WorldWideScience

Sample records for renal urate excretion

  1. Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia.

    Science.gov (United States)

    Yang, Hua; Gao, Lihui; Niu, Yanfen; Zhou, Yuanfang; Lin, Hua; Jiang, Jing; Kong, Xiangfu; Liu, Xu; Li, Ling

    2015-01-01

    Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose- and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.

  2. Inhibition of urate excretion by pyrazinoate: a micropuncture study.

    Science.gov (United States)

    Roch-Ramel, F; Weiner, I M

    1975-12-01

    Anesthetized monkeys (Cebus albifrons) undergoing moderate mannitol diuresis were treated with infusions containing lithium urate to elevate the urate concentration in plasma to 45-68 mug/ml and containing the uricosuric drug, 2-nitroprobenecid, to enhance the renal clearance or urate. The urate/inulin clearance ratio was 0.55 +/- 0.03. When pyrazinoate was added to the infusion the clearance ratio fell to 0.26 +/- 0.02. Analysis of free-flow micropuncture samples revealed a major effect of pyrazinoate in the proximal tubule, although an additional, smaller action in the distal tubule could not be definitely excluded. When droplets containing [14C]urate and [3H]inulin were streaked on the surface of the left kidney more urate than inulin appeared in the urine from that kidney (but not the other) within the first 3 min after application. This "excess" excretion of urate could be largely eliminated by pretreatment with pyrazinoate. The results suggest that pyrazinoate inhibits secretion of urate in the proximal tubule.

  3. Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2

    Science.gov (United States)

    Matsuo, Hirotaka; Tsunoda, Tomoyuki; Ooyama, Keiko; Sakiyama, Masayuki; Sogo, Tsuyoshi; Takada, Tappei; Nakashima, Akio; Nakayama, Akiyoshi; Kawaguchi, Makoto; Higashino, Toshihide; Wakai, Kenji; Ooyama, Hiroshi; Hokari, Ryota; Suzuki, Hiroshi; Ichida, Kimiyoshi; Inui, Ayano; Fujimori, Shin; Shinomiya, Nariyoshi

    2016-01-01

    To clarify the physiological and pathophysiological roles of intestinal urate excretion via ABCG2 in humans, we genotyped ABCG2 dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (P = 1.1 × 10−4), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion via ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (P = 6.3 × 10−3) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine. PMID:27571712

  4. Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury.

    Science.gov (United States)

    Hosoyamada, Makoto; Tsurumi, Yu; Hirano, Hidenori; Tomioka, Naoko H; Sekine, Yuko; Morisaki, Takayuki; Uchida, Shunya

    2016-12-01

    Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI). Mice were given a variable content of allopurinol for one week followed by HPLC measurement of urate and creatinine concentrations in spot urine and blood from the tail. The urinary excretion of urate in Urat1-Uox-DKO mice was approximately 25 times higher than those of humans. With allopurinol, the plasma urate levels of Urat1-Uox-DKO mice were lower than those of Uox-KO mice. There were no differences in the urinary urate excretions between Urat1-Uox-DKO and Uox-KO mice administered with 9 mg allopurinol /100 g feed. In the absence of allopurinol, plasma creatinine levels of some Urat1-Uox-DKO mice were higher than those of Uox-KO mice. Consequently, hypouricemia and normouricosuria may indicate that the Urat1-Uox-DKO mouse administered with allopurinol may represent a suitable animal model of RHUC type 1. Urat1-Uox-DKO mice without allopurinol exhibited acute kidney injury, thus providing additional benefit as a potential animal model for EIAKI. Finally, our data indicate that allopurinol appears to provide prophylactic effects for EIAKI.

  5. Effect of hypouricaemic and hyperuricaemic drugs on the renal urate efflux transporter, multidrug resistance protein 4.

    NARCIS (Netherlands)

    El-Sheikh, A.A.K.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Russel, F.G.M.

    2008-01-01

    BACKGROUND AND PURPOSE: The xanthine oxidase inhibitors allopurinol and oxypurinol are used to treat hyperuricaemia, whereas loop and thiazide diuretics can cause iatrogenic hyperuricaemia. Some uricosuric drugs and salicylate have a bimodal action on urate renal excretion. The mechanisms of action

  6. How does whisky lower serum urate level?

    Science.gov (United States)

    Lu, Yang; Nakanishi, Takeo; Fukazawa, Miki; Tamai, Ikumi

    2014-05-01

    Clinical studies have shown that moderate whisky consumption increased renal excretion of urate into urine and decreased serum urate level, but the mechanism involved has not been established. Because renal reabsorption influences serum urate level, the effects of the whisky congeners on urate transporters, urate transporter 1 (URAT1), and voltage-driven urate transporter (URATv1) involved in reabsorptive transport of urate were examined. In transporter-expressing Xenopus oocytes, 12-year-old and 18-year-old whisky congeners inhibited urate uptake by URAT1 with IC50 values of 0.08 ± 0.01 and 0.04 ± 0.01 mg/mL, respectively, while urate uptake by URATv1 was inhibited only at 1 mg/mL. Decreased serum urate level after whisky consumption may be mainly due to inhibition of URAT1 by the congeners.

  7. Non-urate transporter 1-related renal hypouricemia and acute renal failure in an Israeli-Arab family.

    Science.gov (United States)

    Bahat, Hilla; Dinour, Dganit; Ganon, Liat; Feldman, Leonid; Holtzman, Eli J; Goldman, Michael

    2009-05-01

    Idiopathic renal hypouricemia (IRHU) is a rare hereditary disease, predisposing the individual to exercise-induced acute renal failure (EIARF) and nephrolithiasis, and it is characterized by increased clearance of renal uric acid. Most of the described patients are Japanese, who have loss-of-function mutations in the SLC22A12 gene coding for the human urate transporter 1 (URAT1) gene. An 18-year-old youth, who was admitted for EIARF due to IRHU, and six consanguineous Israeli-Arab family members were included in the study. The family members were tested for fractional excretion of uric acid and molecular analysis of the URAT1 gene. Four family members, including the proband, had very low levels of blood uric acid and high rate of fractional excretion (FE urate> 100%) of uric acid. Genetic analysis of the affected family members did not reveal a mutation in the coding regions and intron-exon boundaries of SCL22A12. Haplotype analysis excluded SCL22A12 involvement in the pathogenesis, suggesting a different gene as a cause of the disease. We herein describe the first Israeli-Arab family with IRHU. A non-URAT1 genetic defect that causes decreased reabsorption or, more probably, increased secretion of uric acid, induces IRHU. Further studies are required in order to elucidate the genetic defect.

  8. Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

    Science.gov (United States)

    Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

    2017-01-17

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10(-6)) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10(-7). We observed a strong association (p < 8 × 10(-8)) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10(-6), MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

  9. Renal energy excretion of horses depends on renal hippuric acid and nitrogen excretion.

    Science.gov (United States)

    Hipp, B; Südekum, K-H; Zeyner, A; Goren, G; Kienzle, E

    2017-06-13

    The prediction of renal energy excretion is crucial in a metabolizable energy system for horses. Phenolic acids from forage cell walls may affect renal energy losses by increasing hippuric acid excretion. Therefore, the relationships were investigated between renal energy, nitrogen (N) and hippuric acid excretion of four adult ponies (230-384 kg body weight (BW)) consuming diets based on fresh grass, grass silage, grass cobs (heat-dried, finely chopped, pressed grass), alfalfa hay, straw, extruded straw and soybean meal. Feed intake was measured; urine and faeces were quantitatively collected for three days. Feed was analysed for crude nutrients, gross energy, amino acids and neutral-detergent-insoluble crude protein (CP); faeces were analysed for crude nutrients and cross energy; urine was analysed for N, hippuric acid, creatinine and gross energy. Renal energy excretion (y; kJ/kg BW(0.75) ) correlated with renal N excretion (x1 ; g/kg BW(0.75) ) and renal hippuric acid excretion (x2 ; g/kg BW(0.75) ): y = 14.4 + 30.2x1 +20.7x2 (r = .95; n = 30; p energy losses per gram CP intake: (i) protein supplements (e.g., soybean meal): 4.2-4.9 kJ/g CP intake (ii) alfalfa hay, grains, dried sugar beet pulp: 6.4 kJ/g CP intake, (iii) hay, preserved grass products, straw: 5.2-12.3 kJ/g CP intake (mean 8) and (iv) fresh grass. For group (iii) a negative relationship was observed between renal energy losses per gram of CP and the content of CP or neutral-detergent-insoluble CP in dry matter. © 2017 Blackwell Verlag GmbH.

  10. Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion)

    Science.gov (United States)

    Pang, Minxia; Fang, Yingying; Chen, Suhong; Zhu, Xuexin; Shan, Chaowen; Su, Jie; Yu, Jingjing; Li, Bo; Yang, Yao; Chen, Bo; Liang, Kailun; Hu, Huiming; Lv, Guiyuan

    2017-01-01

    Background The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. Material/Methods Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. Results Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. Conclusions GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters. PMID:28258276

  11. Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

    Science.gov (United States)

    Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2017-03-01

    Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment.

  12. Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

    Science.gov (United States)

    Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo

    2006-02-01

    The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of

  13. Oxidative stress by monosodium urate crystals promotes renal cell apoptosis through mitochondrial caspase-dependent pathway in human embryonic kidney 293 cells: mechanism for urate-induced nephropathy.

    Science.gov (United States)

    Choe, Jung-Yoon; Park, Ki-Yeun; Kim, Seong-Kyu

    2015-01-01

    The aim of this study is to clarify the effect of oxidative stress on monosodium urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS, cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-18, TNF receptor-associated factor-6 (TRAF-6), and mitogen-activated protein kinases were performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by MSU crystals. Fluorescence-activated cell sorting was performed using annexin V for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL-1β siRNA was used for blocking IL-1β expression. MSU crystals promoted ROS, iNOS, and COX-2 expression and also increased TRAF-6 and IL-1β expression in HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase-dependent renal cell apoptosis was induced through attenuation of Bcl-2 and enhanced caspase-3 and caspase-9 expression by MSU crystals, which was significantly reversed by ascorbic acid and transfection of IL-1β siRNA to HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal-regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals. ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also suppressed by transfection with IL-1β siRNA. Oxidative stress generated by MSU crystals promotes renal apoptosis through the mitochondrial caspase-dependent apoptosis pathway.

  14. RENAL CLEARANCE AND URINARY EXCRETION OF CIPROFLOXACIN IN GOATS

    Directory of Open Access Journals (Sweden)

    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.

  15. Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.

    Science.gov (United States)

    Reynolds, Richard J; Vazquez, Ana I; Srinivasasainagendra, Vinodh; Klimentidis, Yann C; Bridges, S Louis; Allison, David B; Singh, Jasvinder A

    2016-02-01

    We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.

  16. Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index

    Science.gov (United States)

    Reynolds, Richard J.; Vazquez, Ana I.; Srinivasasainagendra, Vinodh; Klimentidis, Yann C.; Bridges, S. Louis; Allison, David B.; Singh, Jasvinder A.

    2015-01-01

    Introduction/objectives We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk for incident gout. Method We measured the incidence of gout and associated comorbidities using the Original and Offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the 8 SNPs. Results Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score (GRS) interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P=6.12E-03). Conclusions We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk for gout may involve complex interplay between genes and environment. PMID:26427508

  17. Rotavirus gastroenteritis-associated urinary ammonium acid urate crystals.

    Science.gov (United States)

    Yokoyama, Tadafumi; Sugimoto, Naotoshi; Kato, Eiji; Ohta, Kazuhide; Ishikawa, Sayaka; Ueno, Kazuyuki; Shimizu, Masaki; Yachie, Akihiro

    2015-01-01

    Although ammonium acid urate (AAU) calculi are extremely rare renal stone components, it was recently found that many urinary tract calculi that cause post-renal renal failure in rotavirus (RV) gastroenteritis are AAU calculi. The mechanism of AAU calculi development in RV gastroenteritis has not been fully elucidated. We analyzed data from eight RV gastroenteritis patients who transiently had AAU crystals in their urinary sediment. In these patients, formation of AAU crystals occurred earlier than the formation of AAU calculi. No difference was observed in serum and urine uric acid levels between RV gastroenteritis patients with or without AAU crystals. Interestingly, fractional excretion of sodium was extremely low among patients with AAU crystals. These results suggest that the formation of AAU crystals might not be due to excretion of uric acid, but excretion of sodium.

  18. Expression and clinical significance of URAT1 in renal tissue of patients with uric acid nephrolithiasis%URAT1基因在尿酸结石患者肾脏的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    姚基伟; 李前伟; 付卫华; 郑霁; 鄢俊安; 李为兵

    2015-01-01

    目的:探讨尿酸结石患者尿酸代谢特征以及肾脏URAT1表达改变的意义。方法回顾性分析2012年1月至2013年10月我院收治的24例结石患者的临床资料,按结石成分分为尿酸结石患者9例( A组)、非尿酸性结石患者15例( B组),另选取7例因其他疾病操作而取材做mRNA测定的患者为C组,10例健康体检者为D组(仅用作收集其血尿酸检验结果以及24 h尿液标本)。采集各组参与者一般临床资料以及血液、24 h尿液的尿酸代谢相关指标结果,并应用Real-time PCR技术检测其肾脏URAT1表达情况,所得数据进行组间统计分析比较。结果 A 组患者血尿酸水平、体重指数、年龄显著高于 B 组及 C 组(P0.05)。 Real-time PCR实验结果提示尿酸结石患者肾脏URAT1表达较其他组显著增高(P0. 05). The result of Real-time PCR suggested that the URAT1 renal expression was significantly higher in patients with uric acid nephrolithiasis than other two groups (P<0. 05). Conculusion Patients with uric acid nephrolithiasis are closely related with hyperuricemia,but unrelated with renal over-ex-cretion of uric acid. The upregulated URAT1 expression in the kidney may be an important molecular mechanism of the clinical features.

  19. Infarction of renal transplant with extrarenal excretion of Tc-99m MAG{sub 3} demonstrated by renal scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seok Tae; Kim, Min Woo; Sohn, Myung Hee [Chonbok National University Medical School, Chonju (Korea, Republic of)

    2003-06-01

    A 38-year-old woman with end stage renal disease received a living related donor-renal transplant to the right iliac fossa. She developed anuria a week later. Tc-99m MAG{sub 3} renal scintigraphy demonstrated no perfusion, uptake, or excretion of the radioactive tracer from the renal transplant. The expected area of the renal allograft appeared as a photopenic area with increased rim activity. The gallbladder and bowel activities were observed on delayed images at 24 hours. There was no blood flow within the renal artery on renal doppler examination. This case shows total absence of perfusion and function in the infarcted renal transplant with extrarenal excretion of Tc-99m MAG{sub 3} caused by acute renal artery thrombosis.

  20. Determinants of renal potassium excretion in critically ill patients : The role of insulin therapy

    NARCIS (Netherlands)

    Hoekstra, Miriam; Yeh, Lu; Lansink, Annemieke Oude; Vogelzang, Mathijs; Stegeman, Coen A.; Rodgers, Michael G. G.; van der Horst, Iwan C. C.; Wietasch, Gotz; Zijlstra, Felix; Nijsten, Maarten W. N.

    2012-01-01

    Objectives: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were

  1. Determinants of renal potassium excretion in critically ill patients : The role of insulin therapy

    NARCIS (Netherlands)

    Hoekstra, Miriam; Yeh, Lu; Oude Lansink, Annemieke; Vogelzang, Mathijs; Stegeman, Coen A.; Rodgers, Michael G. G.; van der Horst, Iwan C. C.; Wietasch, Gotz; Zijlstra, Felix; Nijsten, Maarten W. N.

    Objectives: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were

  2. Effects of chronic lithium administration on renal acid excretion in humans and rats

    OpenAIRE

    Weiner, I. David; Leader, John P.; Bedford, Jennifer J.; Verlander, Jill W.; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J.

    2014-01-01

    Abstract Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted signific...

  3. Selective renal vasoconstriction, exaggerated natriuresis and excretion rates of exosomic proteins in essential hypertension

    DEFF Research Database (Denmark)

    Damkjaer, M.; Jensen, Pia Hønnerup; Schwämmle, Veit

    2014-01-01

    AimIn essential hypertension (EH), the regulation of renal sodium excretion is aberrant. We hypothesized that in mild EH, (i) abnormal dynamics of plasma renin concentration (PRC) and atrial natriuretic peptide (ANP) are responsible for the exaggerated natriuresis, and (ii) exosomic protein......). Excretion rates of exosome-related urinary proteins including apical membrane transporters were determined by proteomics-based methods. ResultsIn patients, baseline renal vascular conductance was reduced (-44%, P...

