr de Paula

    2006-01-15

    Objective:To standardize a method and determine normal values for absolute renal uptake of 99m Tc-DMSA in children with normal creatinine clearance. Materials and methods: Twenty-two children (between 7 months and 10 years of age; mean 4.5 years) without clinical evidence of renal disease were studied using 99m Tc-DMSA scintigraphy. Eighteen had normal renal ultrasonography, micturating urethrocystography, creatinine clearance and visual interpretation of the scintigraphy with 99m Tc-DMSA. Four children were excluded, one with incomplete creatinine clearance and three due to reduction in the creatinine clearance. Absolute renal uptake of 99m Tc-DMSA (DMSA-Abs) was expressed as the fraction of the administered dose retained by each kidney six hours after administration of the radiopharmaceutical. Results: DMSA-Abs was 21.8 +- 3.2% for the right kidney and 23.1 +-3.3% for the left kidney. There was no correlation between renal uptake and the age groups studied, although there was a tendency to an increase in the creatinine clearance with age. Conclusion: Normal values of DMSA-Abs can be used as an additional parameter for the initial diagnostic evaluation and during follow-up of renal diseases, mainly when bilateral impairment of renal function is suspected or in a patient with a single functioning kidney (in which renal differential function is of limited value). (author)

  17. Critical evaluation of mannitol determination and clearance

    NARCIS (Netherlands)

    Dorhout Mees, E.J.; Kampman, J.W.; Verschure, J.C.M.

    1958-01-01

    The mannitol clearance in normal persons was found to be lower than is indicated by most authors. The method of the blood collection appeared to have an unexpected influence on the clearance values obtained. In this manner at least some of the discrepancies can be explained.

  18. 15 CFR 752.15 - Export clearance.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU... COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated...

  19. 19 CFR 122.77 - Clearance certificate.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  20. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  1. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  2. Clinical use of amylase clearance and isoamylase measurements.

    Science.gov (United States)

    Levitt, M D

    1979-07-01

    Isoamylase determinations and measurements of the ratio of the renal clearance of amylase relative to creatinine (CAm/CCr) were employed in an attempt to improve the diagnostic accuracy of the standard amylase measurement. An elevated CAm/CCr reflects defective proximal tubular reabsorption of amylase which occurs in virtually all patients with clear-cut acute pancreatitis. However, other conditions that apparently are associated with acute defective tubular function, such as burns and diabetic acidosis, may cause an elevated ratio. Thus, elevations of CAm/CCr cannot be considered to be specific for acute pancreatitis. Pancreatic isoamylase represents, on the average, about 33% of the normal serum amylase activity, whereas about 66% is salivary-type isoamylase. Isoamylase measurements are useful in determining whether an elevated value for serum amylase activity is of pancreatic origin. However, this measurement is not useful for determining whether patients with normal serum amylase activity have pancreatitis.

  3. Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

    Science.gov (United States)

    Okada, N; Imanishi, M; Yoshioka, K; Konishi, Y; Okumura, M; Tanaka, S; Fujii, S

    1999-11-01

    A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, presistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

  4. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  6. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  7. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  8. Clearance of materials from accelerator facilities

    Directory of Open Access Journals (Sweden)

    Rokni Sayed H.

    2017-01-01

    Full Text Available A new Technical Standard that supports the clearance of materials and equipment (personal property from U.S. Department of Energy (DOE accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1 clearance criteria, 2 process knowledge, and 3 measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex.

  9. Concomitant Administration of High-dose Methotrexate and Low-dose Aspirin Without Any Delay in Methotrexate Clearance in a Patient With Osteosarcoma: A Case Report and Review of the Literature.

    Science.gov (United States)

    Renzi, Samuele; Tsimerman, Ekaterina; Taylor, Tracey; Hopyan, Sevan; Koo, Alicia; Gupta, Abha

    2017-09-08

    Methotrexate (MTX) is a commonly used agent in the treatment of oncology patients whose clearance depends on renal health maintaining glomerular filtration and tubular secretion. Thus concomitant use of other drugs that utilize the same mechanism of clearance are generally avoided as this may contribute to increased MTX-associated toxicity. Herein, we describe the use of low-dose aspirin with high-dose MTX in a patient with osteosarcoma. Concomitant aspirin use did not affect the clearance of high-dose MTX and the patient did not experience any MTX-related toxicity including mucositis or renal impairment.

  10. Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing.

    Science.gov (United States)

    Brandimarti, P; Costa-Júnior, J M; Ferreira, S M; Protzek, A O; Santos, G J; Carneiro, E M; Boschero, A C; Rezende, L F

    2013-11-01

    Insulin clearance plays a major role in glucose homeostasis and insulin sensitivity in physiological and/or pathological conditions, such as obesity-induced type 2 diabetes as well as diet-induced obesity. The aim of the present work was to evaluate cafeteria diet-induced obesity-induced changes in insulin clearance and to explain the mechanisms underlying these possible changes. Female Swiss mice were fed either a standard chow diet (CTL) or a cafeteria diet (CAF) for 8 weeks, after which we performed glucose tolerance tests, insulin tolerance tests, insulin dynamics, and insulin clearance tests. We then isolated pancreatic islets for ex vivo glucose-stimulated insulin secretion as well as liver, gastrocnemius, visceral adipose tissue, and hypothalamus for subsequent protein analysis by western blot and determination of mRNA levels by real-time RT-PCR. The cafeteria diet induced insulin resistance, glucose intolerance, and increased insulin secretion and total insulin content. More importantly, mice that were fed a cafeteria diet demonstrated reduced insulin clearance and decay rate as well as reduced insulin-degrading enzyme (IDE) protein and mRNA levels in liver and skeletal muscle compared with the control animals. Furthermore, the cafeteria diet reduced IDE expression and alternative splicing in the liver and skeletal muscle of mice. In conclusion, a cafeteria diet impairs glucose homeostasis by reducing insulin sensitivity, but it also reduces insulin clearance by reducing IDE expression and alternative splicing in mouse liver; however, whether this mechanism contributes to the glucose intolerance or helps to ameliorate it remains unclear.

  11. The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention.

    Science.gov (United States)

    Henriksen, Ulrik L; Henriksen, Jens H

    2015-01-01

    In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.

  12. MR velocity mapping measurement of renal artery blood flow in patients with impaired kidney function

    DEFF Research Database (Denmark)

    Cortsen, M; Petersen, L.J.; Stahlberg, F

    1996-01-01

    Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography...... by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore, a significant correlation between the distribution of renal function and the percent distribution...

  13. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  14. Glucose-6-phosphatase deficiency.

    Science.gov (United States)

    Froissart, Roseline; Piraud, Monique; Boudjemline, Alix Mollet; Vianey-Saban, Christine; Petit, François; Hubert-Buron, Aurélie; Eberschweiler, Pascale Trioche; Gajdos, Vincent; Labrune, Philippe

    2011-05-20

    Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed

  15. Beta 2-Microglobulin clearance as measured by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Woo, J.; Floyd, M.; Longley, M.A.; Cannon, D.C.

    1980-07-01

    We describe a radioimmunoassay for beta 2-microglobulin (beta 2 mu) in serum and urine. We incubated aliquots of diluted samples at room temperature for 1 h with /sup 125/I-labeled beta 2 mu and a rabbit antiserum monospecific for human beta 2 mu, and separated the phases by the double-antibody technique. The logit-log transformed dose-response curve was linear in the range 2 to 64 ng, equivalent to 0.5 to 16 mg/L of serum and 0.5 to 320 mg/L of urine. Assay sensitivity was 2.4 ng of beta 2 mu. Validation studies included tests of precision, accuracy, antibody specificity, and parallelism of the dose-response curves for standard and unknown. In a study of 25 normal individuals, serum and urine beta 2 mu ranged from 1.1 to 2.3 mg/L and 40 to 360 micrograms/24 h; the clearance of beta 2 mu was 8 to 130 microL/min. In 21 renal allograft recipients tested one to five weeks after transplantation, serum and urine beta 2 mu ranged from 3.9 to 15.6 mg/L and 7.2 to 611 mg/24 h; beta 2 mu clearance was 0.60 to 33.3 mL/min. Values for both serum and urine correlated well with severity of allograft rejection.

  16. Numerical Simulation on the Effect of Tip Clearance Size on Unsteadiness in Tip Clearance Flow

    Institute of Scientific and Technical Information of China (English)

    Juan Du; Feng Lin; Hongwu Zhang; Jingyi Chen

    2008-01-01

    Unsteadiness of tip clearance flow with three different tip clearance sizes is numerically investigated in this paper. NASA Rotor 67 is chosen as the computational model. It is found that among all the simulated cases, the un-steadiness exists when the size of the tip clearance is equal to or larger than design tip clearance size. The relative total pressure coefficient contours indicate that region of influence by tip leakage flow augments with the increase of tip clearance size at a fixed mass flow rate. Root Mean Square contours of static pressure distribution in the rotor tip region are provided to illustrate that for design tip clearance (1.1% tip chord) the strongest fluctuating region is located on pressure side of blade near leading edge, while for the larger tip clearance (2.2% tip chord), it is in the region of the interaction between the shock wave and the tip leakage flow.

  17. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1999-01-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

  18. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1999-01-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

  19. Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.

    Science.gov (United States)

    Walter, Jörg; Mortasawi, Amir; Arnrich, Bert; Albert, Alexander; Frerichs, Inez; Rosendahl, Ulrich; Ennker, Jürgen

    2003-06-17

    Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable predictor, even better than the variable age, former number 1, and SC, previously number 9 in the standard set of EuroSCORE variables. The renal function is an important determinant

  20. Blood pressure relationship to nitric oxide, lipid peroxidation, renal function, and renal blood flow in rats exposed to low lead levels.

    Science.gov (United States)

    Dursun, Nurcan; Arifoglu, Canan; Süer, Cem; Keskinol, Leyla

    2005-05-01

    The results of experiments designed to show that inhibition of nitric oxide production in rats exposed to low lead levels increases vascular resistance, decreases renal blood flow and glomerular function, and enhances oxidative stress. Forty-five adult male Sprague-Dawley rats were divided into four groups. Group A was used as controls and consisted of rats that received no treatment; group B acted as NO-inhibited controls by receiving L-NAME (N(G)-nitro-l-arginine methyl ester) as the NO inhibitor; group C was injected intraperitoneally with 8 mg/kg lead acetate for 2 wk; and group D receiving lead acetate plus L-NAME. Compared to healthy controls, significant elevation of the mean (pbpu) in the controls, 488+/-220 bpu in the L-NAME controls, 1050+/-458 bpu in the lead-treated group, and 878+/-487 bpu in the Pb plus L-NAME group. Low-level lead exposure did not change the urinary flow rate, creatinine clearance, and the creatinine, potassium, phosphorus, glucose, and protein excretion in 24-h urine. In the lead plus NO-inhibited rats, a significant decrease in sodium ion excretion was observed (p<0.01). The NO levels of the lead exposed, L-NAME-treated controls, and L-NAME plus lead-exposed groups are significantly lower compared to untreated controls: p<0.002, p<0.001, and p<0.01, respectively. When compared to untreated controls, the plasma malondialdehyde levels were not significantly different in the lead exposed, lead plus L-NAME, and L-NAME control groups. These results suggest that lead-induced hypertension might be related to a decrease of NO and consequent vasoconstriction, rather than to a decrease of renal blood flow or to decreases in renal sodium.

  1. New IVIVE method for the prediction of total human clearance and relative elimination pathway contributions from in vitro hepatocyte and microsome data.

    Science.gov (United States)

    Riede, Julia; Poller, Birk; Umehara, Ken-ichi; Huwyler, Jörg; Camenisch, Gian

    2016-04-30

    Total human clearance is a key determinant for the pharmacokinetic behavior of drug candidates. Our group recently introduced the Extended Clearance Model (ECM) as an accurate in vitro-in vivo extrapolation (IVIVE) method for the prediction of hepatic clearance. Yet, knowledge about relative elimination pathway contributions is needed in order to predict the total human clearance of drug candidates. In the present work, a training set of 18 drug compounds was used to describe the affiliations between in vitro sinusoidal uptake clearance and the fractional contributions of hepatic (metabolic and biliary) or renal clearance to overall in vivo elimination. By means of these quantitative relationships and using a validation set of 10 diverse drug molecules covering different (sub)classes of the Extended Clearance Concept Classification System (ECCCS), the relative contributions of elimination pathways were calculated and demonstrated to well correlate with human reference data. Likewise, ECM- and pathway-based predictions of total clearances from both data sets demonstrated a strong correlation with the observed clinical values with 26 out of 28 compounds within a three-fold deviation. Hence, total human clearance and relative contributions of elimination pathways were successfully predicted by the presented method using solely hepatocyte and microsome in vitro data.