  4. Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion.

    Science.gov (United States)

    Weiner, I David; Mitch, William E; Sands, Jeff M

    2015-08-07

    Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance.

  5. Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

    Directory of Open Access Journals (Sweden)

    T.T. Rosa

    1995-03-01

    Full Text Available The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v -63% and excretion ofsodium (-57% v-79% were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51% than in controls (-39%. Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerularfiltration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

  6. Clinical and functional characterization of URAT1 variants.

    Directory of Open Access Journals (Sweden)

    Velibor Tasic

    Full Text Available Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.

  7. Effects of chronic lithium administration on renal acid excretion in humans and rats.

    Science.gov (United States)

    Weiner, I David; Leader, John P; Bedford, Jennifer J; Verlander, Jill W; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J

    2014-12-01

    Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid-base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long-term lithium therapy with six healthy individuals. Under basal conditions, lithium-treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium-treated and control humans. There were no significant differences between lithium-treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium-treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium-treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg.

  8. Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition

    DEFF Research Database (Denmark)

    Therwani, Safa Al; Rosenbæk, Jeppe Bakkestrøm; Mose, Frank Holden

    2017-01-01

    during 60 min. We measured urine output (UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma vasopressin (p-AVP) and central blood pressure (cBP). RESULTS: During baseline, FENa was unchanged...... in renal water and sodium excretion during NO-inhibition. Most likely, the lack of decrease in AQP2 excretion by tolvaptan could be attributed to a counteracting effect of the high level of p-AVP....

  9. Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Anabel Brandoni

    2017-01-01

    Full Text Available Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2 after 1 (BUO-1, 2 (BUO-2, and 7 (BUO-7 days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.

  10. RENAL ENDOGENOUS ET-1 AND URINARY SODIUM EXCRETION AND MICROALBUMINURIA IN HUMAN SALT-SENSITIVE HYPERTENSION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the urinary endothelin-1 (ET-1) excretion and urinary sodium excretion,microalbuminuria and ambulatory blood pressure(ABP) in salt-sensitive(SS) hypertension patients. Methods Twenty-one cases of normotensive subjects and 32 cases of uncomplicated hypertensive patients were recruited in this study. Salt sensitivity was determined by acute venous saline loading test. Before saline loading, 24-hour ABP measurements were performed. Urine samples were collected to assay ET-1 ,urinary sodium excretion and urinary albumin excretion(UAF). Results Compared to slat-resistant(SR) subgroup, SS showed low urinary ET-1 excretion in normotensive group (P<0.05) or hypertensive group (P<0.01) ,regardless of saline loading or not. The nighttime MAP of SS was higher than SR subgroup in normotensive or hypertensive group. Urinary sodium excretion during 4h of saline loading was significantly lower in SS than that in SR hypertensive patients (P<0. 05). Twenty-four-hour UAE of SS patients was higher than SR group (P<0.01). Results of further correlation analysis indicated that the urinary ET-1 excretion was positively related to urinary sodium content and negatively to ABP and UAE. Conclusion Urinary ET-1 is low in SS normotensives or hypertension patients,which may play a role in renal sodium retention and renal impairment of SS hypertension patients.

  11. 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.

  12. Alkalosis and renal excretion of ammonia by rat kidney.

    Science.gov (United States)

    Solomon, S

    1988-05-15

    Upon sulfate administration, UpH falls more in alkalotic rats than in controls. Alkalosis can lead to a reduction in UNH3 V at highly acidic urine. The significance of this process is doubtful at UpH ranging from about 6 to 7. At lower UpH less NH3 would be excreted, thereby less H+ would be trapped in urine and some acid would be conserved.

  13. Effects of magnesium infusion on renal calcium excretion

    Energy Technology Data Exchange (ETDEWEB)

    Shafik, I.M.

    1986-01-01

    The effect of acute I.V. infusion of Mg on Ca excretion was investigated. Mg infusion resulted in a significantly increased urinary Ca excretion compared to the control group. The hypercalciuric effect of Mg was not accompanied by diuresis or natriuresis but was associated with significantly increased urinary Ca concentration suggesting a specific effect of Mg on urinary Ca excretion. The effect of 4mM MgCl/sub 2/ infusion on plasma Ca concentrations was also investigated. A comparable calciuric effect was again observed in the Mg infused group and was found to be associated with a significantly reduced whole kidney filtered load and absolute and fractional reabsorption of Ca. Intratubular microinjection experiments were performed to investigate the direct effects of raising Mg concentration on the unidirectional reabsorptive flux of (/sup 45/Ca). The unidirectional reabsorption of Ca injected into PCT was measured during four experimental conditions; with an d without Mg in the injectate solution during either saline or Mg infusion. Raising the intraluminal Mg significantly decreased unidirectional reabsorption of (/sup 45/Ca).

  14. Genetic variation underlying renal uric acid excretion in Hispanic children: The Viva La Familia Study

    Science.gov (United States)

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic...

  15. Cytostatic drugs are without significant effect on digitoxin plasma level and renal excretion.

    Science.gov (United States)

    Kuhlmann, J; Wilke, J; Rietbrock, N

    1982-11-01

    In three patients with malignant lymphoma who received 0.5 mg digitoxin before and 24 hr after combination therapy with cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, Oncovin, and prednisone (COP), plasma glycoside concentrations and renal excretion were measured 0 to 168 hr after digitoxin and the areas under plasma concentration-time curves *(AUCs) were calculated. In 10 patients receiving 0.1 mg digitoxin, daily plasma glycoside concentration and daily renal excretion were measured before and after COPP, COP, or cyclophosphamide, Oncovin, cytosine-arabinoside, and prednisone (COAP) treatment schemes. In contrast to previous reports on digoxin, cytostatic drug therapy does not lead to a reduction in steady-state digitoxin plasma levels and daily renal excretion. During cytostatic therapy attainment of peak digitoxin level was delayed after a single dose, showing that the rate of digitoxin absorption was reduced, but that the AUCs and renal excretion of digitoxin (parameters of the extent of digitoxin absorption) were not diminished. Since the absorption rate is not clinically relevant in patients on long-term glycoside therapy, our results indicate that digitoxin is preferable to digoxin in such patients.

  16. A novel description of FDG excretion in the renal system: application to metformin-treated models

    Science.gov (United States)

    Garbarino, S.; Caviglia, G.; Sambuceti, G.; Benvenuto, F.; Piana, M.

    2014-05-01

    This paper introduces a novel compartmental model describing the excretion of 18F-fluoro-deoxyglucose (FDG) in the renal system and a numerical method based on the maximum likelihood for its reduction. This approach accounts for variations in FDG concentration due to water re-absorption in renal tubules and the increase of the bladder’s volume during the FDG excretion process. From the computational viewpoint, the reconstruction of the tracer kinetic parameters is obtained by solving the maximum likelihood problem iteratively, using a non-stationary, steepest descent approach that explicitly accounts for the Poisson nature of nuclear medicine data. The reliability of the method is validated against two sets of synthetic data realized according to realistic conditions. Finally we applied this model to describe FDG excretion in the case of animal models treated with metformin. In particular we show that our approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin.

  17. Species variations among primates in responses to drugs which alter the renal excretion of uric acid.

    Science.gov (United States)

    Fannelli, G M; Weiner, I M

    1975-05-01

    The effects of salicylate, probenecid (Benemid) and pyrazinoate on uric acid excretion were determined in clearance experiments in the chimpanzee and Cebus monkey (C. albifrons and C. apella). The results were correlated with data from these species in the literature and where possible to analogous data in man. With salicylate, the rank order of responsiveness in terms of uricosuric action was chimpanzee greater than man greater than C. albifrons = C. apella. This was true when comparisons were made on the bases of drug concentration in plasma or the rate of drug excretion per milliliter of glomerular filtrate. A similar rank order was obtained with probenecid except that C. albifrons was slightly more responsive than C. apella. The latter comparisons were on the basis of plasma concentration of drug. The chimpanzee is more susceptible to the uricosuric action of pyrazinoate than is C. apella. With salicylate and pyrazinoate, there was urate retention at levels lower than those required for a uricosuric effect. The results suggest that in comparison with man, the chimpanzee is a hyperresponder to uricosuric drugs and Cebus monkeys are hyporesponders. Therefore, these findings limit extensions of quantitative results from one species to another.

  18. Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia.

    Science.gov (United States)

    Bishop, Jesse M; Lee, Hyun-Wook; Handlogten, Mary E; Han, Ki-Hwan; Verlander, Jill W; Weiner, I David

    2013-02-15

    The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is an ammonia-specific transporter heavily expressed in the kidney and is necessary for the normal increase in ammonia excretion in response to metabolic acidosis. Hypokalemia is a common clinical condition in which there is increased renal ammonia excretion despite the absence of metabolic acidosis. The purpose of this study was to examine Rhbg's role in this response through the use of mice with intercalated cell-specific Rhbg deletion (IC-Rhbg-KO). Hypokalemia induced by feeding a K(+)-free diet increased urinary ammonia excretion significantly. In mice with intact Rhbg expression, hypokalemia increased Rhbg protein expression in intercalated cells in the cortical collecting duct (CCD) and in the outer medullary collecting duct (OMCD). Deletion of Rhbg from intercalated cells inhibited hypokalemia-induced changes in urinary total ammonia excretion significantly and completely prevented hypokalemia-induced increases in urinary ammonia concentration, but did not alter urinary pH. We conclude that hypokalemia increases Rhbg expression in intercalated cells in the cortex and outer medulla and that intercalated cell Rhbg expression is necessary for the normal increase in renal ammonia excretion in response to hypokalemia.

  19. Urate-2-14C transport in the rat nephron

    Science.gov (United States)

    Kramp, Ronald A.; Lassiter, William E.; Gottschalk, Carl W.

    1971-01-01

    Intrarenal transport of urate-2-14C was studied in anesthetized rats using the microinjection technic. During saline diuresis, small volumes of urate-2-14C (0.24-0.48 mM) and inulin-3H were injected into surface proximal and distal convoluted tubules, and ureteral urine was collected serially. Total (74-96%) and direct (57-84%) urate recovery increased significantly the more distal the puncture site. Delayed recovery (±20%) remained approximately the same regardless of localization of the microinjection. After proximal injections, total and direct recoveries of urate-2-14C were significantly higher in rats treated with probenecid, pyrazinoate, or PAH than during saline diuresis alone, while the excretion rates were comparable after distal injection. Delayed recovery was not altered by drug administration. The decreased proximal reabsorption of urate is presumably due to an effect of the drugs on the luminal membrane of the nephron. For perfusion at high urate concentrations, nonradioactive urate was added to the injectate (0.89-1.78 mM). Urate-2-14C recovery was almost complete and there was no delayed excretion, demonstrating saturation kinetics. These findings are compatible with a carrier-mediated mechanism for urate transport probably located at the luminal border of the proximal tubular epithelium. No definitive evidence for urate secretion was found in these studies. PMID:5543881

  20. Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion?

    Science.gov (United States)

    Wikner, J; Wetterberg, L; Röjdmark, S

    1997-05-01

    Patients with primary hyperparathyroidism have higher serum melatonin concentrations during active disease than after surgical cure. Whether this is caused by hypercalcaemia per se, increased parathyroid hormone secretion or other mechanisms is unknown. We decided to elucidate whether exogenous hypercalcaemia influences melatonin secretion. For this purpose, eight healthy volunteers were infused with calcium and saline on separate days and in random order (experiment A). Hypercalcaemia inhibited nocturnal melatonin secretion by 20% but left urinary melatonin excretion unaffected. If exogenous hypercalcaemia inhibits melatonin secretion, it is reasonable to assume that calcium channel blockers such as verapamil might have the opposite effect. This was investigated in experiment B, in which eight healthy subjects were treated on separate occasions with oral verapamil and placebo. Verapamil did not affect nocturnal melatonin secretion but increased melatonin excretion by 145%. As 6-sulphatoxy-melatonin is the main melatonin metabolite excreted by the kidneys, it was considered important to find out whether verapamil would also influence the excretion of 6-sulphatoxy-melatonin. This was investigated in experiment C, in which eight healthy volunteers were treated, on separate occasions, with oral verapamil and placebo. In this experiment also, verapamil increased urinary melatonin excretion significantly (by 67%), but left excretion of 6-sulphatoxy-melatonin unaffected. These findings imply that verapamil influences the renal and/or hepatic handling of melatonin.

  1. Arterial blood pressure and renal sodium excretion in dopamine D3 receptor knockout mice.

    Science.gov (United States)

    Staudacher, Torsten; Pech, Bärbel; Tappe, Michael; Gross, Gerhard; Mühlbauer, Bernd; Luippold, Gerd

    2007-01-01

    Alterations in the dopaminergic system may contribute to the development of hypertension. Recently, it has been reported that pentobarbital-anesthetized mice with deficient dopamine D(3) receptors showed renin-dependent elevation in blood pressure. In a series of experiments, we evaluated the contribution of the dopamine D(3) receptor to the renal sodium excretion and arterial blood pressure behavior in conscious as well as anesthetized dopamine D(3) receptor knockout (-/-) mice. The blood pressure measuring study was designed as a cross-over trial to investigate the influence of different sodium loads. The animals were fed a normal salt diet (0.6% NaCl, NS) for 1 week and afterwards a low (0.2% NaCl, LS) or a high salt diet (4.6% NaCl, HS) for 2 weeks. After the third week, the animals were switched to the corresponding protocol. Systolic blood pressure in conscious (-/-) mice measured by tail-cuff plethysmography was not different from that of wild-type (+/+) animals, irrespective of the time course or the salt diet. In another experiment, challenge of an acute sodium loading per gavage in conscious D(3) receptor (-/-) and (+/+) animals on HS or NS diet did not show significant differences in renal sodium excretion between the two genotypes. Additionally, animals were fed an NS diet for 1 week and an HS diet for another week. As expected, sodium excretion significantly increased after the change from the NS to the HS diet. A slightly lower urinary sodium excretion was observed when comparing D(3) receptor (-/-) mice to their corresponding (+/+) mice, both on an HS diet. Clearance experiments with anesthetized D(3) receptor (-/-) and (+/+) mice were performed to investigate the renal sodium excretion capacity, when exposed to a moderate volume expansion (VE). Urinary sodium excretion increased in response to the VE; however, no difference were observed between the two genotypes. Taking these results together, we conclude that in the present animal model renal

  2. Renal function, aldosterone, and vasopressin excretion following repeated long-distance running.

    Science.gov (United States)

    Wade, C E; Dressendorfer, R H; O'Brien, J C; Claybaugh, J R

    1981-04-01

    Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

  3. Mechanisms regulating the renal excretion of sodium during pregnancy.

    Science.gov (United States)

    Robb, C A; Davis, J O; Johnson, J A; Blaine, E H; Schneider, E G; Baumber, J S

    1970-05-01

    Observations were made on the relation of the renin-angiotensin-aldosterone system and renal hemodynamic function to sodium balance in 43 pregnant dogs. Daily balance studies revealed that about 30-40% of ingested sodium was retained during the last half of pregnancy; during the same period, potassium balance was also positive but to a lesser extent. For groups of pregnant dogs, plasma renin activity (n = 14) and aldosterone secretion (n = 19) were significantly higher than normal; however, in some animals one or both functions were normal even though sodium retention was present. In contrast, plasma renin substrate concentration was consistently elevated during pregnancy in seven dogs. In a group of nine dogs in which both aldosterone secretion and plasma renin activity were measured, aldosterone secretion was elevated in the three dogs with the highest values for plasma renin activity; in two of the remaining six animals aldosterone secretion was elevated but plasma renin activity was normal or only slightly increased. The sequestration of sodium and water into the uterine contents was defined quantitatively in this study but evidence was lacking to support the idea that such changes led to renin release. The glomerular filtration rate (GFR) was significantly elevated throughout pregnancy but a significant decrease from the high level of mid-pregnancy occurred during the last half of pregnancy; this decrease in GFR probably contributed to the sodium retention. Administration of a large dose of deoxycorticosterone acetate (DOCA) to dogs in late pregnancy produced marked sodium retention but "escape" from the sodium-retaining steroid occurred. The data demonstrate that although increased activity of the renin-angiotensin-aldosterone system was frequently present during pregnancy, a normal rate of aldosterone secretion occurred. This finding and the observed "escape" from DOCA suggest the existence of sodium-retaining mechanisms other than the mechanism provided by

  4. Renal pathology and urinary protein excretion in a 14-month-old Bernese mountain dog with chronic renal failure.

    Science.gov (United States)

    Raila, J; Aupperle, H; Raila, G; Schoon, H-A; Schweigert, F J

    2007-04-01

    The renal pathology and urinary protein pattern of a 14-month-old female Bernese mountain dog with chronic renal failure was investigated. Sodium dodecyl sulphate-polyacrylamid gel electrophoresis and subsequent Western blot analysis of urine showed the presence of heavy and light chains of immunoglobulin, transferrin, albumin, vitamin D-binding protein, transthyretin and retinol-binding protein (RBP), but no excretion of Tamm-Horsfall protein (THP). Histopathological examinations of the kidneys revealed severe membranous glomerulonephritis accompanied by tubular dilatation, tubular atrophy and interstitial fibrosis. The renal expression of megalin, the main endocytic receptor for the re-uptake of proteins in proximal tubules, RBP and THP was reduced or completely absent, indicating severe tubular dysfunction. The identified urinary proteins may be of interest as additional markers for the diagnosis of juvenile nephropathy in Bernese mountain dogs.

  5. 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.

  6. Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin.

    Science.gov (United States)

    Kuhlmann, J; Zilly, W; Wilke, J

    1981-10-01

    Mucosal defects decrease digoxin absorption in patients with malabsorption syndromes. Since the intestinal mucosa can be damaged by cytostatic drugs, we investigated their effects on digoxin plasma levels and urinary digoxin excretion. In six patients with malignant lymphoma who received 0.8 mg beta-acetyldigoxin before and 24 hr after treatment with a combination of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, oncovin, and prednisone (COP), plasma digoxin concentrations were measured 0 to 8 hr after the dose and areas under the plasma concentration-time curves were calculated. In 15 patients on 0.3 mg of beta-acetyldigoxin daily, plasma glycoside concentrations and renal excretion were measured daily before and after COPP, COP, cyclophosphamide, oncovin, cytosine-arabinosine, and prednisone (COAP), or adriamycin, bleomycin, and prednisone (ABP) treatment schemes. The diminished steady-state glycoside plasma concentrations and daily renal glycoside excretion during the 24 to 168 hr after the cytostatic drug established reversible impairment of digoxin absorption. The delayed time to peak after a single dose of digoxin during cytostatic drug therapy shows that extent and rate of digoxin absorption are reduced. To maintain adequate control of digoxin therapy in patients treated with cytostatic drugs, plasma levels should be monitored.

  7. Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    2010-01-01

    Increased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients...... with type 2 diabetes and normal or increased UOER....

  8. Relationship between urinary prostaglandin E2 and F2 alpha excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Christensen, P; Danielsen, H; Eiskjaer, H; Jespersen, B; Knudsen, F; Kornerup, H J; Leyssac, P P; Nielsen, A H; Sørensen, S S

    1987-10-01

    Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.

  9. Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

    Science.gov (United States)

    Bataillard, A; Blanc-Brunat, N; Vivier, G; Medeiros, I; Zhang, B L; Touraine, J L; Sassard, J

    1996-02-01

    The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

  10. Impaired renal function and increased urinary isoprostane excretion in Ghanaian women with pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Tetteh PW

    2013-06-01

    Full Text Available Paul Winston Tetteh,1,4 Charles Antwi-Boasiako,1 Ben Gyan,3 Daniel Antwi,1 Festus Adzaku,1 Kwame Adu-Bonsaffoh,1,2 Samuel Obed21Department of Physiology, 2Department of Obstetrics and Gynecology, University of Ghana Medical School, Accra, Ghana; 3Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana; 4Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, The NetherlandsBackground: The cause of pre-eclampsia remains largely unknown, but oxidative stress (an imbalance favoring oxidant over antioxidant forces has been implicated in contributing to the clinical symptoms of hypertension and proteinuria. Assessment of oxidative stress in pre-eclampsia using urinary isoprostane has produced conflicting results, and it is likely that renal function may affect isoprostane excretion. The aim of this study was to determine the role of oxidative stress in the pathophysiology of pre-eclampsia and to assess the effect of renal function on isoprostane excretion in pre-eclampsia in the Ghanaian population.Methods: This was a case-controlled study, comprising 103 pre-eclamptic women and 107 normal pregnant controls and conducted at the Korle-Bu Teaching Hospital between December 2006 and May 2007. The study participants were enrolled in the study after meeting the inclusion criteria and signing their written informed consent. Oxidative stress was determined by measuring urinary excretion of isoprostane and total antioxidant capacity using an enzyme-linked immunosorbent assay technique. Renal function was assessed by calculating the estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula.Results: The pre-eclampsia group had significantly (P = 0.0006 higher urinary isoprostane excretion (2.81 ± 0.14 ng/mg creatinine than the control group (2.01 ± 0.18 ng/mg creatinine and a significantly (P = 0.0008 lower total antioxidant power (1

  11. Chronic effects of lead on renin and renal sodium excretion. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, N.; Mouw, D.R.; Vander, A.J.

    1980-05-01

    Rats were chronically give 0.5 mg/ml Pb in drinking water. This produced blood and renal lead concentratoins of approximately 30 )g/dl and 20)g/gm, respectively, significant kidney swelling, but no change in body weight or hematocrit. After 6 weeks of Pb treatment and during ingestion of a sodium-free diet, plasma, renin activity (PRA) was elevated (controls: same diet, no lead), but there was no change in plasma resin substrate (PRS). After 5 months the PRA was significantly higher in the lead-treated group even on a 1% NaCl diet, but the difference between groups disappeared on an Na-free diet; that is, the renin response to sodium deprivation was blunted. As early as 6 weeks after beginning lead treatment, the treated group manifested reduced ability to decrease Na excretion following removal of NaCl from the diet; steady-state sodium excretion was normal on either the 1% NaCl or Na-free diet. We conclude that changes in the renin angiotensin system and renal sodium handling may be important toxic effects of low doses of lead on the kidneys of rats.

  12. Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion.

    Science.gov (United States)

    Lee, Hyun-Wook; Verlander, Jill W; Bishop, Jesse M; Handlogten, Mary E; Han, Ki-Hwan; Weiner, I David

    2013-02-15

    The Rhesus factor protein, Rh C glycoprotein (Rhcg), is an ammonia transporter whose expression in the collecting duct is necessary for normal ammonia excretion both in basal conditions and in response to metabolic acidosis. Hypokalemia is a common clinical condition associated with increased renal ammonia excretion. In contrast to basal conditions and metabolic acidosis, increased ammonia excretion during hypokalemia can lead to an acid-base disorder, metabolic alkalosis, rather than maintenance of acid-base homeostasis. The purpose of the current studies was to determine Rhcg's role in hypokalemia-stimulated renal ammonia excretion through the use of mice with collecting duct-specific Rhcg deletion (CD-Rhcg-KO). In mice with intact Rhcg expression, a K(+)-free diet increased urinary ammonia excretion and urine alkalinization and concurrently increased Rhcg expression in the collecting duct in the outer medulla. Immunohistochemistry and immunogold electron microscopy showed hypokalemia increased both apical and basolateral Rhcg expression. In CD-Rhcg-KO, a K(+)-free diet increased urinary ammonia excretion and caused urine alkalinization, and the magnitude of these changes did not differ from mice with intact Rhcg expression. In mice on a K(+)-free diet, CD-Rhcg-KO increased phosphate-dependent glutaminase (PDG) expression in the outer medulla. We conclude that hypokalemia increases collecting duct Rhcg expression, that this likely contributes to the hypokalemia-stimulated increase in urinary ammonia excretion, and that adaptive increases in PDG expression can compensate for the absence of collecting duct Rhcg.

  13. Association between urinary albumin excretion and intraocular pressure in type 2 diabetic patients without renal impairment.

    Directory of Open Access Journals (Sweden)

    Jin A Choi

    Full Text Available BACKGROUND: To assess the relationship between urinary albumin excretion and intraocular pressure (IOP in type 2 diabetes patients without renal impairment. METHODS: We explored the effects of albuminuria on high IOP in 402 non-glaucomatous type 2 diabetes without renal impairment who participated in the 2011 Korean National Health and Nutrition Examination Survey (KNHANES. Multiple logistic regression analysis was used to assess the relationship between log-transformed albumin/creatinine ratio (ACR tertiles and an IOP of ≥ 18 mmHg after adjusting for age, gender, hypertension, body mass index, triglycerides, area of residence, and education level. RESULTS: Subjects with a high IOP ≥ 18 mmHg were more likely to be current smokers (P = 0.038, heavy drinkers (P = 0.006, and to have high systolic blood pressure (P = 0.016, triglycerides (P = 0.008, and a higher log-transformed ACR (P = 0.022.In multivariate regression analysis, ACR tertile was associated with the prevalence of high IOP significantly (P = 0.022. The associations between ACR tertiles and high IOP were significant in overweight patients and those with abdominal obesity (P = 0.003 and 0.003, respectively. In contrast, there were no associations in the subgroup of patients who were not overweight and those without abdominal obesity (P = 0.291 and 0.561, respectively. CONCLUSIONS: Urinary albumin excretion is associated with high IOP in the type 2 diabetes population without renal insufficiency. The effect of the albuminuria on IOP was evident in a subgroup of patients with components of metabolic syndrome.

  14. Generation of mouse anti-human urate anion exchanger antibody by genetic immunization and its identification

    Institute of Scientific and Technical Information of China (English)

    XU Guo-shuang; WU Di; CHEN Xiang-mei; SHI Suo-zhu; HONG Quan; ZHANG Ping; LU Yang

    2005-01-01

    Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney.Methods Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody’s generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry.Results The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58kD hURAT1 and 64kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody

  15. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

    Directory of Open Access Journals (Sweden)

    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  16. 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.

  17. Comparative effects of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.

    Science.gov (United States)

    Takahashi, Y; Funakoshi, T; Shimada, H; Kojima, S

    1994-05-31

    The effects of various chelating agents, such as (2S)-1-(3-mercaptopropionyl)-L-proline (captopril), N-(2-mercaptopropionyl)-glycine (tiopronin), L-cysteine (L-Cys), D-cysteine (D-Cys), N-acetyl-L-cysteine (L-NAC), N-benzyl-D-glucamine dithiocarbamate (BGD), and ethylenediaminetetraacetate (EDTA), on the distribution, excretion, and renal toxicity of gold sodium thiomalate (AuTM) in rats were investigated. Rats were intraperitoneally injected with the chelating agents (1.2 mmol/kg each) immediately after intravenous injection of AuTM (0.026 mmol/kg). Treatment with captopril or tiopronin significantly prevented increases in the urinary excretion of protein, aspartate aminotransferase (AST), and glucose and the blood urea nitrogen (BUN) level after AuTM injection. L-NAC and D-Cys significantly prevented increases in the urinary excretion of protein, AST, and glucose after AuTM injection, but did not reduce to control levels. Treatment with BGD, EDTA, or L-Cys did not prevent AuTM-induced increases in the urinary excretion of protein, AST, and glucose and BUN level. Tiopronin significantly increased the urinary excretion of gold. Captopril slightly promoted both the urinary and fecal excretion of gold, resulting in the significant increase in the total excretion of the metal. Tiopronin and captopril significantly decreased the gold concentration in the kidney and liver. L-Cys, D-Cys, L-NAC, BGD, and EDTA had no significant effect on the excretion or distribution of gold at 7 days after AuTM injection. These results indicate that tiopronin and captopril can ameliorate the renal toxicity induced by AuTM. In addition, the comparative effects of 2,3-dimercaptopropane sulfonate (DMPS), N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), captopril, and tiopronin at various dose levels (1.2, 0.4 or 0.2 mmol/kg) on the distribution and renal toxicity of gold were studied. DMPS was effective in removing gold from the kidney and in protecting against the renal toxicity

  18. Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout

    Science.gov (United States)

    Tan, Philip K.; Farrar, Jennifer E.; Gaucher, Eric A.; Miner, Jeffrey N.

    2016-01-01

    Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27–77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors. PMID:27352852

  19. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning......, diagnosis, and treatment....

  20. Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma

    DEFF Research Database (Denmark)

    Hansen, P B; Dalhoff, K; Joffe, P

    1991-01-01

    The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m...... excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were...

  1. Urinary potassium excretion and risk of developing hypertension: the prevention of renal and vascular end-stage disease study.

    Science.gov (United States)

    Kieneker, Lyanne M; Gansevoort, Ron T; Mukamal, Kenneth J; de Boer, Rudolf A; Navis, Gerjan; Bakker, Stephan J L; Joosten, Michel M

    2014-10-01

    Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of this association. Risk of hypertension (defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and midway during follow-up (2001-2003). Baseline median potassium excretion was 70 mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The lowest sex-specific tertile of potassium excretion (men: hypertension after multivariable adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%-10.9%). No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment. Low urinary potassium excretion was associated with an increased risk of developing hypertension. Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension.

  2. Renal Fractional Excretion of Sodium in Relation to Arterial Blood Gas and Spirometric Parameters in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Fariba Rezaeetalab

    2014-05-01

    Full Text Available Introduction: Arterial gas derangement could change urinary sodium excretion in Chronic Obstructive Pulmonary Disease (COPD patients.There are very few and conflicting data in regards to the measurement of fractional excretion of sodium in COPD patients. The main aim of this study was to assess the relationship between renal fractional excretion of sodium(FeNa with arterial blood gas and spirometric parameters in COPD. Materials and Methods: This study was a cross-sectional study performed on 40 consecutive stable COPD outpatients in 2 main general hospitals (Emam Reza, Ghaem in Mashhad/Iran between 2011 and 2012. We investigated the relationship of renal FeNa with arterial blood gas parameters including HCO3, PH, PaCO2 and PaO2, and spirometric parameters. Analysis was done by SPSS v16 with a statistically meaningful p value of less than 0.05. Results: Mean age was 65.97±10.77 SD years and female to male ratio was 0.26. A renal FeNa of less than 1% was presented in 27% patients. There was a significant, positive relationship between renal FeNa and PaO2 (P=0.005, r=0.456. The correlations between PaCO2, HCO3, PH and spirometric parameters were not seen (P>0.05, but there was a significant relationship between Urine Na and PaO2. Outstanding, it seems likely that kidneys of COPD patients are responsible for sodium retaining state particularly in the presence of hypoxemia. Conclusion: This study indicates that in COPD patients, PaO2 but not PaCO2 is related to renal FeNa which shows the probable role of hypoxemia on sodium output in COPD patients. However, some caution is needed for interpretation of the probable role of hypercapnia on sodium retention in COPD.

  3. Renal Fractional Excretion of Sodium in Relation to Arterial Blood Gas and Spirometric Parameters in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Fariba Rezaeetalab

    2014-05-01

    Full Text Available Introduction: Arterial gas derangement could change urinary sodium excretion in Chronic Obstructive Pulmonary Disease (COPD patients.There are very few and conflicting data in regards to the measurement of fractional excretion of sodium in COPD patients. The main aim of this study was to assess the relationship between renal fractional excretion of sodium(FeNa with arterial blood gas and spirometric parameters in COPD. Materials and Methods: This study was a cross-sectional study performed on 40 consecutive stable COPD outpatients in 2 main general hospitals (Emam Reza, Ghaem in Mashhad/Iran between 2011 and 2012. We investigated the relationship of renal FeNa with arterial blood gas parameters including HCO3, PH, PaCO2 and PaO2, and spirometric parameters. Analysis was done by SPSS v16 with a statistically meaningful p value of less than 0.05. Results: Mean age was 65.97±10.77 SD years and female to male ratio was 0.26. A renal FeNa of less than 1% was presented in 27% patients. There was a significant, positive relationship between renal FeNa and PaO2 (P=0.005, r=0.456. The correlations between PaCO2, HCO3, PH and spirometric parameters were not seen (P>0.05, but there was a significant relationship between Urine Na and PaO2. Outstanding, it seems likely that kidneys of COPD patients are responsible for sodium retaining state particularly in the presence of hypoxemia. Conclusion: This study indicates that in COPD patients, PaO2 but not PaCO2 is related to renal FeNa which shows the probable role of hypoxemia on sodium output in COPD patients. However, some caution is needed for interpretation of the probable role of hypercapnia on sodium retention in COPD.

  4. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Directory of Open Access Journals (Sweden)

    Kristoffer Svensson

    Full Text Available The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.

  5. Renal excretion in coho salmon (Oncorhynchus kisutch) after acute exposure to 3-trifluoromethyl-4-nitrophenol

    Science.gov (United States)

    Hunn, J.B.; Allen, J.L.