  2. Use of a Microsoft Excel based add-in program to calculate plasma sinistrin clearance by a two-compartment model analysis in dogs.

    Science.gov (United States)

    Steinbach, Sarah M L; Sturgess, Christopher P; Dunning, Mark D; Neiger, Reto

    2015-06-01

    Assessment of renal function by means of plasma clearance of a suitable marker has become standard procedure for estimation of glomerular filtration rate (GFR). Sinistrin, a polyfructan solely cleared by the kidney, is often used for this purpose. Pharmacokinetic modeling using adequate software is necessary to calculate disappearance rate and half-life of sinistrin. The purpose of this study was to describe the use of a Microsoft excel based add-in program to calculate plasma sinistrin clearance, as well as additional pharmacokinetic parameters such as transfer rates (k), half-life (t1/2) and volume of distribution (Vss) for sinistrin in dogs with varying degrees of renal function.

  3. Airway clearance therapy in cystic fibrosis patients.

    Science.gov (United States)

    Pisi, Giovanna; Chetta, Alfredo

    2009-08-01

    Cystic fibrosis (CF) is the most common life-shortening inherited disease affecting Caucasian people. In CF, the major feature of lung disease is the retention of mucus due to impaired clearance of abnormally viscous airway secretions. Airway clearance techniques (ACTs) may significantly improve mucociliary clearance and gas exchange, thereby being of clinical benefit in reducing pulmonary complications in CF patients. ACTs include conventional chest physiotherapy, active cycle of breathing techniques, autogenic drainage, positive expiratory pressure and high-frequency chest compression. In order to suit the needs of patients, families and care-givers, ACTs need to be individually and continuously adapted.

  4. Polypharmacy and Renal Failure in Nursing Home Residents: Results of the Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes (IMREN) Study.

    Science.gov (United States)

    Dörks, Michael; Herget-Rosenthal, Stefan; Schmiemann, Guido; Hoffmann, Falk

    2016-01-01

    Polypharmacy has become an emerging public health issue in recent years, since use of multiple medications or polypharmacy is beneficial for many conditions, but may also have negative effects like adverse drug reactions. The risk further increases in patients with chronic renal failure, a comorbidity very frequent in nursing home residents. Since more than 50% of all drugs were renally excreted, dose adjustments in patients with renal failure are required. To assess polypharmacy in German nursing homes, in particular in residents with renal failure. Multi-center cross-sectional study in 21 nursing homes in Bremen and Lower Saxony/Germany. Baseline data were analysed using descriptive statistics. Multivariable logistic regression model and 95% confidence intervals were used to study the association of renal failure and polypharmacy. Of all 852 residents, the analysis comprised those 685 with at least one serum creatinine value so that the estimated creatinine clearance could be calculated. Of those, 436 (63.6%) had a severe or moderate renal failure, defined as estimated creatinine clearance Polypharmacy (5-9 drugs) was found in 365 (53.3%) and excessive polypharmacy (≥10 drugs) in 112 (16.4%) residents. Diuretics and psycholeptics were the most commonly used drug classes. Severe renal failure (estimated creatinine clearance polypharmacy (OR: 2.8, 95% CI 1.4-5.7). Both, polypharmacy and renal failure are common in German nursing home residents and an association of both could be found. Further studies are needed to assess the appropriateness of polypharmacy in these patients.

  5. Physiologically-based pharmacokinetic modeling of renally excreted antiretroviral drugs in pregnant women.

    Science.gov (United States)

    De Sousa Mendes, Maïlys; Hirt, Deborah; Urien, Saik; Valade, Elodie; Bouazza, Naïm; Foissac, Frantz; Blanche, Stephane; Treluyer, Jean-Marc; Benaboud, Sihem

    2015-11-01

    Physiological changes during pregnancy can affect drug disposition. Anticipating these changes will help to maximize drug efficacy and safety in pregnant women. Our objective was to determine if physiologically-based pharmacokinetics (PBPK) can accurately predict changes in the disposition of renally excreted antiretroviral drugs during pregnancy. Whole body PBPK models were developed for three renally excreted antiretroviral drugs, tenofovir (TFV), emtricitabine (FTC) and lamivudine (3TC). To assess the impact of pregnancy on PK, time-varying pregnancy-related physiological parameters available within the p-PBPK Simcyp software package were used. Renal clearance during pregnancy followed glomerular filtration changes with or without alterations in secretion. PK profiles were simulated and compared with observed data, i.e. area under the curves (AUC), peak plasma concentrations (Cmax ) and oral clearances (CL/F). PBPK models successfully predicted TFV, FTC and 3TC disposition for non-pregnant and pregnant populations. Both renal secretion and filtration changed during pregnancy. Changes in renal clearance secretion were related to changes in renal plasma flow. The maximum clearance increases were approximately 30% (TFV 33%, FTC 31%, 3TC 29%). Pregnancy PBPK models are useful tools to quantify a priori the drug exposure changes during pregnancy for renally excreted drugs. These models can be applied to evaluate alternative dosing regimens to optimize drug therapy during pregnancy. © 2015 The British Pharmacological Society.

  6. Clinical Study on Treatment of Chronic Renal Failure with Shenshuailing

    Institute of Scientific and Technical Information of China (English)

    鞠建伟; 郭亚玲; 梁延平; 孙世宁; 杨建华; 杨素云

    2001-01-01

    The therapeutic effects of Shenshuailing Kou Fu Ye (SKFY肾衰灵口服液, the Oral Liquid for Renal Failure) and Shenshuailing Guan Chang Ye (SGCY肾衰灵灌肠液, the Enema for Renal Failure) were evaluated in treatment of chronic renal failure, with coateg aldehyde oxystarch as the controls. The changes in the clinical symptoms, serum creatinine, blood urea nitrogen and creatinine clearance rate were observed. The total effective rate in the former was 90.46%, and the latter 60.43%.

  7. Pharmacokinetics of the Long‐Acting Basal Insulin LY2605541 in Subjects With Varying Degrees of Renal Function

    Science.gov (United States)

    Linnebjerg, Helle; Choi, Siak Leng; Lam, Eric Chen Quin; Mace, Kenneth F.; Hodgson, Teri S.; Sinha, Vikram P.

    2016-01-01

    Abstract The pharmacokinetics of LY2605541 (basal insulin peglispro), a novel long‐acting basal insulin analogue, was evaluated in 5 groups of subjects with varying degrees of renal function based on creatinine clearance: normal renal function (>80 mL/min), mild renal impairment (51–80 mL/min), moderate renal impairment (30–50 mL/min), severe renal impairment (renal disease (ESRD) requiring hemodialysis. Serial blood samples for pharmacokinetic analyses were collected up to 12 days following a single 0.33 U/kg subcutaneous dose of LY2605541. The apparent clearance (CL/F) and half‐life across groups were not affected by renal function. Cmax values were lower in subjects with increasing severity of renal impairment; however, the small decrease in Cmax did not affect the overall exposure. Regression analysis showed that LY2605541 clearance is independent of renal function (slope = 0.000863; P = .885). The mean fraction of LY2605541 eliminated by a single hemodialysis session was 13% in subjects with ESRD. LY2605541 was generally well tolerated in healthy subjects and those with renal impairment following a single 0.33 U/kg subcutaneous dose. Given these data, no dose adjustment of LY2605541 based on pharmacokinetics is recommended in renal impairment or in patients undergoing hemodialysis. PMID:27163501

  8. Utility of radioisotopic filtration markers in chronic renal insufficiency: Simultaneous comparison of sup 125 I-iothalamate, sup 169 Yb-DTPA, sup 99m Tc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, R.D.; Steinman, T.I.; Beck, G.J.; Skibinski, C.I.; Royal, H.D.; Lawlor, M.; Hunsicker, L.G. (National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD (USA))

    1990-09-01

    Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-DTPA, 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

  9. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...... repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic...... nerve, however, only the Na(+)/K(+)-ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance. The glial cell swelling associated with K(+) clearance is prevented under conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The Na(+)/K(+)/Cl(-) cotransporter...

  10. Multiphoton imaging of renal regulatory mechanisms.

    Science.gov (United States)

    Peti-Peterdi, János; Toma, Ildikó; Sipos, Arnold; Vargas, Sarah L

    2009-04-01

    Most physiological functions of the kidneys, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis, and blood pressure, are achieved by complex interactions between multiple renal cell types and previously inaccessible structures in many organ parts that have been difficult to study. Multiphoton fluorescence microscopy offers a state-of-the-art imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time, noninvasively, and with submicron resolution. This article reviews innovative multiphoton imaging technologies and their applications that provided the most complex, immediate, and dynamic portrayal of renal function-clearly depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology.

  11. Determination of tooth clearances at trochoidal pump

    OpenAIRE

    Ivanović, Lozica T.; Erić, Milan D.; Stojanović, Blaža Ž.; id_orcid 0000-0003-4790-2856; Ilić, Andreja B.

    2011-01-01

    The paper describes the development of a mathematical model of trochoidal gearing with clearances. Gearing of a trochoidal pump's gear set with an outer gear having one gear tooth more than an inner gear is analyzed. The inner gear tooth profile is described by peritrochoidal equidistance and the outer gear profile by a circular arc. Upon the basic principles of ideal profile generation, a mathematical model of gearing with clearances is developed. Using an analytical model, the calculation o...

  12. Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

    Directory of Open Access Journals (Sweden)

    Clarke Margaret

    2010-09-01

    Full Text Available Abstract Background The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP peritoneal dialysis (PD fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Methods/Design Inclusion criteria are adult PD patients (CAPD or APD aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance® or conventional dialysis solution (Stay.safe® for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. Discussion This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Trial Registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527

  13. The evidence for secretion clearance techniques.

    Science.gov (United States)

    Hess, D R

    2001-11-01

    Many acute and chronic respiratory diseases are associated with increased respiratory secretions in the airways. Narrative reviews and a few systematic reviews of secretion clearance techniques have been published. These reviews raise concerns regarding the lack of evidence to support the various secretion clearance techniques. I conducted a comprehensive MEDLINE search of the following subjects: chest physical therapy, chest physiotherapy, postural drainage, forced expiratory technique, autogenic drainage, high-frequency chest wall compression, flutter device and secretions, positive expiratory pressure and secretions, intrapulmonary percussion, mechanical in-exsufflation and secretions. This was followed by a comprehensive search of cross-references to identify additional studies. The results of this review are reported herein. There are a number of methodological limitations of the literature reporting studies of the use of secretion clearance techniques. Most of the studies were small, most used crossover designs, and few used sham therapy. Many studies were limited to short-term outcomes such as sputum clearance with a single treatment session. Despite the clinical observation that retained secretions are detrimental to respiratory function and despite anecdotal associations between secretion clearance and improvements in respiratory function, there is a dearth of high-level evidence to support any secretion clearance technique.

  14. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Ladefoged, S D; Feldt-Rasmussen, B;

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  15. Renal Cysts

    Science.gov (United States)

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  16. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  17. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  18. Mechanism of increased renal clearnace of amylase/creatinine in acute pancreatitis.

    Science.gov (United States)

    Johnson, S G; Ellis, C J; Levitt, M D

    1976-11-25

    We investigated three possible causes of the increased ratio of amylase/creatinine clearance observed in acute pancreatitis. The presence of rapidly cleared isoamylase was excluded by studies of serum and urine, which demonstrated no anomalous isoamylases. In pancreatitis, the ratios (+/-1 S.E.M.) of both pancreatic isoamylase (9.2+/-0.6 per cent) and salivary isoamylase (8.6+/-1.6 per cent) were significantly (P less than 0.01) elevated over respective control values (2.4+/-0.2 and 1.8+/-0.2 per cent). Increased glomerular permeability to amylase was excluded by the demonstration of normal renal clearance of dextrans. We tested tubular reabsorption of protein by measuring the renal clearance of beta2-microglobulin, which is relatively freely filtered at the glomerulus and then avidly reabsorbed by the normal tubule. During acute pancreatitis the ratio of the renal clearance of beta2-microglobulin to that of creatinine was 1.22+/-0.52 per cent, an 80-fold increase over normal (0.015+/-0.002 per cent), with a rapid return toward normal during convalescence. Presumably, this reversible renal tubular defect also reduces amylase reabsorption and accounts for the elevated renal clearance of amylase/creatinine observed in acute pancreatitis.