    1975-01-01

    COHO SALMON (ONCORHYNCHUS KISUTCH) EXPOSED TO AN ACUTE, SUBLETHAL CONCENTRATION OF 3-TRIFLUOROMETHLY 1-4 NITROPHENOL (TFM) EXHIBITED AN INCREASED OUTPUT OF URINE WHEN COMPARED WITH CONTROLS, BUT THE URINARY EXCRETION OF NA, K, CA, MG AND C1 WAS NOT AFFECTED. ABOUT 35 TIMES MORE CONJUGATED TFM THAN FREE TFM WAS EXCRETED DURING THE 24-HOUR STUDY PERIOD.

  6. Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

    OpenAIRE

    Bobulescu, Ion Alexandru; Moe, Orson W.

    2012-01-01

    In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible f...

  7. 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

  8. Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity.

    Science.gov (United States)

    Oparil, S; Ehrlich, E N; Lindheimer, M D

    1975-08-01

    1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.

  9. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    Science.gov (United States)

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  10. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Nicolás M Kouyoumdzian

    Full Text Available The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP on organic cation transporters (OCTs expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T, ANP, dopamine (DA, D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects.

  11. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

    Directory of Open Access Journals (Sweden)

    Yusuke Okazaki

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

  12. 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...

  13. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Wetzels, J.F.M.; Joles, J.A.; Christensen, E.I.; Verroust, P.J.; Li, D.; Oliver, N.; Xu, L.; Kok, R.J.; Goldschmeding, R.

    2010-01-01

    Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal ex

  14. 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.

  15. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, N V; 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 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... 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...

  16. URAT Parallax Catalog (UPC)

    CERN Document Server

    Finch, Charlie

    2016-01-01

    The URAT Parallax Catalog (UPC) consists of 112,177 parallaxes. The catalog utilizes all Northern Hemisphere exposures from the United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT) obtained between April 2012 and June 2015. Relative parallaxes are converted to absolute using photometric distance estimates of UCAC4 reference stars. There are 2 groups of stars in this catalog: 1) 58,677 stars with prior published trigonometric parallax (Hipparcos, Yale Parallax Catalog, MEarth project and SIMBAD), and 2) 53,500 stars with first time trigonometric parallaxes as obtained from URAT data. More stringent selection criteria have been applied for group 2 then for group 1 in order to keep the rate of false detections low. The mean error in UPC parallaxes is 10.8 and 4.3 mas for groups 1 and 2, respectively. All stars in UPC are north of -13 deg Dec and between 6.5 and 17 mag. The UPC is published by CDS as catalog I/333 and the acronym has been registered with the IAU. The Finch & Zacharias (...

  17. Urinary excretion of epidermal growth factor and Tamm-Horsfall protein in three rat models with increased renal excretion of urine

    DEFF Research Database (Denmark)

    Thulesen, J; Jørgensen, P E; Torffvit, O

    1997-01-01

    Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP...

  18. Plasma levels and urinary excretion of amino acids by subjects with renal calculi.

    Science.gov (United States)

    Atanassova, Stoyanka Slavcheva; Panchev, P; Ivanova, M

    2010-05-01

    Plasma levels and urinary amino acid excretions were estimated by high-performance liquid chromatography in 15 control subjects and 36 stone formers (SFs) classified according to the stone type: (1) 22 cases with calcium oxalate stones; (2) four cases with pure uric acid stones; (3) 10 cases with magnesium-ammonium phosphate stones, either pure or mixed with apatite. Some types of stones (namely oxalate and uric acid calculi) are mainly formed as a result of a metabolic deficiency that may affect the amino acid metabolism, and thus may be reflected in the urinary amino acid pattern. Data demonstrated clearly that there is a general tendency towards decreased amino acid excretions in all SFs with all types of stones. As a whole, one can observe a higher percentage of patients with calcium oxalate and phosphate calculosis, who have low urine excretions of amino acids; about 50% are the SFs with lower urine excretion of serine, glycine, taurine and i-leucine; the high percentage of patients with CaOX calculi shows lower urine excretions of tyrosine and ornithine.

  19. Urinary potassium excretion, renal ammoniagenesis, and risk of graft failure and mortality in renal transplant recipients1-3

    NARCIS (Netherlands)

    Eisenga, Michele F.; Kieneker, Lyanne M.; Soedamah-Muthu, Sabita S.; Berg, Van Den Else; Deetman, Petronella E.; Navis, Gerjan J.; Gans, Reinold O.B.; Gaillard, Carlo A.J.M.; Bakker, Stephan J.L.; Joosten, Michel M.

    2016-01-01

    Background: Renal transplant recipients (RTRs) have commonly been urged to limit their potassium intake during renal insufficiency and may adhere to this principle after transplantation. Importantly, in experimental animal models, low dietary potassium intake induces kidney injury through stimula

  20. Usefulness of the renal resistive index to predict an increase in urinary albumin excretion in patients with essential hypertension.

    Science.gov (United States)

    Miyoshi, K; Okura, T; Tanino, A; Kukida, M; Nagao, T; Higaki, J

    2017-01-01

    Microalbuminuria is a risk factor for cardiovascular events and death in hypertensive patients. Patients who are expected to increase albuminuria need strict blood pressure control. In the present study, we assessed the association between the renal resistive index (RI) and future increases in albuminuria in patients with essential hypertension. Sixty-six patients with essential hypertension were included in the study. Univariate and multivariate logistic regression analyses were used to identify the factors, including renal RI, that were significant independent determinants of increased in urinary albumin excretion (UAE), defined as an increase of >50% in the urinary albumin-to-creatinine ratio over 2 years. Receiver operator characteristics curve analysis was used to select the optimal cut-off point that predicted an increase in UAE. RI was the only significant variable that predicted the increase in UAE, with the optimal cut-off value of renal RI that predicted this increase being 0.71 (sensitivity 52.4% and specificity 84.4%). Renal RI is associated with the future increase in albuminuria in patients with essential hypertension.

  1. Influence of urinary sodium excretion on the clinical assessment of renal tubular calcium reabsorption in hypercalcaemic man.

    Science.gov (United States)

    Ralston, S H; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1986-06-01

    The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.

  2. Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins.

    NARCIS (Netherlands)

    Hsu, Y.J.; Dimke, H.; Schoeber, J.P.H.; Hsu, S.C.; Lin, S.H.; Chu, P.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2010-01-01

    Although gender differences in the renal handling of calcium have been reported, the overall contribution of androgens to these differences remains uncertain. We determined here whether testosterone affects active renal calcium reabsorption by regulating calcium transport proteins. Male mice had hig

  3. Subcuticular urate accumulation in an American lobster (Homarus americanus).

    Science.gov (United States)

    Battison, A L

    2013-05-01

    An unusually "lumpy" lobster, Homarus americanus, was presented to the Atlantic Veterinary College Lobster Science Centre for evaluation. The lobster was weak with numerous pale, raised, and flat areas (diameter, 3-15 mm) on the exoskeleton, some of which were ulcerated. On postmortem examination, the pale areas corresponded to accumulations of viscous to free-flowing white material, which was found in only the subcuticular connective tissues. No internal organs were affected. Direct light examination of nonstained impression smears of the material showed abundant crystals resembling uric acid, amorphous urates, and sodium urate, which were readily soluble in 1 M potassium hydroxide. Wright-Giemsa stained imprints showed numerous fine, rounded, nonstaining granules free in the background and within individual round cells. Fourier-transformed infrared spectroscopy confirmed the presence of urates or mixed urate salts. Hemolymph plasma urea (1.7 mmol/liter) and uric acid (287 μmol/liter) concentrations were slightly higher than those seen with 36-hour emersion. Histologic sections showed aggregates of vacuolated mononuclear cells in the loose subcuticular connective tissue occasionally infiltrating between underlying muscle fibers. Grossly visible urate deposits are occasionally documented in land crabs and rarely reported in the blue crab; none, however, are associated with deformation of the cuticle. Possible etiologies include increased uric acid intake or production or decreased excretion. Anecdotal reports of similarly affected lobsters have been received but are intermittent and undocumented.

  4. The clinical significance of disordered renal excretion of xanthurenic acid in depressive patients.

    Science.gov (United States)

    Hoes, M J; Sijben, N

    1981-01-01

    Xanthurenic acid is a metabolite of L-tryptophanicotinic acid ribonucleotide biosynthesis. The excretion of xanthurenic acid from urine 24 h after ingestion of 5 g L-tryptophan is increased in depressive patients, and 17-hydroxycorticosteroids are considered of primary importance to this disorder. However, in this study, the excretion of xanthurenic acid and 17-hydroxycorticosteroids did not correlate with the scores of the Raskin depression scale, Hamilton depression scale, Zung depression scale, or the Zung anxiety scale in depressive patients. The patients were treated with either pyridoxine plus L-tryptophan, a presumably serotonin-enhancing treatment (n = 10) or maprotiline, a noradrenaline-enhancing drug (n = 10). Repeated measurements showed no differences between treatments after 2 or 4 weeks of treatment. The improvement in xanthurenic acid excretion precedes clinical improvements in depression. The excretion of xanthurenic acid only at 2 weeks correlated significantly with the anxiety and depression scores at 4 weeks, making prediction of clinical improvement possible. The neurobiological mode of action on noradrenergic or serotonergic neurons of antidepressant medication is of questionable significance to their therapeutic effect.

  5. Prevalence of URAT1 allelic variants in the Roma population.

    Science.gov (United States)

    Stiburkova, Blanka; Gabrikova, Dana; Čepek, Pavel; Šimek, Pavel; Kristian, Pavol; Cordoba-Lanus, Elizabeth; Claverie-Martin, Felix

    2016-12-01

    The Roma represents a transnational ethnic group, with a current European population of 8-10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians. However, RHUC 1 patients have been described in a variety of ethnic groups (e.g., Arab Israelis, Iraqi Jews, Caucasians, and Roma) and in geographically noncontiguous countries. This study confirms our previous findings regarding the high frequency of SLC22A12 variants observed. Frequencies of the c.1245_1253del and c.1400C>T variants were found to be 1.92% and 5.56%, respectively, in a subgroup of the Roma population from five regions in three countries: Slovakia, Czech Republic, and Spain. Our findings suggested that the common dysfunction allelic variants of URAT1 exist in the general Roma population and thus renal hypouricemia should be kept in differential diagnostic algorithm on Roma patients with defect in renal tubular urate transport. This leads to confirm that the genetic drift in the Roma have increased the prevalence of hereditary disorders caused by very rare variants in major population.

  6. Urinary excretion of albumin and beta-2-microglobulin in hypertensive and normotensive renal transplant recipients during urinary diluting and concentrating tests.

    Science.gov (United States)

    Jespersen, B; Pedersen, E B; Danielsen, H; Kornerup, H J; Knudsen, F; Mogensen, C E; Nielsen, A H

    1986-11-01

    Urinary excretion of albumin and beta-2-microglobulin was measured in nine hypertensive and nine normotensive renal transplant recipients and 10 healthy control subjects before and after an oral water load of 20 ml (kg body weight)-1 (study 1) and in eight hypertensive and 11 normotensive renal transplant recipients and 11 healthy control subjects during 24-h water deprivation (study 2). In both studies 1 and 2 urinary albumin excretion was significantly higher (p less than 0.01) in the hypertensive renal transplant recipients that in the normotensive patients and the control subjects (levels before loading; hypertensives: 23.9 micrograms/min (median), range 7.5-58.7; normotensives: 3.4 micrograms/min, range 1.0-49.3; controls: 2.9 micrograms/min, range 1.3-10.3). Urinary albumin excretion was significantly positive correlated to both systolic, diastolic and mean blood pressure (for mean blood pressure: rho = 0.625, n = 18, p less than 0.01) in transplanted patients. Albumin excretion tended to increase after water loading and to decrease during water deprivation in all groups. Beta-2-microglobulin excretion was approximately the same in all groups in both studies 1 and 2 and was not correlated to blood pressure. During a follow-up period of at least 18 months, none of the renal transplant recipients developed signs of chronic graft failure. Increased urinary albumin excretion in hypertensive renal transplant recipients thus appears to be caused by increased glomerular permeability that may be due to glomerular damage induced by arterial hypertension corresponding to the findings in essential hypertension.

  7. Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, C.C.S. [Disciplina de Nefrologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Tovar, A.M.F. [Laboratório de Tecido Conjuntivo, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Guimarães, M.A.M. [Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Bregman, R. [Disciplina de Nefrologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

    2013-08-10

    Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

  8. Renal fluoride excretion in children following topical application of fluoride varnish.

    Science.gov (United States)

    García-Hoyos, F; Barbería, E; García-Camba, P; Varela, M

    2012-12-01

    To demonstrate that the application of dental fluoride varnishes in children increases urinary fluoride excretion. From a randomly assembled group of 42 children aged between 5 and 8 years, residing in a community with non-fluoridated water, spot urinary samples were taken before the topical application of dental fluoride varnish and 2 hours afterwards. In an age-matched control group of 16 children from the same community, who received no treatment, samples were taken the same way. The urinary excretion of fluoride was analysed by determining fluoride ion (F-) level and fluoride/creatinine (F/Cr) ratio in the urine. In the study group, the average pre- and post-treatment F/Cr ratios were 0.42 and 1.38 mg/g, respectively (p fluoride varnish leads to a significant increase in urine F-, which is attributable to the application of the product.

  9. Renal excretion of vanillylmandelic acid and homovanillic acid in rats with paw edema or adjuvant arthritis.

    Science.gov (United States)

    Krause, E; Horn, M

    1982-01-01

    1. Urinary excretion of unconjugated vanillylmandelic acid (VMA) and homovanillic acid (HVA) was found to be decreased in adjuvant arthritic rats. The decrease is apparently not due to impaired animal activity, but it could be explained by the reduction of catecholamine biosynthesis and/or release induced by E prostaglandins the biosynthesis of which is increased in the inflammation. It could also be caused by an increased "consumption" of catecholamines during prostaglandin biosynthesis. 2. Both the reduction of biosynthesis or release and an increased "consumption" of catecholamines would mean that inflammation is characterized by deficiency of the anti-inflammatory catecholamines. 3. The investigations failed to demonstrate an adequate decrease of the urinary excretion of VMA and HVA in rats with edemas induced by carrageenin, serotonin, formaline, silver nitrate, kaolin, dextran and baker's yeast, respectively. The experiments should be repeated with other catecholamine metabolites.

  10. Rh versus pH: the role of Rhesus glycoproteins in renal ammonia excretion during metabolic acidosis in a freshwater teleost fish.

    Science.gov (United States)

    Wright, Patricia A; Wood, Chris M; Wilson, Jonathan M

    2014-08-15

    Increased renal ammonia excretion in response to metabolic acidosis is thought to be a conserved response in vertebrates. We tested the hypothesis that Rhesus (Rh) glycoproteins in the kidney of the freshwater common carp, Cyprinus carpio, play a crucial role in regulating renal ammonia excretion during chronic metabolic acidosis. Exposure to water pH 4.0 (72 h) resulted in a classic metabolic acidosis with reduced plasma arterial pH and [HCO3(-)], no change in PCO2 and large changes in renal function. Urine [NH4(+)] as well as [titratable acidity-HCO3(-)] rose significantly over the acid exposure, but the profound reduction (fivefold) in urine flow rates eliminated the expected elevations in renal ammonia excretion. Low urine flow rates may be a primary strategy to conserve ions, as urinary excretion rates of Na(+), Cl(-) and Ca(2+) were significantly lower during the acid exposure relative to the control period. Interestingly, renal Rhcg1 mRNA and protein levels were elevated in acid-exposed relative to control groups, along with mRNA levels of several ion transporters, including the Na(+)/H(+) exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. Immunofluorescence microscopy showed a strong apical Rhcg1 signal in distal tubules. Taken together, these data show that renal Rh glycoproteins and associated ion transporters are responsive to metabolic acidosis, but conservation of ions through reduced urine flow rates takes primacy over renal acid-base regulation in the freshwater C. carpio. We propose that an 'acid/base-ion balance' compromise explains the variable renal responses to metabolic acidosis in freshwater teleosts.

  11. Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man.

    Science.gov (United States)

    Hasler, Felix; Bourquin, Daniel; Brenneisen, Rudolf; Vollenweider, Franz X

    2002-09-01

    In a clinical study eight volunteers received psilocybin (PY) in psychoactive oral doses of 212+/-25 microg/kg body weight. To investigate the elimination kinetics of psilocin (PI), the first metabolite of PY, urine was collected for 24 h and PI concentrations were determined by high-performance liquid chromatography with column switching and electrochemical detection (HPLC-ECD). Sample workup included protection of the unstable PI with ascorbic acid, freeze-drying, and extraction with methanol. Peak PI concentrations up to 870 microg/l were measured in urine samples from the 2-4 h collection interval. The PI excretion rate in this period was 55.5+/-33.8 microg/h. The limit of quantitation (10 microg/L) was usually reached 24 h after drug administration. Within 24 h, 3.4+/-0.9% of the applied dose of PY was excreted as free PI. Addition of beta-glucuronidase to urine samples and incubation for 5 h at 40 degrees C led to twofold higher PI concentrations, although 18+/-7% of the amount of unconjugated PI was decomposed during incubation. We conclude that in humans PI is partially excreted as PI-O-glucuronide and that enzymatic hydrolysis extends the time of detectability for PI in urine samples.

  12. The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Jiang

    Full Text Available Renal dopamine D1-like receptors (D1R and D5R and the gastrin receptor (CCKBR are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake.

  13. The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

    Science.gov (United States)

    Jiang, Xiaoliang; Chen, Wei; Liu, Xing; Wang, Zihao; Liu, Yunpeng; Felder, Robin A; Gildea, John J; Jose, Pedro A; Qin, Chuan; Yang, Zhiwei

    2016-01-01

    Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs) is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake.

  14. Development of a Physiologically Based Computational Kidney Model to Describe the Renal Excretion of Hydrophilic Agents in Rats

    Science.gov (United States)

    Niederalt, Christoph; Wendl, Thomas; Kuepfer, Lars; Claassen, Karina; Loosen, Roland; Willmann, Stefan; Lippert, Joerg; Schultze-Mosgau, Marcus; Winkler, Julia; Burghaus, Rolf; Bräutigam, Matthias; Pietsch, Hubertus; Lengsfeld, Philipp

    2013-01-01

    A physiologically based kidney model was developed to analyze the renal excretion and kidney exposure of hydrophilic agents, in particular contrast media, in rats. In order to study the influence of osmolality and viscosity changes, the model mechanistically represents urine concentration by water reabsorption in different segments of kidney tubules and viscosity dependent tubular fluid flow. The model was established using experimental data on the physiological steady state without administration of any contrast media or drugs. These data included the sodium and urea concentration gradient along the cortico-medullary axis, water reabsorption, urine flow, and sodium as well as urea urine concentrations for a normal hydration state. The model was evaluated by predicting the effects of mannitol and contrast media administration and comparing to experimental data on cortico-medullary concentration gradients, urine flow, urine viscosity, hydrostatic tubular pressures and single nephron glomerular filtration rate. Finally the model was used to analyze and compare typical examples of ionic and non-ionic monomeric as well as non-ionic dimeric contrast media with respect to their osmolality and viscosity. With the computational kidney model, urine flow depended mainly on osmolality, while osmolality and viscosity were important determinants for tubular hydrostatic pressure and kidney exposure. The low diuretic effect of dimeric contrast media in combination with their high intrinsic viscosity resulted in a high viscosity within the tubular fluid. In comparison to monomeric contrast media, this led to a higher increase in tubular pressure, to a reduction in glomerular filtration rate and tubular flow and to an increase in kidney exposure. The presented kidney model can be implemented into whole body physiologically based pharmacokinetic models and extended in order to simulate the renal excretion of lipophilic drugs which may also undergo active secretion and reabsorption

  15. 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

  16. Treatment-related changes in urinary excretion of high and low molecular weight proteins in patients with idiopathic membranous nephropathy and renal insufficiency.

    NARCIS (Netherlands)

    Buf-Vereijken, P.W.G. du; Wetzels, J.F.M.

    2006-01-01

    BACKGROUND: In patients with idiopathic membranous nephropathy, an increased urinary excretion of high (IgG) and low [beta(2)-microglobulin (beta(2)M), alpha(1)-microglobulin (alpha(1)M)] molecular weight proteins predicts prognosis and precedes renal insufficiency. We have studied the changes in th

  17. Precipitation of sodium acid urate from electrolyte solutions

    Science.gov (United States)

    Füredi-Milhofer, Helga; Babić-Ivaniĉić, Vesna; Milat, Ognjen; Brown, Walter E.; Gregory, Thomas M.

    1987-07-01

    The precipitation of soduim urate from solutions containing uric acid, soduim hydroxide, hydrochloric acid, sodium chloride and water was investigated at constant pH (7.5±0.1) and temperature (308 K). Precipitates were observed by lights and electron microscopy and characterized by electron and X-ray diffraction. The results are presented in the form of "precipitation" and "chemical potential" diagrams, the latter giving the soduim-to-urate molar ratios of the precipitates. Two types of precipitation boundaries were observed, both of which had indicated soduim-to-urate moral ratios of 1:1. The ion activity product, (Na +)(HU -), associated with boundary I was AP I=(4.8±1.1)×10 -5 and with boundary II was with boundary II was AP II=(6.5±0.4)×10 -4. The supersaturation, S, at boundary II was S=AP II/ Ksp=12.3, in which Ksp is the solubility product of soduim acid urate monohydrate. The latter precipitated as well-formed crystals at supersaturations of 12.3 and above. The ion activity product associated with boundary I is approximately equal to the solubility product of soduim acid urate monohydrate. Small amounts of several morphologically different sodium urate crystals formed in the range of supersaturations (1≤ S≤12.3). Crystals formed in this range may include the monohydrate of sodium acid urate and possibly a higher hydrate. The findings have relevance to pathological renal stone formation and gouty arthritis.

  18. Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins

    DEFF Research Database (Denmark)

    Hsu, Yu-Juei; Dimke, Henrik Anthony; Schoeber, Joost P H

    2010-01-01

    . Androgen deficiency increased the abundance of the renal mRNA and protein of both the luminal transient receptor potential vanilloid-subtype 5 (TRPV5) and intracellular calbindin-D(28K) transporters, which in turn were suppressed by testosterone treatment. There were no significant differences in serum...

  19. Urinary protein excretion pattern and renal expression of megalin and cubilin in nephropathic cystinosis.

    NARCIS (Netherlands)

    Wilmer, M.J.G.; Christensen, E.I.; Heuvel, L.P.W.J. van den; Monnens, L.A.H.; Levtchenko, E.N.

    2008-01-01

    BACKGROUND: Nephropathic cystinosis is the most common cause of inherited renal Fanconi syndrome, caused by mutations in lysosomal cystine carrier cystinosin that result in lysosomal cystine accumulation throughout the body. How defects in cystinosin cause proximal tubular dysfunction is not known.

  20. The diapause program impacts renal excretion and molecular expression of aquaporins in the northern house mosquito, Culex pipiens.

    Science.gov (United States)

    Yang, Liu; Denlinger, David L; Piermarini, Peter M

    2016-12-27

    Adult females of the mosquito Culex pipiens entering diapause increase sugar water ingestion and reduce evaporative water loss, but how these attributes of the diapause program impact activity of the renal excretory system remains unknown. Here we compared the renal excretory capacity of diapausing and non-diapausing females, as well as the molecular expression of aquaporin (AQP) genes that encode channels involved in transporting water and/or small metabolites. Baseline urine excretion rates in diapausing mosquitoes were higher than in those of their non-diapausing counterparts, possibly a consequence of the intense sugar feeding associated with diapause. But, diapausing mosquitoes exhibited a much lower capacity for diuresis than non-diapausing mosquitoes. The suppressed diuretic capacity likely reflects reduced investment in the energetically-expensive post-prandial diuresis, an event not observed in diapausing mosquitoes. The mRNA expression levels of two genes encoding AQPs, Eglp1 and Aqp12L, in diapausing mosquitoes were down-regulated (on day 14) and up-regulated (on both days 3 and 14), respectively, in whole body samples. These changes were not evident in the excretory system (i.e., Malpighian tubules and hindgut), which showed no differential expression of AQPs as a function of diapause. Several AQP mRNAs were, however, differentially expressed in the midgut, ovaries, and abdominal body wall of diapausing mosquitoes, suggesting that AQPs in these tissues may be playing important non-excretory roles that are unique to diapause physiology.

  1. Dose dependency of fermentation and the extent of renal excretion of palatinit (isomalt) in rats with respect to its energy value.

    Science.gov (United States)

    Herfarth, H; Klingebiel, L; Juhr, N C; Grossklaus, R

    1994-09-01

    The impact of dose-dependent caloric salvage by microbial fermentation processes in the lower gut and the extent of renal excretion for the overall energetic availability of the alternative bulk sweetener Palatinit were investigated in rats. To evaluate the extent of dose-dependent fermentation a conventional and a germ-free rat model were used and fecal excretions of Palatinit after intragastric application were compared. Because of the lack of bacterial colonization in the gastrointestinal tract in germ-free rat the difference in fecal excretion of Palatinit between germ-free and conventional rat is mainly due to bacterial fermentation. To determine the amount of renal excretion of Palatinit the urine was collected. The experiments were conducted using different amounts of Palatinit (300 and 1,200 mg/kg body weight = mg/kg b.w.). Fecal excretions of Palatinit and its monomers (sorbitol and mannitol) were measured by high-performance liquid chromatography (HPLC) and for the determination of renal excretions a gas chromatography system was used. After the application of 300 mg/kg b.w. Palatinit only the breakdown product sorbitol could be recovered in the feces of germ-free rats (29% of the applied dose). No intact Palatinit could be found. In contrast, neither Palatinit nor the breakdown products sorbitol or mannitol could be detected in the feces of conventional rats after application of the same dose. After the application of the higher dose only small amounts of intact Palatinit were found in the feces of germ-free rats (average 12%). There was no intact measurable Palatinit in the feces of conventional rats. The fecal excretions of sorbitol and mannitol in the feces of the germ-free rats were 55% and 39%; in conventional rats only 21% sorbitol was excreted. Only traces of Palatinit, sorbitol or mannitol were found in the urine of conventional and germ-free rats after application of the low as well as the high dose. In conclusion, this study clearly shows the

  2. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility...... at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion...

  3. EFFECT OF CASEIN-BASED SEMISYNTHETIC FOOD ON RENAL ACID EXCRETION AND ACID-BASE STATE OF BLOOD IN DOGS

    NARCIS (Netherlands)

    ZIJLSTRA, WG; LANGBROEK, AJM; KRAAN, J; RISPENS, P; NIJMEIJER, A

    1995-01-01

    Urinary acid excretion and blood acid-base stare were determined in dogs fed a casein-based semi-synthetic food (SSF), to which different amounts of salts had been added, in comparison with feeding normal dog food. Net acid excretion (NAE) and inorganic acid excretion (IAE) increased during SSF feed

  4. An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension.

    Science.gov (United States)

    Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal; Schmidlin, Olga; Tanaka, Masae; Morris, R Curtis

    2016-11-01

    It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive control subjects) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: (i) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and (ii) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets.

  5. Influence of insulin on plasma concentration and renal excretion of sodium and potassium in normal, electrolytes depleted and aldosterone treated dogs.

    Science.gov (United States)

    Bak, M; Szczepańska-Sadowska, E; Krzymień, J; Kozłowski, S; Czyzyk, A

    1987-10-01

    Effects of insulin on plasma concentration and renal excretion of sodium and potassium were compared in conscious dogs 1) maintained in water and electrolytes balance (Series 1, 10 dogs), 2) depleted of electrolytes by repeated i.v. loading with 20% mannitol (Series 2, 10 dogs), and 3) aldosterone treated (0.8 micrograms.kg-1.h-1 i.v., Series 3, 10 dogs). In each Series intravenous infusion of insulin at a rate of 0.05 U.kg-1.h-1 elicited transient increase in plasma sodium concentration and prolonged hypokalemia. Repeated loading with mannitol in Series 2 elicited significant elevation of plasma sodium, ADH and aldosterone concentrations, as well as decrease in extracellular fluid volume. Infusion of insulin in this Series elicited smaller decrease in plasma potassium concentration and longer lasting hypernatremia than in dogs in water-electrolytes balance. Aldosterone infusion in Series 3 did not change hypokalemic effect of insulin but attenuated hypernatremia. Infusion of insulin in Series 1 elicited increase of sodium excretion and decrease in potassium excretion. These effects were absent in Series 2 and 3. The results indicate that depletion of electrolytes and blood aldosterone elevation modify the effects of insulin on plasma concentration and renal excretion of sodium and potassium.

  6. 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...

  7. The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps’ activities and urinary excretion of natriuretic peptides

    Directory of Open Access Journals (Sweden)

    Diniz Lúcio Ricardo

    2012-04-01

    Full Text Available Abstract Background In a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAaD reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight. In the present study, we investigated whether atrial natriuretic peptides (ANP and renal ATPases play a role in the SAPAaD- induced antidiuresis in rats. Methods To evaluate the effect of SAPAaD on furosemide-induced diuresis, Wistar rats (250-300 g were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg was given 30 min after rats were orally treated with 50 mg/kg SAPAaD (SAPAaD + Furo or 0.5 ml of 0.9 % NaCl (NaCl + Furo. In the SAPAaD + NaCl group, rats were pretreated with SAPAaD and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h. To investigate the role of ANP and renal Na+ pumps on antidiuretic effects promoted by SAPAaD, rats were given the physiological solution (as above containing SAPAaD (50 mg/kg. After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA and renal cortical activities of Na+- and (Na+,K+-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively. Results It was observed that SAPAaD inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p +-ATPase (from 25.0 ± 5.9 nmol Pi

  8. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Bridget M. Stroup

    2017-01-01

    Full Text Available Background. Skeletal fragility is a complication of phenylketonuria (PKU. A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF. Design. In a crossover design, 8 participants with PKU (16–35 y provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL of AA-MF and GMP-MF and determined bone mineral density (BMD measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p=0.002. Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p=0.012 and magnesium by 30% (p=0.029. Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

  9. Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.

    Science.gov (United States)

    Al-Qusairi, Lama; Basquin, Denis; Roy, Ankita; Stifanelli, Matteo; Rajaram, Renuga Devi; Debonneville, Anne; Nita, Izabela; Maillard, Marc; Loffing, Johannes; Subramanya, Arohan R; Staub, Olivier

    2016-08-01

    The stimulation of postprandial K(+) clearance involves aldosterone-independent and -dependent mechanisms. In this context, serum- and glucocorticoid-induced kinase (SGK)1, a ubiquitously expressed kinase, is one of the primary aldosterone-induced proteins in the aldosterone-sensitive distal nephron. Germline inactivation of SGK1 suggests that this kinase is fundamental for K(+) excretion under conditions of K(+) load, but the specific role of renal SGK1 remains elusive. To avoid compensatory mechanisms that may occur during nephrogenesis, we used inducible, nephron-specific Sgk1(Pax8/LC1) mice to assess the role of renal tubular SGK1 in K(+) regulation. Under a standard diet, these animals exhibited normal K(+) handling. When challenged by a high-K(+) diet, they developed severe hyperkalemia accompanied by a defect in K(+) excretion. Molecular analysis revealed reduced neural precursor cell expressed developmentally downregulated protein (NEDD)4-2 phosphorylation and total expression. γ-Epithelial Na(+) channel (ENaC) expression and α/γENaC proteolytic processing were also decreased in mutant mice. Moreover, with no lysine kinase (WNK)1, which displayed in control mice punctuate staining in the distal convoluted tubule and diffuse distribution in the connecting tubule/cortical colleting duct, was diffused in the distal convoluted tubule and less expressed in the connecting tubule/collecting duct of Sgk(Pax8/LC1) mice. Moreover, Ste20-related proline/alanine-rich kinase phosphorylation, and Na(+)-Cl(-) cotransporter phosphorylation/apical localization were reduced in mutant mice. Consistent with the altered WNK1 expression, increased renal outer medullary K(+) channel apical localization was observed. In conclusion, our data suggest that renal tubular SGK1 is important in the regulation of K(+) excretion via the control of NEDD4-2, WNK1, and ENaC.

  10. Negative correlation between serum uric acid and kidney URAT1 mRNA expression caused by resveratrol in rats.

    Science.gov (United States)

    Lee, Cheng-Tse; Chang, Li-Ching; Liu, Ching-Wen; Wu, Pei-Fung

    2017-10-01

    This study established a hyperuricemic rat model to elucidate the effect of resveratrol on the transport of UA in the kidney. Hyperuricemia was induced in rats through daily oral gavage of a potassium oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol significantly reduced the serum UA levels but not creatinine, c-creative protein, alanine aminotransferase, or aspartate aminotransferase levels in these rats. Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in the rats treated with allopurinol than in those with no treatment. Therefore, allopurinol not only inhibited UA production but also mediated renal URAT1 and OAT1 expression. The correlation analysis revealed that UA levels correlated negatively with renal IL-6 mRNA expression in rats treated with allopurinol. Moreover, URAT1 showed strong immunoreactivity in the distal convoluted tubule of rats treated with allopurinol or resveratrol and in hyperuricemic treated with allopurinol. Finally, in the rats treated with resveratrol, UA levels correlated negatively with renal URAT1 mRNA expression; thus, resveratrol reduced URAT1 mRNA expression under high UA levels, thereby reducing UA reabsorption in renal cells. Resveratrol contributes to URAT1 expression, which is potentially useful in therapeutic strategies aimed at treating hyperuricemia. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Homozygous SLC2A9 mutations cause severe renal hypouricemia.