  19. Prediction of differential creatinine clearance in chronically obstructed kidneys by non-contrast helical computerized tomography

    Directory of Open Access Journals (Sweden)

    Ng C.F.

    2004-01-01

    Full Text Available PURPOSE: We investigate the use of non-contrast helical computerized tomography (NCHCT in the measurement of differential renal parenchymal volume as a surrogate for differential creatinine clearance (CrCl for unilateral chronically obstructed kidney. MATERIALS AND METHODS: Patients with unilateral chronically obstructed kidneys with normal contralateral kidneys were enrolled. Ultrasonography (USG of the kidneys was first done with the cortical thickness of the site with the most renal substance in the upper pole, mid-kidney, and lower pole of both kidneys were measured, and the mean cortical thickness of each kidney was calculated. NCHCT was subsequently performed for each patient. The CT images were individually reviewed with the area of renal parenchyma measured for each kidney. Then the volume of the slices was summated to give the renal parenchymal volume of both the obstructed and normal kidneys. Finally, a percutaneous nephrostomy (PCN was inserted to the obstructed kidney, and CrCl of both the obstructed kidney (PCN urine and the normal side (voided urine were measured two 2 after the relief of obstruction. RESULTS: From March 1999 to February 2001, thirty patients were enrolled into the study. Ninety percent of them had ureteral calculi. The differential CrCl of the obstructed kidney (%CrCl was defined as the percentage of CrCl of the obstructed kidney as of the total CrCl, measured 2 weeks after relief of obstruction. The differential renal parenchymal volume of the obstructed kidney (%CTvol was the percentage of renal parenchymal volume as of the total parenchymal volume. The differential USG cortical thickness of the obstructed kidney (%USGcort was the percentage of mean cortical thickness as of the total mean cortical thickness. The Pearson's correlation coefficient (r between %CTvol and %CrCl and that between %USGcort and %CrCl were 0.756 and 0.543 respectively. The regression line was %CrCl = (1.00 x %CTvol - 14.27. The %CTvol

  20. [Sensitivity and specificity of blood amylase, amylase and creatinine clearance ratio and urinary amylase/urinary creatinine ratio in the diagnosis of acute pancreatitis].

    Science.gov (United States)

    Ligny, G; Meunier, J C; Hayard, P; Ligny, C; Van Cauter, J

    1987-12-01

    The sensitivity and specificity of amylasemia, the ratios of amylase/creatinine clearance and amylasuria/creatininuria were determined in four groups of patients: a control group (n = 43), patients with acute pancreatitis detected on computed tomography (n = 30, 25 cases of alcoholic pancreatitis), patients with an acute surgical abdomen without pancreatitis (n = 25), and patients with renal failure (n = 20). Sensitivity was defined for the acute pancreatitis group and specificity for the other groups. When amylasemia was greater than 20 UI/dl and the amylasuria/creatininuria ratio greater than 100, sensitivity was 98 per cent. The specificity of these two results in patients with an acute surgical abdomen was 98 per cent. When the ratio amylase/creatinine clearance ratio was greater than 4 sensitivity was 73 per cent and specificity in patients with acute surgical abdomen was 75 per cent. These two values were lower than those of the two preceding tests (p less than 0.01). Sensitivity of the association of an amylasemia greater than 13 UI/dl (m + 2SD) with a clearance ratio greater than 4 was 73 per cent. The amylase/creatinine clearance ratio did not seem to be reliable since its change was delayed with respect to the increase of amylasemia and amylasuria. This ratio has a poor specificity as it increased when the clearance of creatinine decreased in the group with an acute surgical abdomen associated with functional or organic renal failure. In these two groups, the correlation between the amylase/creatinine clearance ratio and creatininemia was significant. This suggested that the clearance of creatinine fell more rapidly than the clearance of amylase as renal failure increased.

  1. THE CHALLENGE OF PD PATIENTS: GLUCOSE AND GLUCOSE DEGRADATION PRODUCTS IN PD SOLUTION

    Directory of Open Access Journals (Sweden)

    Yong-Lim Kim

    2012-06-01

    Full Text Available The main osmotic agent found in the peritoneal dialysis (PD solution is glucose. It has been of a wide use for great crystalloid osmotic power at a low concentration, simple metabolism, and excellent safety. On the other hand, anywhere between 60 to 80% of the glucose in the PD solution is absorbed - a 100 to 300 mg of daily glucose absorption. Once into the systemic circulation, glucose can be a cause for metabolic complications including obesity. Indeed, the diabetiform change observed in the peritoneal membrane in the long-term PD patients is believed attributable to the high-concentration glucose in the PD solution. The glucose absorbed from peritoneal cavity raises the risk of ‘glucose toxicity’, leading to insulin resistance and beta cell failure. Clinical similarity can be found in postprandial hyperglycemia, which is known to be associated with oxidative stress, endothelial dysfunction, NF-κb, and inflammation, affecting myocardial blood flow. Moreover, it is a proven independent risk factor of coronary artery disease in patients with type 2 diabetes, particularly of female gender. Though speculative yet, glucose toxicity might explain a higher mortality of PD patients after the first year compared with those on hemodialysis (more so in female, advanced-age patients with diabetes. Also included in the picture are glucose degradation products (GDPs generated along the course of heat sterilization or storage of the PD solution. They have been shown to induce apoptosis of peritoneal mesothelial cells, renal tubular epithelial cells, and endothelial cells, while spurring production of TGF-β and VEGF and facilitating epithelial mesenchymal transition. GDPs provide a stronger reactivity than glucose in the formation of AGEs, a known cause for microvascular complications and arteriosclerosis. Unfortunately, clinical studies using a low-GDP PD solution have provided mixed results on the residual renal function, peritonitis, peritoneal

  2. Melatonin modulates glucose homeostasis during winter dormancy in a vespertilionid bat, Scotophilus heathi.

    Science.gov (United States)

    Srivastava, Raj Kamal; Krishna, Amitabh

    2010-03-01

    The role for melatonin in glucose homeostasis and insulin resistance is not very clear and has recently been an active area of investigation. The present study investigated the role of melatonin in seasonal accumulation of adipose tissue in Scotophilus heathi, with particular reference to its role in glucose homeostasis and development of insulin resistance. The circulating melatonin levels correlated positively (pinsulin resistance condition which improves after winter when most of the fat has been utilized as a metabolic fuel. The high circulating melatonin levels during the period of maximum body fat at the beginning of winter prepare the bats for winter dormancy by modulating the glucose homeostasis through affecting blood glucose levels, muscle and liver glycogen stores, insulin receptor and glucose transporter 4 (GLUT 4) expression. This is also confirmed by in vivo study in which melatonin injection improves the glucose tolerance, increases muscle insulin receptor and GLUT 4 expression, and enhances glucose clearance from the blood. The results of present study further showed that the effect of melatonin injection on the blood glucose levels is determined by the metabolic state of the bats and may protect from decrease in blood glucose level during extreme starvation, however, melatonin when injected during fed state increases glucose clearance from the blood. In summary, the present study suggested that melatonin interferes with the glucose homeostasis through modulating intracellular glucose transport and may protect bats from hypoglycemia during winter dormancy.

  3. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease

    DEFF Research Database (Denmark)

    Idorn, Thomas; Knop, Filip K; Jørgensen, Morten;

    2013-01-01

    Diabetes is the leading cause of end-stage renal disease (ESRD). Owing to renal clearance, several antidiabetic agents cannot be used in patients with ESRD. The present protocol describes an investigator-initiated trial aiming to test safety and efficacy of treatment with the glucagon-like peptide...

  4. High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

    DEFF Research Database (Denmark)

    Saeed, Aso; Dibona, Gerald F; Marcussen, Niels

    2010-01-01

    The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments...

  5. Factors determining renal impairment in unilateral ureteral colic secondary to calcular disease: a prospective study.

    Science.gov (United States)

    Al-Ani, Ammar; Al-Jalham, Khaled; Ibrahim, Tarek; Majzoub, Ahmad; Al-Rayashi, Maged; Hayati, Ahmed; Mubarak, Walid; Al-Rayahi, Jehan; Khairy, Ahmed T

    2015-07-01

    To evaluate all possible risk factors that can cause impairment of overall renal function in patients with unilateral ureteral calculus and a normal contralateral kidney. This is a prospective study of 90 patients who presented to our institute complaining of renal colic secondary to unilateral ureteral calculus. All patients were evaluated with a thorough history, physical examination, and laboratory and radiological investigations including renal function testing, urine analysis, non-contrast computed topography, and radionucleotide scan. Patients were divided into two groups according to their calculated creatinine clearance using the Modification of Diet in Renal Disease (MDRD) formula. Group I (favorable group) had a creatinine clearance >60 ml/min, while group II (unfavorable group) had a creatinine clearance II included 36 patients (40 %). On univariate analysis, factors that were associated with overall renal function impairment were patients' age, urea-to-creatinine ratio (UCR), use of nonsteroidal anti-inflammatory drugs, stone location, and presence of obstruction. However, using binary logistic regression analysis, only patients' age, UCR, and presence of obstruction sustained statistical significance in association with renal function impairment. The study of factors that help explain the presence of renal impairment in patients with unilateral ureteral calculus is important in the clinical setting. Patients' age, urea-to-creatinine ratio, and degree of obstruction seem to be significantly associated with overall renal function impairment.

  6. 急性缺糖缺氧通过增强胆碱酯酶表达促进肾小管细胞的炎性损伤%Acute oxygen and glucose deprivation promotes inflammatory injury of renal tubular cells by enhancing the expression of cholinesterase

    Institute of Scientific and Technical Information of China (English)

    吴明; 吴乐锋; 李明利; 陆俊福; 赖凯; 徐迹; 刘芬; 冯永文

    2016-01-01

    Objective To investigate the injury mechanism of renal tubular cells induced by acute oxygen and glucose depri-vation. Methods Isolation and culture of rat kidney macrophages and renal epithelial cells,constructing co-cultivating model of lacking Oxygen and sugar(Oxygen and glucose deprivation,OGD),Cells were devided into control group and OGD group,and were given OGD treatment for 1 hour,and then carried out normal culture for up to 24 hours in each group. the expression of TNF al-pha,IL-1 beta,IL-10 in supernatant fluid was detected by ELISA,the viability of renal tubular cells was determined by MTT,the expression of mRNA and protein of acetylcholine esterase (AChE) were determined by RT-qPCR and Western Blot respectively. Results The levels of TNF alpha (pg/ml) in the supernatant fluid in cultivation system were (231.67±36.28) in control group VS (428.67±43.16)(P<0.05) in OGD group,the levels of IL-1β (pg/ml) were (116.67±21.64) in control group VS (219.63±43.86) in OGD group(P<0.05),the levels of IL-10 (pg/ml) were (235.67±39.35) in control group VS (432.67±49.72) in OGD group (P<0. 01). The viability of renal tubular cells was (88.41±18.25) VS (46.98±13.87)(P<0.01);The levels of mRNA and protein of AChE in OGD group were higher than those in control group,they were raised (3.82±0.73) and (2.17±0.46) times respectively (P<0.01). Conclusion Acute oxygen and glucose deprivation enhances the expression of cholinesterase in renal macrophages ,the acute in-jury of renal tubular cells induced by OGD was mediated through inflammatory mediators.%目的:探讨急性缺糖缺氧导致肾小管细胞损伤的机制。方法分离培养大鼠肾内巨噬细胞、肾小管上皮细胞,构建两者共培养(transwell)模型,细胞分成对照组及缺糖缺氧(Oxygen and glucose deprivation,OGD)组,给予缺糖缺氧处理细胞1h后再正常培养24h,ELISA法检测两组上清液TNF-α,IL-1β和IL-10的浓度,噻唑蓝(MTT)检测肾小

  7. Effects of Chinese herbal enema therapy combined basic treatment on BUN,SCr,UA,and IS in chronic renal failure patients

    Institute of Scientific and Technical Information of China (English)

    邹川

    2012-01-01

    Objective To assess the clearance role and safety of Chinese herbal enema therapy (CHET) in clearing enterogenic uremic toxins in chronic renal failure (CRF) patients,thus providing evidence for further optimizing the comprehensive treatment. Methods Using nonrandomized concurrent control

  8. Association of Continuous-Equivalent Urea Clearances with Death Risk in Intermittent Hemodialysis

    Directory of Open Access Journals (Sweden)

    Aarne Vartia

    2016-01-01

    Full Text Available Background. Several reports describe favorable results from frequent hemodialysis, but due to the lack of unequivocal dose measures it is not clear whether the benefits are due to more efficient toxin removal or other factors. Methods. The associations with death risk of six continuous-equivalent urea clearance measures were compared in 57 conventional in-center hemodialysis treatment periods of 51 patients, together 114 patient years. The double pool dose measures were calculated with the Solute-Solver program and separately scaled to urea distribution volume or normalized with body surface area. Results. Mortality associated significantly with equivalent renal urea clearance (EKR scaled to urea distribution volume (V (p=0.033 and with EKR normalized with body surface area (BSA (p=0.044 but not with V-scaled (p=0.059 nor BSA-normalized (p=0.183 standard clearance (stdK. Women had significantly higher normalized protein catabolic rate (nPCR, EKR/V, and stdK/V than men but slightly lower BSA-normalized dose measures and lower mortality. Protein catabolic rate and dialysis dose correlated positively with each other and with survival. Conclusions. The prognostically most valid continuous-equivalent clearance in the present material was EKR/V, calculated from double pool urea generation rate, distribution volume, and time-averaged concentration.