    Science.gov (United States)

    Dinour, Dganit; Gray, Nicola K; Campbell, Susan; Shu, Xinhua; Sawyer, Lindsay; Richardson, William; Rechavi, Gideon; Amariglio, Ninette; Ganon, Liat; Sela, Ben-Ami; Bahat, Hilla; Goldman, Michael; Weissgarten, Joshua; Millar, Michael R; Wright, Alan F; Holtzman, Eliezer J

    2010-01-01

    Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 +/- 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.

  12. Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals

    Science.gov (United States)

    Pieterse, Elmar; Jeremic, Ivica; Czegley, Christine; Weidner, Daniela; Biermann, Mona H.C.; Veissi, Susan; Maueröder, Christian; Schauer, Christine; Bilyy, Rostyslav; Dumych, Tetiana; Hoffmann, Markus; Munoz, Luis E.; Bengtsson, Anders A.; Schett, Georg; van der Vlag, Johan; Herrmann, Martin

    2016-01-01

    Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host. Here, we report that complement proteins and fetuins facilitate the continuous clearance by blood-borne phagocytes and resident macrophages of small urate microaggregates (UMA; <1 μm in size) that initially form in hyperuricemic blood. If this clearance fails, UMA exhibit bipolar growth to form typical full-sized nsMSU with a size up to 100 μm. In contrast to UMA, nsMSU stimulated neutrophils to release NETs. Under conditions of flow, nsMSU and NETs formed densely packed DNase I-resistant tophus-like structures with a high obstructive potential, highlighting the importance of an adequate and rapid removal of UMA from the circulation. Under pathological conditions, intravascularly formed nsMSU may hold the key to the incompletely understood association between NET-driven cardiovascular disease and hyperuricemia. PMID:27917897

  13. [Hyperuricemia and renal risk].

    Science.gov (United States)

    Viazzi, Francesca; Bonino, Barbara; Ratto, Elena; Desideri, Giovambattista; Pontremoli, Roberto

    2015-01-01

    Recent studies have revealed an association between elevated levels of uric acid and conditions correlated to chronic kidney diseases such as hypertension, cardiovascular and cerebral disease, insulin resistance. Several pathogenetic mechanisms at cellular and tissue levels could justify a direct correlation between serum uric acid levels and renal damage. Growing evidence indicating a correlation between urate lowering therapy and renal morbidity could encourage the use of urate lowering therapy in primary or secondary prevention in chronic kidney disease.

  14. An orally active adenosine A1 receptor antagonist, FK838, increases renal excretion and maintains glomerular filtration rate in furosemide-resistant rats

    Science.gov (United States)

    Schnackenberg, Christine G; Merz, Emily; Brooks, David P

    2003-01-01

    Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate.We tested the hypothesis that the selective adenosine A1 receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance.In normal male Sprague – Dawley rats, FK838 dose-dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide-resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide-resistant rats.This study shows that the adenosine A1 receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide-resistant rats. Adenosine A1 receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic-resistant patients. PMID:12922924

  15. Pathology of spontaneous tubular proteinuria evaluated by renal scintigraphy {sup 99m}-Tc-dimercaptosuccinic acid (DMSA). Second report. Evaluation of urinary excretion and urinary bladder uptake images

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takeshi; Hosaki, Tomoko; Shimizu, Mariko [Fussa Hospital, Tokyo (Japan)] [and others

    2000-03-01

    The significance of DMSA uptake in the urinary bladder and %uptake in renal scintigrams with {sup 99m}Tc-DMSA in spontaneous tubular proteinuria was reassessed. The subjects were 10 patients in whom DMSA uptake in the urinary bladder could be clearly evaluated among 15 cases that were tentatively diagnosed as having spontaneous tubular proteinuria and in which renal scintigraphy was performed with DMSA. All of the patients were male children and their mean age was 9 years 11 months. No morphological abnormalities in the kidneys could be detected in any of the cases, and %uptake of DMSA was very low. Urinary excretion and uptake of the nuclide in the urinary bladder was significantly increased. In view of the pharmacokinetics of DMSA, the patients' disease appeared to be complicated by failure of the proximal tubule epithelial cells to resorb low-molecular-weight proteins, and the failure of active transport on the vascular lumen side of the cells. As a result, urinary excretion was increased and marked uptake in the urinary bladder was induced. Accordingly, when %uptake of DMSA cannot be measured, it is necessary to determine the extent of uptake in the urinary bladder. When images showing abnormal uptake are obtained, the possibility of diseases associated with functional failure at the proximal tubular level, such as spontaneous tubular proteinuria, is quite high. (K.H.)

  16. Urinary magnesium excretion and risk of hypertension. The prevention of renal and vascular end-stage disease study

    NARCIS (Netherlands)

    Joosten, M.M.; Gansevoort, R.T.; Mukamal, K.J.; Kootstra-Ros, J.E.; Feskens, E.J.M.; Geleijnse, J.M.; Navis, G.; Bakker, S.J.L.

    2013-01-01

    Observational studies on dietary or circulating magnesium and risk of hypertension have reported weak-to-modest inverse associations, but have lacked measures of actual dietary uptake. Urinary magnesium excretion, an indicator of intestinal magnesium absorption, may provide a better insight in this

  17. Urinary Magnesium Excretion and Risk of Hypertension The Prevention of Renal and Vascular End-Stage Disease Study

    NARCIS (Netherlands)

    Joosten, Michel M.; Gansevoort, Ron T.; Mukamal, Kenneth J.; Kootstra-Ros, J.E.; Feskens, Edith J. M.; Geleijnse, Johanna M.; Navis, Gerjan; Bakker, Stephan J. L.

    2013-01-01

    Observational studies on dietary or circulating magnesium and risk of hypertension have reported weak-to-modest inverse associations, but have lacked measures of actual dietary uptake. Urinary magnesium excretion, an indicator of intestinal magnesium absorption, may provide a better insight in this

  18. Urinary Potassium Excretion and Risk of Developing Hypertension The Prevention of Renal and Vascular End-Stage Disease Study

    NARCIS (Netherlands)

    Kieneker, Lyanne M.; Gansevoort, Ron T.; Mukamal, Kenneth J.; de Boer, Rudolf A.; Navis, Gerjan; Bakker, Stephan J. L.; Joosten, Michel M.

    2014-01-01

    Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of t

  19. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

    Science.gov (United States)

    Flynn, F. V.; Lapsley, M.; Sansom, P. A.; Cohen, S. L.

    1992-01-01

    AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive

  20. [Two elderly case reports of renal excretion type drug poisoning caused by dehydration that was due to poor eating in home care].

    Science.gov (United States)

    Ibata, Takeshi; Hinokiyama, Hiromi; Nakashita, Chisako; Mito, Saori; Doi, Seiko; Shiki, Satomi; Hata, Akiko; Sato, Miyuki; Komuro, Ryutaro; Iijima, Hohei

    2010-12-01

    The elderly patients are susceptible to acute renal failure due to dehydration or infection. Therefore, the drug should be administered with caution. We report two cases of acute renal failure from dehydration that led to a subsequent drug poisoning. Case 1: An 85-year-old woman with a history of colorectal cancer surgery was admitted to our emergency department for appetite loss and weakness. Because she was given a normal amount of drugs under the condition of poor oral intake, she was hospitalized by digitalism. Case 2: A 72-year-old woman was admitted to our emergency department for disturbance of consciousness and appetite loss. The medication given by a staff in geriatric health services facility appeared to have caused a pilsicainide poisoning. As the elderly patients were given a normal amount of drugs under the poor oral intake condition, blood levels of renal excretion type drug had increased in both cases. Medication management for the elderly should be comprehensively considered the background of the individual.

  1. Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study

    DEFF Research Database (Denmark)

    Søltoft Larsen, Kasper; Pottegård, Anton; Lindegaard, Hanne M

    2016-01-01

    , laboratory values and in- and outpatient contacts. RESULTS: No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28). No significant effect was seen in any subgroup defined by age, gender, renal function......BACKGROUND: Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known. OBJECTIVES......: To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol. METHODS: We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular...

  2. Impact of urate level on cardiovascular risk in allopurinol treated patients. A nested case control study

    DEFF Research Database (Denmark)

    Larsen, Kasper Søltoft; Pottegård, Anton; Lindegaard, H. M.

    2015-01-01

    odds ratio for cardiovascular event between cases and controls was 1.01 (95% confidence interval 0.80 - 1.29). No significant effect was seen in any subgroup when stratifying by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used......Background: Gout gives rise to increased risk of adverse cardiovascular outcomes. Gout attacks can be effectively prevented with urate lowering drugs such as allopurinol, and allopurinol further potentially reduces the cardiovascular risk. Whether treatment to a target level of uric acid...... is required to reduce cardiovascular risk is not known. Objectives: We sought to investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case control study nested within long-term users of allopurinol. Methods: We identified all long-term users of allopurinol...

  3. Role of gp91phox -containing NADPH oxidase in mediating the effect of K restriction on ROMK channels and renal K excretion.

    Science.gov (United States)

    Babilonia, Elisa; Lin, Daohong; Zhang, Yan; Wei, Yuan; Yue, Peng; Wang, Wen-Hui

    2007-07-01

    Previous study has demonstrated that superoxide and the related products are involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity in the cortical collecting duct (CCD). This study investigated the role of gp91(phox)-containing NADPH oxidase (NOXII) in mediating the effect of low K intake on renal K excretion and ROMK channel activity in gp91(-/-) mice. K depletion increased superoxide levels, phosphorylation of c-Jun, expression of c-Src, and tyrosine phosphorylation of ROMK in renal cortex and outer medulla in wild-type (WT) mice. In contrast, tempol treatment in WT mice abolished whereas deletion of gp91 significantly attenuated the effect of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK. Patch-clamp experiments demonstrated that low K intake decreased mean product of channel number (N) and open probability (P) (NP(o)) of ROMK channels from 1.1 to 0.4 in the CCD. However, the effect of low K intake on ROMK channel activity was significantly attenuated in the CCD from gp91(-/-) mice and completely abolished by tempol treatment. Immunocytochemical staining also was used to examine the ROMK distribution in WT, gp91(-/-), and WT mice with tempol treatment in response to K restriction. K restriction decreased apical staining of ROMK in WT mice. In contrast, a sharp apical ROMK staining was observed in the tempol-treated WT or gp91(-/-) mice. Metabolic cage study further showed that urinary K loss is significantly higher in gp91(-/-) mice than in WT mice. It is concluded that superoxide anions play a key role in suppressing K secretion during K restriction and that NOXII is involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity.

  4. 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...

  5. Disease: H00948 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available zed by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells, and high urina...ry urate excretion. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apic

  6. Aquaporin-2 excretion and renal function during the 1st week of life in preterm newborn infants.

    NARCIS (Netherlands)

    Iacobelli, S.; Addabbo, F.; Bonsante, F.; Procino, G.; Tamma, G.; Acito, A.; Esposito, L.; Svelto, M.; Valenti, G.

    2006-01-01

    In many preterm infants, a characteristic pattern of fluid and electrolyte homeostasis occurs during the 1st week of life, consisting of three phases: prediuretic, diuretic, and postdiuretic. In this study, we evaluated the possible role of aquaporin-2 (AQP2) in renal concentrating ability and corre

  7. SLC2A9 is a high-capacity urate transporter in humans.

    Directory of Open Access Journals (Sweden)

    Mark J Caulfield

    2008-10-01

    Full Text Available BACKGROUND: Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man. METHODS AND FINDINGS: We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 microM. Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 microM. Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio

  8. Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

    Directory of Open Access Journals (Sweden)

    J.V.M. Franquini

    2009-02-01

    Full Text Available Obstructive apnea (OA can exert significant effects on renal sympathetic nerve activity (RSNA and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9, which were compared to sham (S; N = 9 rats. Mean arterial pressure (MAP and heart rate (HR were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg or HR (S: 340 ± 12 vs D: 368 ± 11 bpm. An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01. The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9% during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

  9. Plasma Urate and Parkinson's Disease in Women

    OpenAIRE

    O'Reilly, Éilis J.; Gao, Xiang; Weisskopf, Marc G.; Chen, Honglei; Schwarzschild, Michael A.; Spiegelman, Donna; Ascherio, Alberto

    2010-01-01

    Plasma urate has been consistently associated with a lower risk of Parkinson's disease in men, but it is less clear if this relation exists in women. Between 1990 and 2004, the authors conducted a nested case-control study among participants of the female-only Nurses’ Health Study. In controls (n = 504), plasma urate was positively associated with age, body mass index, alcohol consumption, hypertension, and use of diuretics and was inversely associated with physical activity and postmenopausa...

  10. Relationship between urinary albumin excretion rate and renal histology in non-insulin-dependent diabetes mellitus: with reference to the clinical significance of microalbuminuria.

    Science.gov (United States)

    Inomata, S; Nakamoto, Y; Inoue, M; Itoh, M; Ohsawa, Y; Masamune, O

    1989-01-01

    The present study demonstrates the relationship between urinary albumin excretion rate (AER) and renal structural changes in patients with non-insulin-dependent diabetes mellitus (NIDDM) without clinical proteinuria. Resting AER in 30 control subjects and 67 NIDDM patients were 10.4 +/- 4.8 (mean +/- SD) micrograms/min (range 4.3-21.1 micrograms/min) and 26.4 +/- 32.3 micrograms/min (range 0.4-155 micrograms/min), respectively. Persistent normoalbuminuria (less than 20 micrograms/min) and microalbuminuria (20-200 micrograms/min) were found in 43 (Group A) and 24 (Group B) diabetics. There were significant differences in age, diabetes duration, and frequency of retinopathy (background and proliferative) as well as that of proliferative retinopathy between Groups A and B, but not in the other clinical parameters such as body mass index, HbA1, Ccr, or systolic and diastolic blood pressure (SBP, DBP). When compared with 11 normoalbuminuric patients of similar age and equal diabetes duration to those in Group B, the sole difference in clinical parameters was the existence of proliferative retinopathy in Group B. Renal structural changes were investigated by light microscopy in 14 people in Group A and 13 people in Group B, and additionally in 5 NIDDM patients with both macroalbuminuria (greater than or equal to 200 micrograms/min) and normal or nearly normal renal function (Group C). The diffuse glomerular lesion (Gellman's classification) was grade I or II in A, II or III in B, and III in C.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Excreção renal de fósforo em cães nefropatas sob estimulação dopaminérgica Renal excretion of phosphorus in nephropathy dogs under dopaminergic stimulation

    Directory of Open Access Journals (Sweden)

    Alexandre Martini de Brum

    2010-06-01

    Full Text Available A dopamina possui um amplo espectro de ação no sistema urinário. Aumento da taxa de filtração glomerular, do fluxo sanguíneo renal e da excreção fracionada de sódio e fósforo é um efeito renal esperado em indivíduos normais. Este estudo foi realizado com o propósito de testar a hipótese de que a dopamina é capaz de aumentar a excreção fracionada de fósforo em cães nefropatas. Cinco cães sadios e quatro cães nefropatas, com doença predominantemente túbulo-intersticial, foram submetidos à infusão de solução controle (NaCl 0,9% e solução de dopamina em duas taxas de infusão diferentes (1µg kg-1 min-1 e 3µg kg-1 min-1, sendo realizadas avaliações antes, durante e 30 minutos após a infusão. Os cães sadios apresentaram aumento significativo (P≤0,05 na excreção fracionada e excreção renal de fósforo durante a infusão de 3µg kg-1 min-1, porém a concentração sérica permaneceu sem alterações durante o tratamento. Já os cães nefropatas apresentaram aumento significativo (P≤0,05 na excreção fracionada e excreção renal de fósforo, tanto na dose de 1µg kg-1 min-1, como na de 3µg kg-1 min-1. Além disso, após a infusão de 1µg kg-1min-1, a concentração sérica de fósforo apresentou redução significativa. Os resultados são indicativos de que a dopamina nas doses de 1µg kg-1 min-1 e 3µg kg-1 min-1 podem ser incluídas na terapia de cães nefropatas para melhorar a homeostase de fosfato.The dopamine has a wide spectrum of action on the urinary system. Increases in glomerular filtration rate, renal blood flow, sodium and phosphate fractioned excretion are renal effects expected in healthy people. Thus, this study was conducted in order to test the hypothesis that the dopamine is efficient to increase the fractioned excretion of phosphorus in nephropathic dogs. Five healthy dogs and four dogs nephropathic, predominantly with tubule-interstitial illness were submitted to a solution control

  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

    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

  13. Bright Star Astrometry with URAT

    CERN Document Server

    Zacharias, Norbert

    2015-01-01

    The U.S. Naval Observatory Robotic Astrometric Telescope (URAT) is observing the northern sky since April 2012 for an astrometric survey. Multiple overlaps per year are performed in a single bandpass (680$-$750 nm) using the "redlens" 20 cm aperture astrograph and a mosaic of large CCDs. Besides the regular, deep survey to magnitude 18.5, short exposures with an objective grating are taken to access stars as bright as 3rd magnitude. A brief overview of the program, observing and reductions is given. Positions on the 8 to 20 mas level are obtained of 66,202 Hipparcos stars at current epochs. These are compared to the Hipparcos Catalog to investigate its accuracy. About 20\\% of the observed Hipparcos stars are found to have inconsitent positions with the Hipparcos Catalog prediction on the 3 sigma level or over (about 75 mas or more discrepant position offsets). Some stars are now seen at an arcsec (or 25 sigma) off their Hipparcos Catalog predicted position.