  9. A case of delayed methotrexate clearance following administration of a complementary medication containing chlorophyll.

    Science.gov (United States)

    Brooks, Sally L; Sanders, Julie; Seymour, John F; Mellor, James D

    2014-06-01

    A 54-year-old male with relapsed primary cerebral lymphoma and normal renal function was treated with methotrexate (MTX) 3 g/m(2) monthly by intravenous infusion. Throughout treatment the patient self-administered a complementary medicine (Jason Winter's chlorophyll®), which he was advised to cease during methotrexate treatment due to the potential for unknown interactions. For the first four cycles, chlorophyll was ceased two days prior to commencement of methotrexate and withheld until clearance. These cycles were administered without complication, and the methotrexate level reduced to chlorophyll was not ceased and there were no changes to concomitant medications. A literature search found no documented interactions between methotrexate and chlorophyll and the chemotherapy was administered without a delay in treatment. The methotrexate level three days post-administration was 0.36 µmol/L and did not reduce to chlorophyll 48 h prior to methotrexate administration until clearance. There were no further episodes of delayed methotrexate clearance. No impurities were detected in a sample of Jason Winter's chlorophyll®. It is therefore likely that the patient's delayed methotrexate clearance was due to an interaction with chlorophyll. It is recommended that such chlorophyll containing preparations be avoided in patients treated with methotrexate.

  10. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus

    OpenAIRE

    Bays, Harold

    2013-01-01

    Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety d...

  11. Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man

    DEFF Research Database (Denmark)

    Hvidberg, A; Nielsen, M T; Hilsted, J;

    1994-01-01

    The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially......-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production...... and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes....

  12. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low blood glucose or low blood sugar, occurs when ...

  13. 75 FR 38959 - Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting...

    Science.gov (United States)

    2010-07-07

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 745 RIN 2070-AJ57 Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting Program; Reopening of Comment Period AGENCY: Environmental Protection...

  14. Delivery rate affects uptake of a fluorescent glucose analog in murine metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Narasimhan Rajaram

    Full Text Available We demonstrate an optical strategy using intravital microscopy of dorsal skin flap window chamber models to image glucose uptake and vascular oxygenation in vivo. Glucose uptake was imaged using a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-ylamino]-2-deoxyglucose (2-NBDG. SO2 was imaged using the differential absorption properties of oxygenated [HbO2] and deoxygenated hemoglobin [dHb]. This study was carried out on two sibling murine mammary adenocarcinoma lines, 4T1 and 4T07. 2-NBDG uptake in the 4T1 tumors was lowest when rates of delivery and clearance were lowest, indicating perfusion-limited uptake in poorly oxygenated tumor regions. For increasing rates of delivery that were still lower than the glucose consumption rate (as measured in vitro, both 2-NBDG uptake and the clearance rate from the tumor increased. When the rate of delivery of 2-NBDG exceeded the glucose consumption rate, 2-NBDG uptake decreased with any further increase in rate of delivery, but the clearance rate continued to increase. This inflection point was not observed in the 4T07 tumors due to an absence of low delivery rates close to the glucose consumption rate. In the 4T07 tumors, 2-NBDG uptake increased with increasing rates of delivery at low rates of clearance. Our results demonstrate that 2-NBDG uptake in tumors is influenced by the rates of delivery and clearance of the tracer. The rates of delivery and clearance are, in turn, dependent on vascular oxygenation of the tumors. Knowledge of the kinetics of tracer uptake as well as vascular oxygenation is essential to make an informed assessment of glucose demand of a tumor.

  15. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study.

    Science.gov (United States)

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R

    2013-08-01

    Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0-2h] reductions of 35% and 43%, respectively; P Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.

  16. Correlating the amount of urea, creatinine, and glucose in urine from patients with diabetes mellitus and hypertension with the risk of developing renal lesions by means of Raman spectroscopy and principal component analysis

    Science.gov (United States)

    Bispo, Jeyse Aliana Martins; de Sousa Vieira, Elzo Everton; Silveira, Landulfo; Fernandes, Adriana Barrinha

    2013-08-01

    Patients with diabetes mellitus and hypertension (HT) diseases are predisposed to kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through Raman spectroscopy in order to predict the evolution to complications and kidney failure. Urine samples were collected from control subjects (CTR) and patients with diabetes and HT with no complications (lower risk, LR), high degree of complications (higher risk, HR), and doing blood dialysis (DI). Urine samples were stored frozen (-20°C) before spectral analysis. Raman spectra were obtained using a dispersive spectrometer (830-nm, 300-mW power, and 20-s accumulation). Spectra were then submitted to principal component analysis (PCA) followed by discriminant analysis. The first PCA loading vectors revealed spectral features of urea, creatinine, and glucose. It has been found that the amounts of urea and creatinine decreased as disease evoluted from CTR to LR/HR and DI (PC1, p<0.05), and the amount of glucose increased in the urine of LR/HR compared to CTR (PC3, p<0.05). The discriminating model showed better overall classification rate of 70%. These results could lead to diagnostic information of possible complications and a better disease prognosis.

  17. Renale Osteopathie

    OpenAIRE

    Horn S

    2001-01-01

    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  18. Renale Knochenerkrankungen

    Directory of Open Access Journals (Sweden)

    Mayer G

    2008-01-01

    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  19. Centrifugal compressor tip clearance and impeller flow

    Energy Technology Data Exchange (ETDEWEB)

    Jaatinen-Varri, Ahti; Tiainen, Jonna; Turunen-Saaresti, Teemu; Gronman, Aki; Ameli, Alireza; Backman, Jari [Laboratory of Fluid Dynamics, LUT School of Energy Systems, Lappeenranta University of Technology, Lappeenranta (Finland); Engeda, Abraham [Turbomachinery Laboratory, Dept. of Mechanical Engineering, Michigan State University, East Lansing (United States)

    2016-11-15

    Compressors consume a considerable portion of the electricity used in the industrial sector. Hence, improvements in compressor efficiency lead to energy savings and reduce environmental impacts. The efficiency of an unshrouded centrifugal compressor suffers from leakage flow over the blade tips. The effect of tip leakage flow on the passage flow differs between the full and splitter blade passages. In this study, the differences in the flow fields between the full and splitter blade passages were studied numerically in detail. An industrial high-speed compressor with a design pressure ratio of 1.78 was modelled. Numerical studies were conducted with six different tip clearances and three different diffuser widths. The results show that increasing tip clearance considerably increases the reversed flow into the impeller with an unpinched diffuser. The reversed flow then partly mixes into the flow in the same blade passage it entered the impeller and the rest migrates over the blade, mixing with the tip clearance flow. Furthermore, as the reversed and clearance flow mix into the wake, the wake is weakened. As pinch reduces both the reversed flow and clearance flow, the passage wakes are stronger with pinches. However, the pinch is beneficial as the losses at the impeller outlet decrease.

  20. Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

    Science.gov (United States)

    Gupta, Samir K; Pittenger, Amy L; Swan, Suzanne K; Marbury, Thomas C; Tobillo, Emlyn; Batra, Vijay; Sack, Marshall; Glue, Paul; Jacobs, Sheila; Affrime, Melton

    2002-10-01

    This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.

  1. Assessment of Renal Perfusion in a Canine Model Using FS069, A New Transpulmonary Echocontrast Agent.

    Science.gov (United States)

    Mobarek, Sameh K.; Kates, Marc A.; Murgo, Joseph P.; Moreno, Carlos A.; Revall, Susan; Cheirif, Jorge

    1997-09-01

    We have previously demonstrated the safety and efficacy of FS069, a new transpulmonary echocontrast agent, for myocardial opacification. To our knowledge, no information exists regarding the use of this agent for transcutaneous assessment of renal perfusion. We studied 14 mongrel dogs using intravenously administered FS069. Renal ultrasound imaging was performed with a Hewlett-Packard Sonos 1500 using a 3.5-MHz transducer. Renal blood flow (ReBF) was altered using renal artery occlusion in four dogs and dipyridamole (0.56 mg/kg IV) in ten dogs. Renal perfusion was quantitatively assessed before and after each intervention using background subtracted peak intensity. ReBF was assessed with radiolabeled microspheres in ten dogs. Renal opacification was observed in all 14 dogs at baseline. The intravenous contrast dose required to produce optimal renal opacification ranged from 0.3-0.7 cc. After renal artery occlusion, peak intensity was reduced from 5.4 +/- 5.8 to 0.93 +/- 1.1 units (r = 0.99, P change from baseline). The inverse relation between ReBF and peak intensity observed suggests vasoconstriction of the afferent arterioles in response to dipyridamole and a reduced clearance of the contrast. These findings are in agreement with previous data demonstrating decreased renal thallium clearance postdipyridamole administration. Our data document the feasibility to assess renal perfusion under various flow states after intravenous injection of FS069.

  2. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  3. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  4. Trypsin/creatinine clearance ratio and serum immunoreactive trypsin in digestive and pancreatic diseases.

    Science.gov (United States)

    Del Favero, G; Fabris, C; Bonvicini, P; Piccoli, A; Baccaglini, U; Pedrazzoli, S; Burlina, A; Naccarato, R

    1985-01-01

    The behavior of trypsin/creatinine clearance ratio (Ctr/Ccr) and serum immunoreactive trypsin (IRT) was evaluated in a total of 168 subjects with pancreatic cancer, chronic pancreatitis and non-pancreatic digestive diseases. Amylase/creatinine clearance ratio (Cam/Ccr) and serum amylase levels were also evaluated in order to establish their possible relationship with Ctr/Ccr and IRT values. Elevated Ctr/Ccr and IRT values were observed in several patients with pancreatic cancer and chronic pancreatitis. Abnormal IRT and Ctr/Ccr values were found in 28.2 and 4% of non-pancreatic digestive diseases, respectively. IRT and amylase serum levels showed consensual modifications, while Ctr/Ccr showed a behavior different from that of Cam/Ccr. Liver damage seems to play a role in increasing serum IRT levels of patients without pancreatic involvement, while the increased Ctr/Ccr seems to depend on other factors, for instance renal tubular dysfunction.

  5. Differential effect of T-type voltage-gated calcium channel disruption on renal plasma flow and glomerular filtration rate in vivo

    DEFF Research Database (Denmark)

    Thuesen, Anne D; Andersen, Henrik; Cardel, Majken

    2014-01-01

    of two T-type Cav knock-out mice strains. Continuous recordings of blood pressure and heart rate, and para-aminohippurate clearance (renal plasma flow) and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild type and Cav 3.1-/- and Cav 3.2-/- mice. Contractility of afferent...