  14. BRIGHT STAR ASTROMETRY WITH URAT

    Directory of Open Access Journals (Sweden)

    N. Zacharias

    2015-01-01

    Full Text Available El Telescopio Rob ́otico Astrom ́etrico del Observatorio Naval de los Estados Unidos de Am ́erica (URAT est ́a observando el cielo del norte desde Abril 2012 para un sondeo astrom ́etrico. M ́ultiples traslapos por a ̃no se realizan en un ́unico filtro (680 − 750 nm usando la “lente-roja” de un astr ́ografo de 20 cm y un mosaico de grandes CCDs. Adem ́as del sondeo regular y profundo hasta magnitud 18.5, se hacen expos iciones cortas con una rejilla en el objetivo para tener acceso a estrellas tan brillantes como de ter cera magnitud. En este trabajo se describe de forma sucinta el programa, las observaciones y las reduccio nes. Se obtienen posiciones a nivel de 8 a 20 msa para 66,202 estrellas Hipparcos en la ́epoca actual. Estas son comparadas con Hipparcos para investigar su incertidumbre. Alrededor de un 20% de las estrellas Hipparcos obser vadas tienen posiciones inconsistentes con las predichas por el Cat ́alogo Hipparcos a un nivel 3 sigma o s uperior (alrededor de 75 msa o m ́as de discrepancia en posici ́on. Algunas estrellas ahora se observan a un segundo de arco (o 25 sigma desplazadas de la posici ́on predicha por el Cat ́alogo Hipparcos.

  15. Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Kasper Søltoft Larsen

    Full Text Available Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known.To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol.We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts.No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28. No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day.We were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.

  16. Uric Acid Excretion Predicts Increased Blood Pressure Among American Adolescents of African Descent.

    Science.gov (United States)

    Mrug, Sylvie; Mrug, Michal; Morris, Anjana Madan; Reynolds, Nina; Patel, Anita; Hill, Danielle C; Feig, Daniel I

    2017-04-01

    Hyperuricemia predicts the incidence of hypertension in adults and its treatment has blood pressure (BP)-lowering effects in adolescents. To date, no studies have examined the predictive usage of hyperuricemia or urinary uric acid excretion on BP changes in adolescents. Mechanistic models suggest that uric acid impairs both endothelial function and vascular compliance, which would potentially exacerbate a myriad of hypertensive mechanisms, yet little is known about interaction of uric acid and other hypertension risk factors. The primary study was aimed at the effects of stress on BP in adolescents. A community sample of 84 low-income, urban adolescents (50% male, 95% African American, mean age = 13.36 ± 1 years) was recruited from public schools. Youth completed a 12-hour (overnight) urine collection at home and their BP was measured during rest and in response to acute psychosocial stress. Seventy-six of the adolescents participated in a follow-up visit at 1.5 years when their resting BP was reassessed. In this substudy, we assessed the relationship of renal urate excretion and BP reactivity. After adjusting for resting BP levels at baseline and other covariates, higher levels of uric acid excretion predicted greater BP reactivity to acute psychosocial stress and higher resting BP at 18 months. Urinary excretion of uric acid can serve as an alternative, noninvasive measure of serum uric acid levels that are predictive of BP changes. As hyperuricemia-associated hypertension is treatable, urban adolescents may benefit from routine screening for hyperuricemia or high uric acid excretion. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  17. Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

    Directory of Open Access Journals (Sweden)

    Yun-rui Zhang

    2015-09-01

    Full Text Available Objectives: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd and biomarkers of renal dysfunction. Methods: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre, β2-microglobulin (β2-MG, α1-microglobulin (α1-MG, metallothionein (MT, retinol binding protein (RBP, albumin (AB, N-acetyl-β-D-glucosaminidase (NAG, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (GGT and kidney injury molecule-1 (KIM-1. Spearman’s rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model were used to model the dose-response relationships between U-Cd and nine urine markers. Results: Spearman’s rank correlation showed that NAG, ALP, RBP, β2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R2 of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. Conclusions: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

  18. Chemical Characterization of Urate Hydroperoxide, A Pro-oxidant Intermediate Generated by Urate Oxidation in Inflammatory and Photoinduced Processes.

    Science.gov (United States)

    Patrício, Eliziane S; Prado, Fernanda M; da Silva, Railmara P; Carvalho, Larissa A C; Prates, Marcus V C; Dadamos, Tony; Bertotti, Mauro; Di Mascio, Paolo; Kettle, Anthony J; Meotti, Flavia C

    2015-08-17

    Urate hydroperoxide is a strong oxidant generated by the combination of urate free radical and superoxide. The formation of urate hydroperoxide as an intermediate in urate oxidation is potentially responsible for the pro-oxidant effects of urate in inflammatory disorders, protein degradation, and food decomposition. To understand the molecular mechanisms that sustain the harmful effects of urate in inflammatory and oxidative stress related conditions, we report a detailed structural characterization and reactivity of urate hydroperoxide toward biomolecules. Urate hydroperoxide was synthesized by photo-oxidation and by a myeloperoxidase/hydrogen peroxide/superoxide system. Multiple reaction monitoring (MRM) and MS(3) ion fragmentation revealed that urate hydroperoxide from both sources has the same chemical structure. Urate hydroperoxide has a maximum absorption at 308 nm, ε308nm = 6.54 ± 0.38 × 10(3) M(-1) cm(-1). This peroxide decays spontaneously with a rate constant of k = 2.80 ± 0.18 × 10(-4) s(-1) and a half-life of 41 min at 22 °C. Urate hydroperoxide undergoes electrochemical reduction at potential values less negative than -0.5 V (versus Ag/AgCl). When incubated with taurine, histidine, tryptophan, lysine, methionine, cysteine, or glutathione, urate hydroperoxide reacted only with methionine, cysteine, and glutathione. The oxidation of these molecules occurred by a two-electron mechanism, generating the alcohol, hydroxyisourate. No adduct between cysteine or glutathione and urate hydroperoxide was detected. The second-order rate constant for the oxidation of glutathione by urate hydroperoxide was 13.7 ± 0.8 M(-1) s(-1). In conclusion, the oxidation of sulfur-containing biomolecules by urate hydroperoxide is likely to be a mechanism by which the pro-oxidant and damaging effects of urate are mediated in inflammatory and photo-oxidizing processes.

  19. 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 ...

  20. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers

    Directory of Open Access Journals (Sweden)

    Gillen M

    2016-11-01

    Full Text Available Michael Gillen,1 Shakti Valdez,2 Dongmei Zhou,2 Bradley Kerr,2 Caroline A Lee,2 Zancong Shen2 1AstraZeneca LP, Gaithersburg, MD, 2Ardea Biosciences, Inc., San Diego, CA, USA Introduction: Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI in patients who have not achieved target serum uric acid (sUA levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods: Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12 or mild (eCrCl 60–89 mL/min; N=8, moderate (eCrCl 30–59 mL/min; N=16, or severe (eCrCl <30 mL/min; N=6 renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24 or 400 mg (N=18. Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Results: Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma Cmax was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Conclusion: Lesinurad exposure increased with decreasing renal function; however, the

  1. Plasma urate and Parkinson's disease in women.

    Science.gov (United States)

    O'Reilly, Eilis J; Gao, Xiang; Weisskopf, Marc G; Chen, Honglei; Schwarzschild, Michael A; Spiegelman, Donna; Ascherio, Alberto

    2010-09-15

    Plasma urate has been consistently associated with a lower risk of Parkinson's disease in men, but it is less clear if this relation exists in women. Between 1990 and 2004, the authors conducted a nested case-control study among participants of the female-only Nurses' Health Study. In controls (n = 504), plasma urate was positively associated with age, body mass index, alcohol consumption, hypertension, and use of diuretics and was inversely associated with physical activity and postmenopausal hormone use, as expected. Mean urate levels were 5.04 mg/dL for cases (n = 101) and 4.86 mg/dL for controls (P = 0.17). The age-, smoking-, and caffeine-adjusted rate ratio comparing women in the highest (≥5.8 mg/dL) with those in the lowest (body mass index, physical activity, history of hypertension, and postmenopausal hormone use did not change the results. Unlike in men, these findings do not support the hypothesis that urate is strongly associated with lower rates of Parkinson's disease among women.

  2. Is it cerebral or renal salt wasting?

    Science.gov (United States)

    Maesaka, John K; Imbriano, Louis J; Ali, Nicole M; Ilamathi, Ekambaram

    2009-11-01

    Cerebral salt-wasting (CSW), or renal salt-wasting (RSW), has evolved from a misrepresentation of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) to acceptance as a distinct entity. Challenges still confront us as we attempt to differentiate RSW from SIADH, ascertain the prevalence of RSW, and address reports of RSW occurring without cerebral disease. RSW is redefined as 'extracellular volume depletion due to a renal sodium transport abnormality with or without high urinary sodium concentration, presence of hyponatremia or cerebral disease with normal adrenal and thyroid function.' Our inability to differentiate RSW from SIADH lies in the clinical and laboratory similarities between the two syndromes and the difficulty of accurate assessment of extracellular volume. Radioisotopic determinations of extracellular volume in neurosurgical patients reveal renal that RSW is more common than SIADH. We review the persistence of hypouricemia and increased fractional excretion of urate in RSW as compared to correction of both in SIADH, the appropriateness of ADH secretion in RSW, and the importance of differentiating renal RSW from SIADH because of disparate treatment goals: fluid repletion in RSW and fluid restriction in SIADH. Patients with RSW are being incorrectly treated by fluid restriction, with clinical consequences. We conclude that RSW is common and occurs without cerebral disease, and propose changing CSW to RSW.

  3. The effects of URAT1/SLC22A12 nonfunctional variants,R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression

    Science.gov (United States)

    Sakiyama, Masayuki; Matsuo, Hirotaka; Shimizu, Seiko; Nakashima, Hiroshi; Nakamura, Takahiro; Nakayama, Akiyoshi; Higashino, Toshihide; Naito, Mariko; Suma, Shino; Hishida, Asahi; Satoh, Takahiro; Sakurai, Yutaka; Takada, Tappei; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-01-01

    Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10−46). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10−19; risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 × 10−12). PMID:26821810

  4. Association analysis of the beta-3 adrenergic receptor Trp64Arg (rs4994) polymorphism with urate and gout.

    Science.gov (United States)

    Fatima, Tahzeeb; Altaf, Sara; Phipps-Green, Amanda; Topless, Ruth; Flynn, Tanya J; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2016-02-01

    The Arg64 allele of variant rs4994 (Trp64Arg) in the β3-adrenergic receptor gene has been associated with increased serum urate and risk of gout. Our objective was to investigate the relationship of rs4994 with serum urate and gout in New Zealand European, Māori and Pacific subjects. A total of 1730 clinically ascertained gout cases and 2145 controls were genotyped for rs4994 by Taqman(®). Māori and Pacific subjects were subdivided into Eastern Polynesian (EP) and Western Polynesian (WP) sample sets. Publicly available genotype data from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study were utilized for serum urate association analysis. Multivariate logistic and linear regression adjusted for potential confounders was carried out using R version 2.15.2. No significant association of the minor Arg64 (G) allele of rs4994 with gout was found in the combined Polynesian cohorts (OR = 0.98, P = 0.88), although there was evidence, after adjustment for renal disease, for association in both the WP (OR = 0.53, P = 0.03) and the lower Polynesian ancestry EP sample sets (OR = 1.86, P = 0.05). There was no evidence for association with gout in the European sample set (OR = 1.11, P = 0.57). However, the Arg64 allele was positively associated with urate in the WP data set (β = 0.036, P = 0.004, P Corrected = 0.032). Association of the Arg64 variant with increased urate in the WP sample set was consistent with the previous literature, although the protective effect of this variant with gout in WP was inconsistent. This association provides an etiological link between metabolic syndrome components and urate homeostasis.

  5. The beneficial effects of dapagliflozin on the course of experimental urate nephrolithiasis

    Directory of Open Access Journals (Sweden)

    V. Yu. Perfil’ev

    2017-01-01

    Full Text Available Aim of the study. Rate dapagliflozin effective in the prevention and treatment of experimental urate nephropathy.Мaterials and methods. The study was conducted on 30 male rats Wistar stock weighing 220–310 g. For the formation of urate nephropathy in rats using reproduced earlier classic model inhibiting uricase, causing the development of hyperuricemia in rodents. The animal was determined daily urine content MC, total proteins, creatinine, and enzyme activity of renal dysfunction markers LDH, gamma-glutamyl and N-acetyl-β-D-glucosaminidase. After the experiment the rat blood obtained after decapitation determined content MC, creatinine, catalase, glutathione peroxidase, superoxide dismutase, reduced glutathione, thiobarbiturate-reactive products, total antioxidant activity and a common pro-oxidant activity. In the kidneys of rats was determined by the same parameters of free radical oxidation.Results. It was found that prolonged use of dapagliflozin in the prophylactic and therapeutic regimes, despite a decline in urinary pH, significantly improves the condition of animals with experimental urate nephrolithiasis, as evidenced by a significant decrease in the level of uric acid in blood plasma and urine of rats, a decrease in LDH activity in urine and inhibition process is free -radical oxidation.Сonclusion. Prolonged use of dapagliflozin in the prophylactic and therapeutic regimes, despite a decline urine pH, improved the urate nephrolithiasis, as evidenced by a significant decrease in the level of uric acid in blood plasma and urine of rats, decreased activity of LDH in urine and inhibition of the process of free-radical oxidation. 

  6. URAT: astrometric requirements and design history

    CERN Document Server

    Zacharias, N; Rakich, A; Epps, H

    2006-01-01

    The U.S. Naval Observatory Robotic Astrometric Telescope (URAT) project aims at a highly accurate (5 mas), ground-based, all-sky survey. Requirements are presented for the optics and telescope for this 0.85 m aperture, 4.5 degree diameter field-of-view, specialized instrument, which are close to the capability of the industry. The history of the design process is presented as well as astrometric performance evaluations of the toleranced, optical design, with expected wavefront errors included.

  7. URAT: astrometric requirements and design history

    Science.gov (United States)

    Zacharias, Norbert; Laux, Uwe; Rakich, Andrew; Epps, Harland

    2006-06-01

    The U.S. Naval Observatory Robotic Astrometric Telescope (URAT) project aims at a highly accurate (5 mas), ground-based, all-sky survey. Requirements are presented for the optics and telescope for this 0.85 m aperture, 4.5 degree diameter field-of-view, specialized instrument, which are close to the capability of the industry. The history of the design process is presented as well as astrometric performance evaluations of the toleranced, optical design, with expected wavefront errors included.

  8. Effect of urate on the lactoperoxidase catalyzed oxidation of adrenaline.

    Science.gov (United States)

    Løvstad, Rolf A

    2004-12-01

    Lactoperoxidase is an iron containing enzyme, which is an essential component of the defense system of mammalian secretary fluids. The enzyme readily oxidizes adrenaline and other catecholamines to coloured aminochrome products. A Km-value of 1.21 mM and a catalytic constant (k = Vmax/[Enz]) of 15.5 x 10(3) min(-1) characterized the reaction between lactoperoxidase and adrenaline at pH 7.4. Urate was found to activate the enzyme catalyzed oxidation of adrenaline in a competitive manner, the effect decreasing with increasing adrenaline concentration. Lactoperoxidase was able to catalyze the oxidation of urate. However, urate was a much poorer substrate than adrenaline, and it seems unlikely that urate activates by functioning as a free, redox cycling intermediate between enzyme and adrenaline. The activation mechanism probably involves an urate-lactoperoxidase complex.