  6. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

    Directory of Open Access Journals (Sweden)

    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  7. Uses and limitations of renal scintigraphy in renal transplantation monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Heaf, J.G. [Department of Nephrology, Herlev Hospital, University of Copenhagen (Denmark); Iversen, J. [Department of Clinical Physiology, Herlev Hospital, University of Copenhagen (Denmark)

    2000-07-01

    The value of thrice weekly technetium-99m mercaptoacetyltriglycine renography after renal transplantation was investigated in 213 consecutive transplants. A grading system was used: 0 = normal renogram; 1 = normal uptake, reduced excretion; 2 = normal uptake, flat excretion curve; 3 = rising curve; 4 = reduced rate of uptake, rising curve and reduced absolute uptake; 5 = minimal uptake. The initial renogram grade (RG) was primarily a marker of ischaemic damage, being poorer with cadaver donation, long cold ischaemia (>24 h), and high donor and recipient age. High primary RG predicted primary graft non-function, long time to graft function, low discharge Cr EDTA clearance and low 1- and 5-year graft survival. Discharge RG predicted late (>6 months) graft loss. RG was highly correlated (P<0.001) with creatinine and creatinine clearance, and changes in RG were correlated with changes in renal function. A change in RG of 0.5 was non-specific, while a change of 1 or more predicted clinical complications in 95% of cases. The negative predictive value was low (58%). RG change antedated clinical diagnosis in only 38% of cases, and in only 14% of acute rejections did an RG change of 1 or more antedate a rising creatinine. RG did not contribute to the differential diagnosis between acute rejection, acute tubulointerstitial nephropathy and cyclosporine toxicity. In conclusion, an initial renography after transplantation is valuable as it measures ischaemic damage and predicts duration of graft non-function and both short and long-term graft survival. A review of the literature suggests that the indication for serial scintigraphic monitoring for functioning grafts is less certain: the diagnostic specificity is insufficient for it to be the definitive investigation for common diagnostic problems and it does not give sufficient advance warning of impending problems. (orig.)

  8. O efeito do esteviol, um glicosídeo da Stevia rebaudiana, no clearance da glicose em ratos

    OpenAIRE

    2009-01-01

    Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previ...

  9. Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants.

    Science.gov (United States)

    Schwartz, Janice B

    2016-10-01

    To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft-Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. Simulation and retrospective data analysis. Community, academic institution, nursing home. Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). Age, height, weight, sex, race, serum creatinine, CrCL-CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  10. Clearance of beta-2-microglobulin and middle molecules in haemodiafiltration.

    Science.gov (United States)

    Tattersall, James

    2007-01-01

    Middle molecules, consisting mostly of peptides and small proteins with molecular weight the range of 500-60,000 Da, accumulate in renal failure and contribute to the uraemic toxic state. Beta2-microglobulin (beta2-MG) with a molecular weight of 11,000 is considered representative of these middle molecules. These solutes are not well cleared by low-flux dialysis. High-flux dialysis will clear middle molecules, partly by internal filtration. This convective component of high-flux dialysis can be enhanced in a predictable way by haemodiafiltration (HDF). The convective and diffusive clearance rates of any middle molecule across any haemodiafilter can be predicted from known or measurable factors such as its sieving coefficient, bound fraction and molecular weight. The removal of middle molecules is also influenced by factors within the patient. Beta2-MG is distributed within the extracellular fluid. During HDF, beta2-MG must transfer into the intravascular compartment across the capillary walls. This transcapillary transfer at a rate of approximately 100 ml/min slows beta2-MG removal from the body. Continuing transfer after the end of a treatment session results in a significant rebound of beta2-MG levels. This intercompartment transfer and its effect on beta2-MG clearance and concentration can be predicted by a 2-compartment model. By extrapolation, the behaviour of other middle molecules can be predicted. The 2-compartment model, which takes non-dialytic beta2-MG clearance at a rate of 3 ml/min and beta2-MG generation at a rate of 0.1 mg/min into account, can predict the effect of any HDF schedule on beta2-MG levels. Low-flux dialysis results in a beta2-MG level of around 40 mg/l. Three times weekly, 4-hour HDF can reduce beta2-MG levels to around 20 mg/l. Long (nocturnal) HDF can reduce beta2-MG levels to around 10 mg/l, compared to physiological levels of less than 5 mg/l.

  11. Amylase-creatinine clearance ratio. A simple test to predict gentamicin nephrotoxicity.

    Science.gov (United States)

    Aderka, D; Tene, M; Graff, E; Levo, Y

    1988-05-01

    The initial target of aminoglycoside nephrotoxicity is the proximal tubule. Yet, no simple test is available to predict such toxicity. Taking advantage of the fact that amylase is filtered in the glomerulus and reabsorbed by the proximal tubules, we prospectively examined in 23 patients if changes in renal amylase creatinine clearance ratio (ACCR) can predict gentamicin nephrotoxicity. Eighteen of these patients had an initial creatinine clearance (rCcr) above 30 mL/min. Eleven of them (group A) had an ACCR above 3.5% (control 3% +/- 1.03%) and all exhibited an average reduction of 32.2% +/- 11.6% in rCcr following one week of gentamicin therapy. In contrast, only one of seven patients (group B) with an initial ACCR below 3.5% had a reduction, albeit transient, in rCcr. During gentamicin therapy, group A patients had a further increase in ACCR which was proportional to the reduction observed in rCcr (r = -.54). Our preliminary data suggest that ACCR may prove a simple and possibly a reliable predictor of kidney function deterioration during gentamicin therapy in patients with rCcr above 30 mL/min: patients with pretherapy ACCR above 3.5% may exhibit a deterioration in the creatinine clearance during the first week of therapy. For patients with pretherapy renal failure (rCcr less than 30 mL/min) the creatinine levels (but not the ACCR) seem to retain their significance in predicting and monitoring further renal function deterioration during aminoglycoside therapy.

  12. Unsteady Tip Clearance Flow in an Isolated Axial Compressor Rotor

    Institute of Scientific and Technical Information of China (English)

    Hongwu ZHANG; Xiangyang DENG; Jingyi CHEN; Weiguang HUANG

    2005-01-01

    The paper investigates effects of operating conditions, tip clearance sizes and external unsteady excitations on the unsteady tip clearance flow in an isolated axial compressor rotor by unsteady 3D Navier-Stokes simulations. The results show that the unsteady tip clearance vortex takes a periodic flow behavior in the rotor tip region. With the decrease of the flow coefficient, the unsteady tip clearance vortex is enhanced and its frequency becomes lower. A larger tip clearance size can cause bigger unsteady fluctuation amplitude and a lower fluctuation frequency of the tip clearance vortex at the near stall operating condition. The unsteady excitation with the natural frequency of the tip clearance vortex can enhance the unsteadiness of the tip clearance vortex and improve the overall rotor performance. The frequency of the unsteady tip clearance vortex is independent of external unsteady excitations with different frequencies.

  13. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.

  14. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ozlem Tiryaki

    2013-01-01

    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  15. Forty-five-year follow-up on the renal function after spinal cord injury

    DEFF Research Database (Denmark)

    Elmelund, M; Oturai, P S; Toson, B;

    2016-01-01

    STUDY DESIGN: Retrospective chart review. OBJECTIVES: To investigate the extent of renal deterioration in patients with spinal cord injury (SCI) and to identify risk indicators associated with renal deterioration. SETTING: Clinic for Spinal Cord Injuries, Rigshospitalet, Hornbæk, Denmark. METHODS......: This study included 116 patients admitted to our clinic with a traumatic SCI sustained between 1956 and 1975. Results from renography and (51)Cr-EDTA plasma clearance were collected from medical records from time of injury until 2012, and the occurrence of renal deterioration was analysed by cumulative...... increased the risk of moderate and severe renal deterioration. CONCLUSION: Renal deterioration occurs at any time after injury, suggesting that lifelong follow-up examinations of the renal function are important, especially in patients with dilatation of UUT and/or renal/ureter stones....

  16. Pharmacomechanical thrombolysis for renal salvage after filter migration and renal vein thrombosis.

    Science.gov (United States)

    Kiguchi, Misaki; McDonald, Kerry-Ann; Govindarajan, Siddarth; Makaroun, Michel S; Chaer, Rabih A

    2011-05-01

    A 64-year-old woman underwent prophylactic inferior vena cava filter placement immediately after spinal surgery for pulmonary embolus prophylaxis. One week after surgery, acute renal failure developed, and she required hemodialysis secondary to filter migration with iliocaval and renal vein thrombosis. Pharmacomechanical thrombolysis was performed, with complete recovery of renal function and no evidence of recurrence on follow-up imaging. This report highlights an important and rare complication of filter placement and the importance of prompt thrombus debulking to preserve end organ function while reducing the risks of hemorrhagic complications. Pharmacomechanical thrombolysis allows prompt clearance of venous outflow channels and is attractive in patients with end-organ compromise and high risk for bleeding.

  17. Impact of Gentamicin Coadministration along with High Fructose Feeding on Progression of Renal Failure and Metabolic Syndrome in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zaid O. Ibraheem

    2014-01-01

    Full Text Available The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F received standard rodents chow with free access to drinking water supplemented with 20% (W/V fructose for the same abovementioned period, (FG was fed as group F and was given 80 mg/kg (body weight/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.

  18. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  19. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  20. Insulin-like growth factor I preserves renal function postoperatively.

    Science.gov (United States)

    Franklin, S C; Moulton, M; Sicard, G A; Hammerman, M R; Miller, S B

    1997-02-01

    Deterioration of renal function, which can lead to postoperative renal failure, is a complication of surgery involving the suprarenal aorta and surgery involving the renal arteries. Fifty-four patients who were at risk for developing this complication were enrolled in a double-blind, randomized, placebo-controlled trial of insulin-like growth factor (IGF-I) as a therapeutic agent to prevent the decline in renal function. The primary end point was the incidence of renal dysfunction, defined as a reduction of the glomerular filtration rate (creatinine clearance) at each of three measurements over 72 h. IGF-I (100 microg/kg subcutaneously every 12 h for 6 doses) or placebo was administered on admission to the intensive care unit immediately postoperatively. IGF-I- and placebo-treated groups were well matched for sex, age, type of surgery, renal ischemic time during surgery (ischemic index), baseline creatinine clearance, and baseline serum creatinine. No patient in the study developed acute renal failure postoperatively. IGF-I was well tolerated. A smaller proportion of patients in the IGF-I group had a postoperative decline in renal function (22%) than in the placebo-treated group (33%). There were no significant differences in levels of serum creatinine at time of discharge, length of hospital stay, length of intensive care unit stay, length of intubation, or incidence of dialysis or death. Our findings establish the feasibility and potential utility for the use of IGF-I to reduce the incidence of postoperative renal dysfunction in high-risk patients.

  1. Chronic Renal Failure, Cachexia, and Ghrelin

    Directory of Open Access Journals (Sweden)

    A. Laviano

    2010-01-01

    Full Text Available Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  2. Chronic renal failure, cachexia, and ghrelin.

    Science.gov (United States)

    Laviano, A; Krznaric, Z; Sanchez-Lara, K; Preziosa, I; Cascino, A; Rossi Fanelli, F

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  3. [Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)].

    Science.gov (United States)

    Morabito, S; Guzzo, I; Vitaliano, E; Muzi, L; Solazzo, A; Pistolesi, V; Pierucci, A

    2006-01-01

    In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

  4. Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Bagger, Jonatan I; Knop, Filip K

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have...

  5. Renal effects of canagliflozin in type 2 diabetes mellitus.

    Science.gov (United States)

    Perkovic, Vlado; Jardine, Meg; Vijapurkar, Ujjwala; Meininger, Gary

    2015-12-01

    Chronic kidney disease is commonly associated with type 2 diabetes mellitus (T2DM) and may impact the efficacy and safety of glucose-lowering therapies. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces blood glucose levels in patients with T2DM by lowering the renal threshold for glucose, thereby promoting urinary glucose excretion. This review describes the pharmacology, efficacy and safety of canagliflozin according to kidney function in participants with T2DM. Published articles that reported efficacy, safety and pharmacokinetics/pharmacodynamics data for canagliflozin in patients with T2DM and impaired renal function, and renal safety data with canagliflozin in various populations of patients with T2DM through May 2015 were included. Early transient reductions in estimated glomerular filtration rate were observed with canagliflozin; these changes generally stabilized or attenuated over time and reversed after discontinuation, suggesting no renal (glomerular or tubular) damage with canagliflozin treatment. Urinary albumin-to-creatinine ratios were reduced with canagliflozin. Canagliflozin was generally well tolerated in patients with normal or mild to moderately impaired renal function, with a modestly higher incidence of renal-related adverse events and volume depletion-related adverse events in patients with moderate renal impairment. Adverse events related to potassium elevations were infrequent with canagliflozin 100 mg regardless of kidney function status; however, patients with moderately impaired kidney function experienced hyperkalemia more frequently with canagliflozin 300 mg compared with patients treated with either canagliflozin 100 mg or placebo. Canagliflozin was not associated with increased cardiovascular risk across studies; however, relatively few events among patients with impaired renal function meant that the analysis was not adequately powered to examine this outcome, and results from separate trials are awaited

  6. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  7. Renale Osteopathie

    Directory of Open Access Journals (Sweden)

    Horn S

    2001-01-01

    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  8. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); J.L.D. Wattimena (Josias); T. Rietveld (Trinet); J.N.I. van Miert (Joram); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2016-01-01

    textabstractThe purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January

  9. Renal disease in pregnancy.

    Science.gov (United States)

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  10. Effect of U-74500A, a 21-aminosteroid on renal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Kaur, Hitchintan; Satyanarayana, Padi S V; Chopra, Kanwaljit

    2003-03-01

    Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.

  11. Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

    Science.gov (United States)

    2014-04-24

    ARC Score§ Outcome 1 44 F Surgical complication Intra-abdominal infection 3.375 g every 6 h 202.3 4 15 7 Clinical cure 2 47 M MVC Sepsis 3.375 g...every 6 h 100.7 7 12 9 Clinical cure 3 62 M MVC GNR bacteremia 4.5 g every 6 h 98.0 2 7 4 Clinical cure 4 25 M Intestinal volvulus Intra-abdominal...abscess 3.375 g every 6 h 97.8 2 8 7 Clinical cure 5 20 M MVC Sepsis 4.5 g every 6 h 178.6 6 15 9 Clinical cure 6 57 F Small bowel obstruction Suspected VAP

  12. Understanding renal replacement therapy and dosing of drugs in pediatric patients with kidney disease.

    Science.gov (United States)

    Zuppa, Athena F

    2012-01-01

    Multifaceted factors need to be considered when prescribing renal replacement therapy (RRT) and dosing of drugs in pediatric patients with kidney disease. RRTs in pediatrics such as intermittent hemodialysis, continuous venovenous hemofiltration, continuous venovenous hemodialysis, and continuous venovenous hemodiafiltration affect solute and drug clearance. Drug properties such as molecular weight, molecular charge, volume of distribution, and protein binding affect drug clearance. RRT prescription parameters such as blood flow rate, ultrafiltration rate, membrane size, and pore size can also influence drug clearance. Furthermore, the pediatric patient presents additional concerns because of developmental factors in children that affect both pharmacokinetics of drugs.

  13. 30 CFR 57.7028 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  14. 30 CFR 57.7018 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while...

  15. 30 CFR 56.7018 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or...

  16. 14 CFR 23.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... seven inches (for each airplane with nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically.... Positive clearance for airplanes using leaf spring struts is shown with a deflection corresponding to...

  17. Influence of peritoneal transfer status on fasting blood glucose in non-diabetic nephropathy patients on continuous ambulatory peritoneal dialysis

    Institute of Scientific and Technical Information of China (English)

    YU Xu-fang; ZHOU Yun-fei; FENG Ling; ZHANG Dong-liang; LIU Wen-hu

    2009-01-01

    Background Extra glucose load in peritoneal dialysis is an important cause of newly-occurred diabetic mellitus, which initiates insulin treatment in some of the dialytic patients.The purpose of this study was to discuss the influence of the peritoneal transfer status on fasting blood glucose in non-diabetic nephropathy patients who are on continuous ambulatory peritoneal dialysis (CAPD).Methods One hundred and forty-five patients with total KT/V per week over 2.0 were recruited, including 60 males and 85 females. Fasting blood glucose (FBG), creatinine, blood urea nitrogen (BUN), blood albumin, blood lipid profile and blood C-reactive protein (CRP) were analyzed at the beginning of the peritoneal dialysis and after 12 months. A peritoneal equilibration test (PET) was carried out at the 3rd month of CAPD, and meantime residual renal function, peritoneal solute clearance rate, ultrafiltration volume and urine volume were also evaluated.Results Twenty-one cases were identified as a low transfer group (L), 32 cases as a low average transfer group (LA), 58 cases as a high average transfer group (HA) and 34 cases as a high transfer group (H). At the end of the 12th month, 83 cases had elevated FBG Through stepwise multiple regression analysis we found the FBG level in these patients was positively related to glucose load and CRP, and negatively related to glucose absorption in the peritoneum (D/D_0) and blood albumin (P<0.05). Kaplan-Meier analysis during a 48-month follow-up found the morbidity of hyperglycemia to be 17/34 cases (50.1%) in the high transfer group, 20/58 cases (34.5%) in the high average transfer group, 11/32 cases (34.3%) in the low average transfer group, and 1/21 cases (5.4%) in the low transfer group.Conclusions Patients with high peritoneal transfer capacity might have the highest morbidity from hyperglycemia among patients with these four different peritoneal transfer status. Glucose load, baseline CRP and FBG level before peritoneal dialysis, and

  18. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  19. Renal involvement in dogs with babesiosis

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2001-07-01

    Full Text Available Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium, fractional clearance of sodium (FcNa and potassium (FcK, urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n =10 and 3 groups of babesiosis cases were studied: mild uncomplicated (n =10, severe uncomplicated (n = 11, and complicated (n = 9. All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serumelectrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant

  20. Paid Living-Unrelated Renal Transplantation Abroad: Too Much Unknown

    Directory of Open Access Journals (Sweden)

    Yalçın SOLAK

    2012-05-01

    Full Text Available OBJECTIVE: Despite the unethical characteristic and unfavorable consequences, paid livingunrelated renal transplantation is still considered as an option for end-stage renal disease patients. This study aimed to compare the medical and surgical complications along with allograft functions of PLURT patients with age and gender matched transplant recipients who received a living or deceased donor kidney at our center. MATERIAL and METHODS: End-stage renal disease patients received PLURT (group 1 in a foreign country and age, and gender matched renal transplant recipients that received renal transplantation from living-related donors (LRT patients; group 2 and deceased donors (DDRT patients; group 3 followed between 2003-2010 at our transplantation center were included in the study. RESULTS: There were no significant differences between groups (Group 1&2 and group 1&3 regarding age, sex, urea, creatinine, creatinine clearance, and proteinuria. Data about patients that received renal transplantation from living-related and deceased-donors at our center were sufficient when compared with PLURT patients. PLURT has a negative impact on patients' survival because of surgical and medical problems. CONCLUSION: In the present study, PLURT, LRT and DDRT patients had early and late complications of renal transplantation which were similarly seen in recent studies. The main problem for unfavorable results of PLURT is the commercial aspect of renal transplantation without considering the risks for ESRD patients.

  1. 含缓释淀粉的肠内营养对老年糖脂代谢和肝肾功能的影响%The effect of enterai nutrition containing slow.release starch on glucose and lipid metabolism,hepatic and renal function in aged patients

    Institute of Scientific and Technical Information of China (English)

    李健; 谢南姿; 沈艺; 罗帮镇; 王海峰

    2011-01-01

    Objective: To investigate the effect of the enteral nutrition containing slow-release starch( Fresubin Diabetes) on glucose and lipid metabolism, hepatic and renal function and nutritional status in aged patients. Methods: 136 aged patients were divided into 3 groups according to the feeding ways: the control group( normal oral diet), the study group 1 (additionally given Fresubin Diabetes orally), and the study group 2 ( fed with Fresubin Diabetes through the nasogastric tube). Total calories were around 30 kcal/( kg · d). Variables including fasting blood glucose, postprandial blood glucose, glycated hemoglobin, serum lipids, hepatic and renal function, high-sensitivity C-reactive protein (hs-CRP)and urinary protein series were measured two weeks after nutritional support. Results: Compared with the control group, the study group 2 had a significant lower 2-hour postprandial blood glucose (P =0.047) and the level of glycated hemoglobin was more close to normal range. The level of semm albumin in two study groups was lower, and the levels of serum globulin and hs-CRP were higher than in the control group. Conclusions: Aged patients may benefit from the enteral nutrition containing slow-release starch in glucose and lipid metabolism, hepatic and renal function. It is recommended that the aged patients with reduced normal oral diet due to the illness be supported by the enteral nutrition as FresubinDiabetes.%目的:探讨含缓释淀粉的肠内营养(EN)制剂,对老年病人糖脂代谢、肝肾功能和营养状况的影响,寻找老年病人合理使用EN的效果评估方法和有效的临床检测指标.方法:将136例老年病人根据进食情况分为三组,以正常进食者作为对照(正常饮食组);因疾病导致进食量减少的病人,给予口服瑞代补充营养(加用EN组);因疾病不能进食者,给予瑞代经鼻饲提供EN(单用EN组).所有病人提供的总热量约126.5 kJ(30 kcal)/(kg·d).EN治疗2周后,检测病人空腹和餐后2

  2. Possible removal of topiramate by continuous renal replacement therapy.

    Science.gov (United States)

    Browning, Linda; Parker, Dennis; Liu-DeRyke, Xi; Shah, Aashit; Coplin, William M; Rhoney, Denise H

    2010-01-15

    Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT). We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF. Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

  3. Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

    Directory of Open Access Journals (Sweden)

    Jia-Sheng Wu

    Full Text Available Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A, Radix et Rhizoma Rhei polysaccharides (P, and Radix Scutellaria flavones (F. Our previous studies have shown that a combination of A, P, and F (APF exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB. APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1, and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate

  4. Dynamics modeling and simulation of mechanism with joint clearance

    Institute of Scientific and Technical Information of China (English)

    BAI Zheng-feng; TIAN Hao; ZHAO Yang

    2010-01-01

    The existence of clearance in the joints of mechanisms system is inevitable.The movements of the real mechanism are deftection from the ideal mechanism due to the clearances and the motion accuracv is decreased.The effects of the hinge clearance on the crank and rocker mechanism system are studied.The svstem dynamics equation with clearance is presented.The contact dynamics model is established using the nonlinear equivalent spring-damp model and the friction effect is considered by using Coulomb friction model.Then the models are incorporated into ADAMS,and based on the model,large numbers numeric simulations are made.The regularity of contact forces in clearance are studied in detail.And the effects of clearance size.clearance friction on the mechanism dynamics characteristic are analyzed.The simulation resuhs Can predict the effects of clearance on the mechanism dynamics characteristic preferably.

  5. Distinguishing aggregate formation and aggregate clearance using cell based assays

    NARCIS (Netherlands)

    E. Eenjes, E.; J.M. Dragich; H. Kampinga (Harm); A. Yamamoto, A.

    2016-01-01

    textabstractThe accumulation of ubiquitinated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to diminished aggrega

  6. 19 CFR 122.26 - Entry and clearance.

    Science.gov (United States)

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  7. GLP-1 Levels Predict Mortality in Patients with Critical Illness as Well as End-Stage Renal Disease.

    Science.gov (United States)

    Lebherz, Corinna; Schlieper, Georg; Möllmann, Julia; Kahles, Florian; Schwarz, Marvin; Brünsing, Jan; Dimkovic, Nada; Koch, Alexander; Trautwein, Christian; Flöge, Jürgen; Marx, Nikolaus; Tacke, Frank; Lehrke, Michael

    2017-07-01

    Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which stimulates glucose-dependent insulin secretion from the pancreas and holds immune-regulatory properties. A marked increase of GLP-1 has been found in critically ill patients. This study was performed to elucidate the underlying mechanism and evaluate its prognostic value. GLP-1 plasma levels were determined in 3 different patient cohorts: 1) critically ill patients admitted to our intensive care unit (n = 215); 2) patients with chronic kidney disease on hemodialysis (n = 173); and 3) a control group (no kidney disease, no acute inflammation, n = 105). In vitro experiments were performed to evaluate GLP-1 secretion in response to human serum samples from the above-described cohorts. Critically ill patients presented with 6.35-fold higher GLP-1 plasma level in comparison with the control group. There was a significant correlation of GLP-1 levels with markers for the severity of inflammation, but also kidney function. Patients with end-stage renal disease displayed 4.46-fold higher GLP-1 concentrations in comparison with the control group. In vitro experiments revealed a strong GLP-1-inducing potential of serum from critically ill patients, while serum from hemodialysis patients only modestly increased GLP-1 secretion. GLP-1 levels independently predicted mortality in critically ill patients and patients with end-stage renal disease. Chronic and acute inflammatory processes like sepsis or chronic kidney disease increase circulating GLP-1 levels. This most likely reflects a sum effect of increased GLP-1 secretion and decreased GLP-1 clearance. GLP-1 plasma levels independently predict the outcome of critically ill and end-stage renal disease patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: plasma norepinephrine concentration, hepatic extraction, and renal release

    DEFF Research Database (Denmark)

    Ring-Larsen, H; Hesse, B; Henriksen, Jens Henrik Sahl

    1982-01-01

    Systemic and renal neurovascular reactivity was investigated in eight patients with cirrhosis and in eight control subjects with fatty liver during postural changes. In the supine position, mean renal blood flow averaged 1.51 and 2.97 ml per gm per min in patients and controls, respectively (p less...... 60 degrees head-up tilt, the increase in NE was similar in both groups. In another 10 patients with cirrhosis in recumbency, the splanchnic arterial-hepatic venous extraction of NE averaged 0.43 (p less than 0.01), and the hepatic clearance of NE averaged 315 ml per min which is of the same order...... be responsible for renal vasoconstriction in these patients. However, systemic and renal neurovascular reactivity seems to be maintained even at an advanced stage of the disease....

  9. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

    OpenAIRE

    Boag, F; Weerakoon, J; Ginsburg, J.; Havard, C W; Dandona, P

    1985-01-01

    To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body ...

  10. Renal actinomycosis with concomitant renal vein thrombosis.

    Science.gov (United States)

    Chang, Dong-Suk; Jang, Won Ik; Jung, Ji Yoon; Chung, Sarah; Choi, Dae Eun; Na, Ki-Ryang; Lee, Kang Wook; Shin, Yong-Tai

    2012-02-01

    Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.

  11. Serum gastrin in patients with chronic renal failure.

    Science.gov (United States)

    Taylor, I L; Sells, R A; McConnell, R B; Dockray, G J

    1980-12-01

    The realisation that circulating gastrin is heterogeneous necessitates a reappraisal of gastrin's role in the increased incidence of duodenal ulcer disease that occurs in chronic renal failure. Radioimmunoassays employing region-specific antisera have been used to examine renal and extrarenal factors controlling serum gastrin concentration in patients with chronic renal failure. The present study has shown that basal serum gastrin concentrations measured with a carboxyl-terminal specific antibody were significantly higher in eight patients with chronic renal failure treated by dietary restriction (388+/-196 pM) than in 14 patients with chronic renal failure treated by haemodialysis (28.7+/-4.6 pM). However, basal gastrin concentrations in both groups of patients were significantly higher than in 25 normal subjects (12.3+/-1.8 pM) and showed significant negative correlations with maximal gastric acid secretion (p renal failure patients who were also achlorhydric. Although the peak postprandial increment in big gastrin concentration in 11 chronic renal failure patients (34.0+/-7.5 pM) was significantly greater (p exogenous little gastrin was similar in four chronic failure patients (clearance half time: 8.1+/-0.7 min) and four normal subjects (clearance half time: 6.5+/-1.2 min). These studies suggest that the human kidney is unimportant in the metabolism of little gastrin. As circulating little gastrin is six times more potent than big gastrin in stimulating acid secretion, these studies suggest that the raised gastrin concentrations observed in patients with chronic renal failure have little significance in terms of their increased incidence of duodenal ulcer disease.

  12. Cooked common beans (Phaseolus vulgaris L.) modulate renal genes in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Lomas-Soria, Consuelo; Pérez-Ramírez, Iza F; Caballero-Pérez, Juan; Guevara-Gonzalez, Ramón G; Guevara-Olvera, Lorenzo; Loarca-Piña, Guadalupe; Guzman-Maldonado, Horacio S; Reynoso-Camacho, Rosalía

    2015-07-01

    Food consumption with different bioactive compounds could reduce the risk of diabetic complications. This study was designed to evaluate the effect of cooked common beans on differentially expressed genes in whole kidney homogenates of streptozotocin-induced diabetic rats. After 4weeks of treatment with a cooked bean supplemented (10%) diet, animals fed with Flor de Mayo bean (FMB) exerted the greatest protective effect, since they presented the lowest blood glucose levels, consistent with an increase in blood insulin levels, a decrease in urine albumin and urea levels and an increase in creatinine clearance (P≤.05). Regarding the gene expression of kidneys evaluated using expressed sequence tag, consumption of cooked beans improved the expression of Glu1, Cps1, Ipmk, Cacna1c, Camk1, Pdhb, Ptbp3 and Pim1, which are related to the elimination of ammonium groups, the regulation of inflammatory and oxidative response, as well as cell signaling and apoptosis. In addition, the beneficial effects observed were not related to their polyphenolic and saponin profile, suggesting the activity of other bioactive compounds or the synergistic interaction of these compounds. These results suggest that the consumption of cooked common beans (FMB) might be used as an alternative for the regulation of genes related to renal alterations. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Correlation between characteristics of MSCT to early changes in renal blood perfusion and fasting plasma glucose in patients with diabetes%糖尿病患者早期 MSCT 肾脏血流灌注特点与空腹血糖的相关性分析

    Institute of Scientific and Technical Information of China (English)

    李凯; 龙莉玲; 吴露珍; 刘春斌

    2015-01-01

    Objective To explore the change characteristics of early renal blood infusion in patients with diabetes and its relation-ship with fasting blood sugar by using multi-slice spiral CT (MSCT)perfusion scan.Methods Thirty cases of T2DM patients within five years of disease course that meet clinical diagnostic criteria (poor DN glycemic control group and good DN glycemic control group with 1 5 cases in each group)and 1 5 cases in the control group underwent bilateral renal perfusion scan using 64-detector spiral CT,thus obtaning their cortical perfusion parameters of bilateral kidneys,including blood flow (BF),blood volume (BV),mean transit time (MTT)and capillary permeability surface (PS).At the same time,for each case,fasting glucose,blood urea nitrogen, serum creatinine and blood uric acid value on the third days after and before perfusion were also measured;the glomemlar filtration rate (C-GFR)was estimated.Statistical analysis was performed on all of these obtained values.Results (1).For the poor DN gly-cemic control group,the average BF value,average BV value and average PS value were reduced,average MTT was prolonged sig-nificantly,and compared with normal group,average BF value and average MTT were statistically significant (P 0.05)for both normal control group and DN groups in the third day before and after renal CT perfusion imaging examination.Conclusion BF,BV and MTT of MSCT perfusion scan can reflect the characteris-ticsof early renal blood infusion in patients with diabetes.And changes of fasting blood sugar in patients with diabetes may influence mean BF and mean MTT of kidney.%目的:利用多层螺旋 CT(MSCT)灌注扫描探讨糖尿病(DM)患者早期肾脏血流灌注变化特点,及其与空腹血糖的关系。方法对30例符合临床诊断标准的2型糖尿病(T2DM)病程5年内患者[糖尿病肾病(DN)血糖控制不良组与 DN 血糖控制良好组各15例],以及正常对照组15例,使用64层螺旋 CT 行双侧肾脏灌注扫描,获得

  14. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  15. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  16. Traumatismo renal

    OpenAIRE

    Rocha, Sofia Rosa Moura Gomes da

    2009-01-01

    Introdução: A realização deste trabalho visa a elaboração de uma revisão sistematizada subordinada à temática da traumatologia renal. Objectivos: Os principais objectivos deste trabalho são: apurar a etiologia, definir a classificação, analisar o diagnóstico e expôr o tratamento e as complicações. Desenvolvimento: Os traumatismos são a principal causa de morte antes dos 40 anos. O rim é o órgão do aparelho génito-urinário mais frequentemente atingido. Os traumatismos renais são mais fre...

  17. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R;

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....

  18. Reduction of metformin renal tubular secretion by cimetidine in man.

    OpenAIRE

    Somogyi, A.; Stockley, C; Keal, J; Rolan, P; Bochner, F

    1987-01-01

    To determine whether cimetidine altered the renal handling of metformin, seven subjects took 0.25 g metformin daily with and without cimetidine 0.4 g twice daily. Blood and urine samples were collected and assayed for metformin, cimetidine and creatinine by h.p.l.c. Cimetidine significantly increased the area under the plasma metformin concentration-time curve by an average of 50% and reduced its renal clearance over 24 h by 27% (P less than 0.008). There was no alteration in the total urinar...

  19. Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

    Science.gov (United States)

    Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

    2008-02-01

    The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

  20. Impacts of blood glucose fluctuation on renal pathologic changes and IGF-1, MMP-2 expression%血糖波动对2型糖尿病大鼠肾组织病理改变及IGF-1 、MMP-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    王桂霞; 周冬梅; 李伟

    2014-01-01

    Objective To investigate the impacts of blood glucose fluctuation on renal pathologic changes and IGF-1,MMP-2 expression.Methods Forty five male Sprague-Dawley (SD) rats were divided into two groups according to random number table method:experimental group (DM group,n =35) and normal control group(N group,n =10).Streptozotocin (35 mg/kg) was used to induce diabetes.SD rats were fed with high sugar and high fat diet for 4 weeks,and then were divided into fluctuating blood glucose group(F group,n =17) and continuous high blood glucose group (C group,n =17).The rats in F group were given intraperitoneal injection of insulin and glucose at different time points every day.The same volume of physiological saline was given to rats in C and N group.High sugar and high fat diets were maintained in rats in F and C group,while ordinary diet were given to the rats in N group.12 weeks later,24 hours urine protein,blood urea nitrogen,serum creatinine were determined,HE and PAS staining were used to observe the renal morphology,and electron microscopy was applied to observe the ultrastructural change of kidney.Expression of IGF-1 and MMP-2 were determined by immunohistochemistry.Results Rats of F group suffered more serious blood glucose fluctuation with CV value significantly higher than that in rats of C and N group.No significant difference of HbA1c between rats of F and C group,while both higher than rats of N group.Compared with C group,rats in F group showed higher 24 hours urinary protein,kidney hypertrophy index,glomerulosclerosis index,thicker of glomerular basement membrane,and greater elevation of IGF-1 expression,while less MMP-2 expression(all P<0.05).Conclusions Blood glucose fluctuation may aggravate diabetic kidney damage,the mechanism of which may be related to the upregulation of IGF-1,while downregulation of MMP-2.%目的 观察血糖波动对2型糖尿病大鼠肾组织病理及胰岛素样生长因子(IGF)-1、基质金属蛋白酶(MMP)-2

  1. 49 CFR Appendix F to Part 512 - OMB Clearance

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false OMB Clearance F Appendix F to Part 512 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... 512—OMB Clearance The OMB clearance number for this part 512 is 2127-0025....

  2. 10 CFR 95.17 - Processing facility clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Processing facility clearance. 95.17 Section 95.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance....

  3. 14 CFR 27.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section 27.661 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  4. 50 CFR 14.53 - Detention and refusal of clearance.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Detention and refusal of clearance. 14.53... PLANTS IMPORTATION, EXPORTATION, AND TRANSPORTATION OF WILDLIFE Inspection and Clearance of Wildlife § 14.53 Detention and refusal of clearance. (a) Detention. Any Service officer, or Customs officer...

  5. 23 CFR Appendix B to Part 1327 - OMB Clearance

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false OMB Clearance B Appendix B to Part 1327 Highways NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURES FOR PARTICIPATING..., App. B Appendix B to Part 1327—OMB Clearance The OMB clearance number of this regulation is OMB...

  6. 8 CFR 280.6 - Bond to obtain clearance; form.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 280.6 Section 280.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 280.6 Bond to obtain clearance; form. A bond to obtain clearance of a...

  7. 10 CFR 95.23 - Termination of facility clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Termination of facility clearance. 95.23 Section 95.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.23 Termination of facility clearance....

  8. 32 CFR 644.527 - Recording Statements of Clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Recording Statements of Clearance. 644.527... PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.527 Recording Statements of Clearance. On property disposals for...

  9. 14 CFR 29.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section 29.661 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  10. 46 CFR 56.75-10 - Joint clearance.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  11. 19 CFR 122.157 - Documents required for clearance.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Documents required for clearance. 122.157 Section 122.157 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... clearance. As a condition precedent to clearance, the aircraft commander shall present to Customs: (a)...

  12. 33 CFR 157.455 - Minimum under-keel clearance.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  13. 8 CFR 1280.6 - Bond to obtain clearance; form.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 1280.6... IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 1280.6 Bond to obtain clearance; form. A bond to obtain clearance of a vessel or aircraft under section 231, 237, 239, 243, 251, 253, 254, 255, 256,...

  14. 76 FR 17615 - Highway-Rail Grade Crossing; Safe Clearance

    Science.gov (United States)

    2011-03-30

    ... Parts 177 and 392 RIN 2137-AE69 & 2126-AB04 Highway-Rail Grade Crossing; Safe Clearance AGENCY: Pipeline... that PHMSA and FMCSA extend the comment period for the Highway-Rail Grade Crossing; Safe Clearance... Crossing; Safe Clearance Notice of Proposed Rulemaking, which was published on January 28, 2011 (76 FR...

  15. 14 CFR 375.24 - Entry and clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Entry and clearance. 375.24 Section 375.24 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL... Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  16. 32 CFR 644.521 - Limitations on clearance cost.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section... PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.521 Limitations on clearance cost. The following principles...

  17. 24 CFR 3285.305 - Clearance under homes.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  18. 32 CFR 644.517 - Clearance of Army lands.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL... and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  19. 14 CFR 1260.63 - Customs clearance and visas.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  20. 10 CFR 706.31 - Clearance of conciliators and arbitrators.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Clearance of conciliators and arbitrators. 706.31 Section... RELATIONS Contract Negotiation and Administration § 706.31 Clearance of conciliators and arbitrators. Conciliators and arbitrators who are regularly assigned to DOE cases may be processed for “Q” clearance at...

  1. Guangzhou Customs Guide to Clearance of Import/Export Goods

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Management of the Enterprises Granted for Convenient and Quick Customs Clearance 1.What is the enterprise granted for convenient and quick customs clearance? Customs General Administration and the Ministry of Foreign Trade and Economic Cooperation jointly issued policy measures to facilitate customs clearance in 2001 to further support the development of hightech industries.The enterprise .

  2. Impaired renal function in owl monkeys (Aotus nancymai infected with Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    R. E. Weller

    1992-01-01

    Full Text Available Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months following infection with the Uganda Palo Alto strain of Plasmodium falciparum. Decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. The results were suggestive of glomerulonephropathy and chronic renal disease.

  3. Renal effects of chronic exposure to organic solvents. A clinical controlled trial

    DEFF Research Database (Denmark)

    Krusell, Lars Romer; Nielsen, H K; Bælum, Jesper

    1985-01-01

    Chronic effects of organic solvents on renal function were measured by creatinine clearances and urinary excretion rates of beta 2-microglobulin and albumin. Forty-three male printing trade workers occupationally exposed to different organic solvents for 9-25 years were compared with 43 age....... This investigation did not reveal any adverse renal effects of moderate chronic exposure to organic solvents in a group of active trade workers....

  4. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

    OpenAIRE

    Agmon, Y; Peleg, H; Greenfeld, Z; Rosen, S.; Brezis, M

    1994-01-01

    Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < ...

  5. eGFR is a reliable preoperative renal function parameter in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Takayuki; Kosuge; Tokihiko; Sawada; Yoshimi; Iwasaki; Junji; Kita; Mitsugi; Shimoda; Nobumi; Tagaya; Keiichi; Kubota

    2010-01-01

    AIM: To evaluate the validity of the estimated glomerular filtration rate (eGFR) as a preoperative renal function parameter in patients with gastric cancer. METHODS: A retrospective study was conducted in 147 patients with gastric cancer. Preoperative creatinine clearance (Ccr), eGFR, and preand postoperative serum creatinine (sCr) data were examined. Preoperative Ccr and eGFR were then compared for their reliability in predicting postoperative renal dysfunction. RESULTS: Among 110 patients with normal preo...

  6. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: Update. Consensus SEMICYUC-SENPE: Acute renal failure Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico: Actualización. Consenso SEMICYUC-SENPE: Insuficiencia renal aguda

    Directory of Open Access Journals (Sweden)

    J. López Martínez

    2011-11-01

    Full Text Available Nutritional support in acute renal failure must take into account the patient's catabolism and the treatment of the renal failure. Hypermetabolic failure is common in these patients, requiring continuous renal replacement therapy or daily hemodialysis. In patients with normal catabolism (urea nitrogen below 10 g/day and preserved diuresis, conservative treatment can be attempted. In these patients, relatively hypoproteic nutritional support is essential, using proteins with high biological value and limiting fluid and electrolyte intake according to the patient's individual requirements. Micronutrient intake should be adjusted, the only buffering agent used being bicarbonate. Limitations on fluid, electrolyte and nitrogen intake no longer apply when extrarenal clearance techniques are used but intake of these substances should be modified according to the type of clearance. Depending on their hemofiltration flow, continuous renal replacement systems require high daily nitrogen intake, which can sometimes reach 2.5 g protein/kg. The amount of volume replacement can induce energy overload and therefore the use of glucose-free replacement fluids and glucosefree dialysis or a glucose concentration of 1 g/L, with bicarbonate as a buffer, is recommended. Monitoring of electrolyte levels (especially those of phosphorus, potassium and magnesium and of micronutrients is essential and administration of these substances should be individually-tailored.El soporte nutricional en la insuficiencia renal aguda está condicionado por el catabolismo del paciente y por el tratamiento del fallo renal. En el paciente crítico es frecuente el fracaso hipermetabólico que obliga a técnicas continuas de reemplazo renal o a hemodiálisis diarias. En los enfermos con catabolismo normal (aparición de nitrógeno ureico inferior a 10 g/día y diuresis conservada se puede intentar un tratamiento conservador. En estos casos es preciso realizar un soporte nutricional

  7. Glucose turnover in 48-hour-fasted running rats

    Energy Technology Data Exchange (ETDEWEB)

    Sonne, B.; Mikines, K.J.; Galbo, H.

    1987-03-01

    In fed rats, hyperglycemia develops during exercise. This contrasts with the view based on studies of fasted human and dog that euglycemia is maintained in exercise and glucose production (R/sub a/) controlled by feedback mechanisms. Forty-eight-hour-fasted rats (F) were compared to fed rats (C) and overnight food-restricted (FR) rats. (3-/sup 3/H)- and (U-/sup 14/C)glucose were infused and blood and tissue sampled. During running (21 m/min, 0% grade) R/sub a/ increased most in C and least in F and only in F did R/sub a/ not significantly exceed glucose disappearance. Plasma glucose increased more in C (3.3 mmol/1) than in FR (1.6 mmol/l) and only modestly (0.6 mmol/l) and transiently in F. Resting liver glycogen and exercise glycogenolysis were highest in C and similar in FR and F. Resting muscle glycogen and exercise glycogenolysis were highest in C and lowest in F. During running, lactate production and gluconeogenesis were higher in FR than in F. At least in rats, responses of production and plasma concentration of glucose to exercise depend on size of liver and muscle glycogen stores; glucose production matches increase in clearance better in fasted than in fed states. Probably glucose production is stimulated by feedforward mechanisms and feedback mechanisms are added if plasma glucose decreases.

  8. Pharmacokinetics of netivudine, a potent anti-varicella zoster virus drug, in patients with renal impairment.

    Science.gov (United States)

    Fillastre, J P; Godin, M; Legallicier, B; Chretien, P; Bidault, R; Gillotin, C; Wooton, R; Posner, J; Peck, R W

    1996-05-01

    The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella zoster virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15 +/- 7 mL/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The mean peak plasma concentrations of netivudine, Tmax, and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. Cmax and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. Tmax and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma.

  9. Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment
.

    Science.gov (United States)

    Min, K Chris; Lasseter, Kenneth C; Marbury, Thomas C; Wrishko, Rebecca E; Hanley, William D; Wolford, Dennis G; Udo de Haes, Joanna; Reitmann, Christina; Gutstein, David E

    2017-09-01

    Sugammadex rapidly reverses moderate and deep rocuronium- or vecuronium-induced neuromuscular blockade at doses of 4 mg/kg and 2 mg/kg, respectively. Sugammadex is renally eliminated. This study evaluated the pharmacokinetics of sugammadex in subjects with renal impairment versus those with normal renal function. This open-label, two-part, phase 1 study included adults with moderate (creatinine clearance (CLcr) 30 - cr cr ≥ 80 mL/min). A single intravenous (IV) bolus injection of sugammadex 4 mg/kg was administered into a peripheral vein over 10 seconds directly by straight needle in part 1 (n = 24; 8/group), and via an IV catheter followed by a saline flush in part 2 (n = 18; 6/group). Plasma concentrations of sugammadex were collected after drug administration. Due to dosing issues in part 1, pharmacokinetic parameters were determined for part 2 only. Safety was assessed throughout the study. Pharmacokinetic data were obtained from 18 subjects. Mean sugammadex exposure (AUC0-∞) in subjects with moderate and severe renal impairment was 2.42- and 5.42-times, respectively, that of healthy controls. Clearance decreased and apparent terminal half-life was prolonged with increasing renal dysfunction. Similar Cmax values were observed in subjects with renal impairment and healthy controls. There were no serious adverse events. Sugammadex exposure is increased in subjects with moderate and severe renal insufficiency due to progressively decreased clearance as a function of worsening renal function. Sugammadex 4 mg/kg was well tolerated in subjects with renal impairment, with a safety profile similar to that of healthy subjects. These results indicate that dose adjustment of sugammadex is not required in patients with moderate renal impairment; however, current safety experience is insufficient to support the use of sugammadex in patients with CLcr < 30 mL/min.
.

  10. Recovery and long-term renal excretion of propofol, its glucuronide, and two di-isopropylquinol glucuronides after propofol infusion during surgery.

    NARCIS (Netherlands)

    Bleeker, C.P.; Vree, T.B.; Lagerwerf, A.J.; Willems-Bree, E. van

    2008-01-01

    BACKGROUND: The metabolism of the short-acting anaesthetic agent propofol has been described over the first 24 h. However, the long-term disposition of propofol and its metabolites is unclear. We describe the pharmacokinetics (renal excretion rates and renal clearance) of propofol and its

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  13. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that helps red ...

  14. Your Glucose Meter

    Science.gov (United States)

    ... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco ... Tips for Testing Your Blood Sugar and Caring for Your Meter Glucose meters test and record how much sugar (called glucose) is in your ...

  15. Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy

    NARCIS (Netherlands)

    Clar, Julie; Gri, Blandine; Calderaro, Julien; Birling, Marie-Christine; Herault, Yann; Smit, G. Peter A.; Mithieux, Gilles; Rajas, Fabienne

    2014-01-01

    Renal failure is a major complication that arises with aging in glycogen storage disease type 1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded by G6pc) deficiency leads to the accumulation of glycogen, an effect resulting in marked nephromegaly and

  16. The existence of an insulin-stimulated glucose and non-essential but not essential amino acid substrate interaction in diabetic pigs

    Directory of Open Access Journals (Sweden)

    Wijdenes Jan

    2011-05-01

    Full Text Available Abstract Background The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle. Little information is available on amino acids (AA as alternative energy-source in diabetes. To study the interaction between insulin-stimulated glucose and AA utilization in normal and diabetic subjects, intraportal hyperinsulinaemic euglycaemic euaminoacidaemic clamp studies were performed in normal (n = 8 and streptozotocin (120 mg/kg induced diabetic (n = 7 pigs of ~40-45 kg. Results Diabetic vs normal pigs showed basal hyperglycaemia (19.0 ± 2.0 vs 4.7 ± 0.1 mmol/L, P P P P P P P . Essential AA clearance was largely unchanged (72.9 ± 8.5 vs 63.3 ± 8.5 mL/kg· min, however clearances of threonine (P P Conclusions The ratio of insulin-stimulated glucose versus AA clearance was decreased 5.4-fold in diabetic pigs, which was caused by a 3.6-fold decrease in glucose clearance and a 2.0-fold increase in non-essential AA clearance. In parallel with the Randle concept (glucose - fatty acid cycle, the present data suggest the existence of a glucose and non-essential AA substrate interaction in diabetic pigs whereby reduced insulin-stimulated glucose clearance seems to be partly compensated by an increase in non-essential AA clearance whereas essential AA are preferentially spared from an increase in clearance.

  17. Absolute 24 h quantification of 99Tcm-DMSA uptake in patients with severely reduced kidney function: a comparison with 51Cr-EDTA clearance.

    Science.gov (United States)

    van de Wiele, C; van den Eeckhaut, A; Verweire, W; van Haelst, J P; Versijpt, J; Dierckx, R A

    1999-09-01

    The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.

  18. ADSORBENTS USED IN THE CLEARANCE OF ENDOTOXIN

    Institute of Scientific and Technical Information of China (English)

    YU Mei; LIU Tao; Hou Guanghui; YUAN Zhi

    2003-01-01

    A series of modified poly (methyl methacrylate, PMMA) resins were prepared and compared their adsorption abilities to endotoxin. The results showed that adsorbents, which were grafted with tertiary amine and long spacing arms, had the best adsorption capacities and good blood compatibility, It is hopeful to be used as adsorbent in hemoperfusion for clinical clearance of endotoxin. The influence of original concentration of endotoxin on adsorption and the adsorption mechanism were also investigated.

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has too little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: ...

  20. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.

    Science.gov (United States)

    Ahad, Amjid; Ahsan, Haseeb; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2015-10-05

    Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.