  9. Effect of casein-based semi-synthetic food on renal acid excretion and acid-base state of blood in dogs.

    Science.gov (United States)

    Zijlstra, W G; Langbroek, A J; Kraan, J; Rispens, P; Nijmeijer, A

    1995-01-01

    Urinary acid excretion and blood acid-base state were determined in dogs fed a casein-based semi-synthetic food (SSF), to which different amounts of salts had been added, in comparison with feeding normal dog food. Net acid excretion (NAE) and inorganic acid excretion (IAE) increased during SSF feeding. IAE was higher than the acid load calculated from the sulphur and phosphorus content of the casein. This higher IAE appeared to be due to the presence of calcium and magnesium phosphate in the diet, because calcium and magnesium may be in part precipitated as carbonate, leaving phosphate to be absorbed as phosphoric acid. Acid excretion decreased by addition of CaO. When no neutral Na+ and K+ salts were added, the increase in NAE was accompanied by a metabolic acidosis. K+ was more effective in attenuating the acidosis than Na+. On the basis of these findings a diet can be made which imposes a known acid load, and provides stable baseline values. Hence, any additions that influence the acid-base balance can be properly studied. The data obtained in these and future studies utilising this diet may be of help in optimising the composition of nutrient solutions to be used in the care of critically ill patients.

  10. [Urinary electrolyte excretion in autosomal dominant polycystic kidney].

    Science.gov (United States)

    Todorov, V; Iordanova, P; Penkova, S

    1991-01-01

    In 33 patients with autosomal dominant renal polycystosis the urine excretion of the electrolytes sodium and potassium was examined and analyzed in relation to the renal function and the arterial pressure. The clearances, the urine ratio and the excreted fractions of both electrolytes were calculated. It was established that by normal renal function and without arterial hypertension there were no significant differences in the parameters studied between the patients and the healthy controls. In the patients with arterial hypertension and preserved renal function the sodium clearance and urine excretion were lower, but the differences with the normotensive patients were not statistically significant. In the patients with chronic renal failure (when diuretic was applied) higher mean values of the excreted fractions of sodium and potassium were established. The results support the thesis that hypertension in renal polycystosis is of volumetric character.

  11. Changes in urinary potassium excretion in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Yuichiro Ueda

    2016-06-01

    Conclusion: This study demonstrated that urinary potassium excretion decreased with reductions in renal function. Furthermore, urinary potassium excretion was mainly affected by urinary sodium excretion and estimated glomerular filtration rate in patients with CKD, whereas the presence of diabetes mellitus and use of renin–angiotensin–aldosterone system inhibitors were not associated with urinary potassium excretion in this study.

  12. Pharmacokinetics of TJ-8117 (Onpi-to), a drug for renal failure (I): Plasma concentration, distribution and excretion of [3H]-(-)epicatechin 3-O-gallate in rats and dogs.

    Science.gov (United States)

    Takizawa, Yukiho; Nishimura, Hiroaki; Morota, Takashi; Tomisawa, Hiroki; Takeda, Shuichi; Aburada, Masaki

    2004-01-01

    TJ-8117 (Onpi-to) is an herbal medicine extracted from a mixture of five crude medicinals (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active components of TJ-8117, was labeled with tritium and added to TJ-8117. Pharmacokinetics in plasma, tissue distribution and excretion of radioactivity were investigated following a single oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in rats and dogs. 1. Following oral administration of [3H]TJ-8117, radioactivity exhibited linear pharmacokinetics in Cmax. Linearity of AUC(0-72 h) was lost at the highest dose of [3H]TJ-8117. Cmax and AUC(0-72 h) were higher in female rats than in male rats, a finding which suggested a sex difference in rats. Plasma levels of radioactivity displayed curves with one peak in dogs, which suggested a species difference between rats and dogs. 2. No accumulation was observed in any tissues in male rats. 3. Within 168 h after administration of [3H]TJ-8117 to male rats, 18.7%, 84.1% and 0.9% of the dose was excreted in urine, feces and expired air, respectively. Data from bile-duct cannulated rats indicated that at least 18.4% of the dose was absorbed.

  13. A Diet High in Meat Protein and Potential Renal Acid Load Increases Absorption and Urinary Excretion of Calcium, As Well As Serum IGF-I in Postmenopausal Women

    Science.gov (United States)

    Objective: The objective was to determine the effect of increasing protein and potential renal acid load (PRAL) on Ca retention and markers of bone metabolism. Methods: In a randomized crossover design, twenty postmenopausal women consumed two diets: one low protein, low PRAL (LPLP) and one high pr...

  14. Identification of a mechanism by which the methylmercury antidotes N-acetylcysteine and dimercaptopropanesulfonate enhance urinary metal excretion: transport by the renal organic anion transporter-1.

    Science.gov (United States)

    Koh, Albert S; Simmons-Willis, Tracey A; Pritchard, John B; Grassl, Steven M; Ballatori, Nazzareno

    2002-10-01

    N-Acetylcysteine (NAC) and dimercaptopropanesulfonate (DMPS) are sulfhydryl-containing compounds that produce a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned animals, but the molecular mechanism for this effect is unknown. NAC and DMPS are themselves excreted in urine in high concentrations. The present study tested the hypothesis that the complexes formed between MeHg and these anionic chelating agents are transported from blood into proximal tubule cells by the basolateral membrane organic anion transporters (Oat) 1 and Oat3. Xenopus laevis oocytes expressing rat Oat1 showed increased uptake of [(14)C]MeHg when complexed with either NAC or DMPS but not when complexed with L-cysteine, glutathione, dimercaptosuccinate, penicillamine, or gamma-glutamylcysteine. In contrast, none of these MeHg complexes were transported by Oat3-expressing oocytes. The apparent K(m) values for Oat1-mediated transport were 31 +/- 2 microM for MeHg-NAC and 9 +/- 2 microM for MeHg-DMPS, indicating that these are relatively high-affinity substrates. Oat1-mediated uptake of [(14)C]MeHg-NAC and [(14)C]MeHg-DMPS was inhibited by prototypical substrates for Oat1, including p-aminohippurate (PAH), and was trans-stimulated when oocytes were preloaded with 2 mM glutarate but not glutamate. Conversely, efflux of [(3)H]PAH from Oat1-expressing oocytes was trans-stimulated by glutarate, PAH, NAC, DMPS, MeHg-NAC, MeHg-DMPS, and a mercapturic acid, indicating that these are transported solutes. [(3)H]PAH uptake was competitively inhibited by NAC (K(i) of 2.0 +/- 0.3 mM) and DMPS (K(i) of 0.10 +/- 0.02 mM), providing further evidence that these chelating agents are substrates for Oat1. These results indicate that the MeHg antidotes NAC and DMPS and their mercaptide complexes are transported by Oat1 but are comparatively poor substrates for Oat3. This is the first molecular identification of a transport mechanism by which these antidotes may enhance urinary excretion of

  15. Renal-Stone Risk Assessment During Space Shuttle Flights

    Science.gov (United States)

    Whitson, Peggy A.; Pietrzyk, Robert A.; Pak, Charles Y. C.

    1996-01-01

    The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. 24-hr urine samples were collected prior to, during space flight, and following landing. Urinary factors associated with renal stone formation were analyzed and the relative urinary supersaturation ratios of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. Food and fluid consumption was recorded for a 48-hr period ending with the urine collection. Urinary composition changed during flight to favor the crystallization of stone-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. The importance of the hypercalciuria was noted since renal excretion was high relative to the intake.

  16. Renal lithiasis and nutrition

    OpenAIRE

    Prieto Rafel M; Costa-Bauza Antonia; Grases Felix

    2006-01-01

    Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of...

  17. [The characteristics or urolithiasis in flight personnel and the treatment results using a method of extracorporeal shockwave lithotripsy on the Russian lithotripter Urat-P2].

    Science.gov (United States)

    Garilevich, B A; Avdeĭchuk, Iu I

    1995-01-01

    Urolithiasis occurs more frequently in the pilots than in the ground-service personnel. To decrease a damaging effect of the focused shock waves on the renal tissue while using remote lithotripsy technique, a new domestic-certified lithotriptor "URAT-P2" which shows a significantly low energy of shock wave with sufficient effectiveness of crushing the renal stones, is devised. Urolithiasis in the pilots is apparent at the early stages of its development and its complicated forms are less common than in the subjects of other professions. The stones are predominantly located in the renal calyces (73,3% of cases), in the left kidney and urethra in 63,3% of cases and there were urate stones in 40% of cases. The clinical use of the URAT-P2 complex in 30 pilots indicated that it holds advantages over the production domestic-certified lithotriptor. The stones are crushed in all the patients but the complications associated with a negative effect of the focused shock waves on the renal tissue are absent. The use of the new lithotriptor for treating urolithiasis in the pilots will allow one to improve the treatment response and to maintain professional worthiness of the pilots for a long time.

  18. Colloidal properties of biomacromolecular solutions: Towards urate oxidase crystal design

    Science.gov (United States)

    Bonneté, Françoise

    2013-02-01

    Crystallization of biological macromolecules is governed by weak interaction forces, attractive and repulsive. Knowledge of solution properties, via second virial coefficient measurements, makes it possible to select physico-chemical parameters that govern and control phase diagrams and thus to grow crystals for specific applications (bio-crystallography or pharmaceutical processes). We highlight here with urate oxidase a salting-in effect that increases its solubility and the depletion effect of amphiphilic polymer, at a polymer concentration above its cmc, in order to grow diffracting crystals of urate oxidase. These two effects were used to grow crystals for high pressure crystallography and in a purification process.

  19. Acute kidney injury observed during phase 1 clinical trials of a novel xanthine oxidase/URAT1 dual inhibitor PF-06743649.

    Science.gov (United States)

    Dua, Pinky; Gurrell, Rachel; Kirby, Simon; Sudworth, Maria; Loudon, Peter T

    2016-08-01

    The objective of these clinical studies was to assess the safety and urate lowering activity of a novel urate transporter 1 (URAT1)/ xanthine oxidase (XO) inhibitor PF-06743649 in healthy subjects and gout patients. Escalating doses of PF-06743649 or placebo were given to healthy young subjects, healthy elderly subjects and gout patients. Serum uric acid (sUA) and urinary pharmacodynamic markers were assayed, and safety was assessed by collection of adverse events and assessment of safety labs, ECGs and vital signs. Administration of PF-06743649 led to rapid decrease in sUA in all cohorts; in gout patients, a change from baseline of 69 % was observed for the 40 mg dose. Urinary and serum biomarkers were consistent with inhibition of both URAT1 and XO. Although dosing was otherwise well tolerated, two subjects experienced serious adverse events of acute kidney injury. Both subjects exhibited increased serum creatinine and blood urea nitrogen in the first 3 days post first dose and were hospitalised. One subject exhibited oliguria for the first 24 h. Both subjects made a complete recovery with minimal intervention. PF-06743649 was effective at rapidly lowering sUA, but further development was terminated for an identified renal safety risk.

  20. Renal lithiasis and nutrition.

    Science.gov (United States)

    Grases, Felix; Costa-Bauza, Antonia; Prieto, Rafel M

    2006-09-06

    Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified through diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine) is discussed.

  1. Renal lithiasis and nutrition

    Directory of Open Access Journals (Sweden)

    Prieto Rafel M

    2006-09-01

    Full Text Available Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine is discussed.

  2. 普萘洛尔对盐酸二甲双胍大鼠肾排泄的影响%Effects of co-administration of propranolol on the renal excretion of metformin hydrochloride in rats

    Institute of Scientific and Technical Information of China (English)

    任江霞; 周燕; 张国强; 赵晶; 魏玉辉; 武新安

    2013-01-01

    目的:考察普萘洛尔对盐酸二甲双胍肾排泄的影响.方法:20只健康Wistar雄性大鼠随机分为2组,一组尾静脉注射盐酸二甲双胍和普萘洛尔,另一组注射盐酸二甲双胍,于给药后收集各时间段(0~2,2~4,4~6,6~8,8~10,10~12,12~24 h)的尿液样品.用高效液相色谱法测定二甲双胍尿药浓度,用DAS 2.0软件计算二甲双胍的药动学参数后对数据进行分析.结果:联合用药组的药动学参数t1/2,Ke[(2.8±0.4)h,(0.25±0.58)h-1]较二甲双胍组[(2.11±0.30)h,(0.34±0.45)h-1]存在统计学差异(P<0.05),但总尿排量较二甲双胍组无显著性差异(P>0.05).结论:普萘洛尔对健康Wistar雄鼠盐酸二甲双胍的肾排泄速率有显著影响,可能与其竞争性抑制了肾脏rOCT2有关.%OBJECTIVE To study the effects of co-administration of propranolol on the renal excretion of metformin hydrochloride in rats.METHODS 20 young male rats were randomly divided into 2 equal groups.After the rats of the co-administration group treated with both propranolol and metformin hydrochloride,metformin hydrochloride group were treated only with metformin hydrochloride via tail vein injection,the urine samples were collected in 0-2,2-4,4-6,6-8,8-10,10-12 and 12 -24 h.The concentrations of metformin hydrochloride in urine were determined by high performance liquid chromatography.According to the concentration of urine,the software of DAS 2.0 was used to calculate the pharmacokinetic parameters.RESULTS The significantly changed pharmacokinetic parameters of the metformin group and the testing group (P< 0.05) in rats:t1/2 were (2.8 ± 0.4) and (2.11 ± 0.30) h,respectively;Ke were (0.25 ± 0.58) and (0.34 ± 0.45) h-1 respectively; while the total urine discharge of metformin was not significantly changed (P>0.05).CONCLUSION Propranolol had significant effect on the renal excretion process of metformin hydrochloride in rats; the possible reason was that propranolol may

  3. Using serum urate as a validated surrogate end point for flares in patients with gout

    DEFF Research Database (Denmark)

    Morillon, Melanie B; Stamp, Lisa; Taylor, William;

    2016-01-01

    INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels......, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate...

  4. Oxidation of urate in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Tullson, P. C.; Richter, Erik

    1997-01-01

    The purpose of the present study was to investigate whether high metabolic stress to skeletal muscle, induced by intensive exercise, would lead to an oxidation of urate to allantoin in the exercised muscle. Seven healthy male subjects performed short term (4.39 +/- 0.04 [+/-SE] min) exhaustive cy...

  5. Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders.

    Science.gov (United States)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

    2016-12-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. Copyright © 2016 by the American Society of Nephrology.

  6. Participação da excreção renal de cálcio, fósforo, sódio e potássio na homeostase em cães sadios e cães com doença renal crônica Participation of renal excretion of calcium, phosphorus, sodium and potassium on the homeostasis in healthy dogs and in dogs with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Pedro P Martínez

    2010-10-01

    Full Text Available Na doença renal crônica (DRC a manutenção da homeostase de água e sódio é o primeiro problema a ser contornado pelo organismo e com o agravamento das lesões renais surgem outros problemas graves relacionados à homeostase de cálcio e fósforo. O presente estudo tem por escopo avaliar a excreção renal de cálcio, fósforo, sódio e potássio, e o perfil sérico destes eletrólitos em cães normais e em cães com DRC naturalmente adquirida. Foram avaliados três grupos de cães adultos, machos ou fêmeas, de raças variadas. Animais normais compuseram o grupo controle (G1 e os cães com DRC foram distribuídos em dois grupos de acordo com os estágios de comprometimento da função renal (G2 e G3, respectivamente, estágios 1-2 e estágios 3-4, descritos pela IRIS 2006 staging CKD. Os cães do G3 apresentaram aumento das concentrações séricas de cálcio ionizado e fósforo, além de diminuição da concentração sérica de sódio. Quanto à excreção renal dos eletrólitos analisados, os animais dos grupos G1 e G2 apresentaram diminuição de carga filtrada e aumento de excreção fracionada, mas as excreções urinárias não variaram significativamente. Os resultados são indicativos de que os rins de cães com DRC podem manter a excreção urinária dos eletrólitos em valores se melhantes aos dos normais. O mecanismo envolve aumento da excreção fracionada na medida em que haja diminuição da filtração glomerular. Esse processo de compensação, entretanto, pode perder a eficiência nos estágios mais avançados da enfermidade no que se refere à manutenção das concentrações séricas de fósforo e sódio.In chronic kidney disease (CKD, the first problem to be solved by the organism is to maintain water and sodium homeostasis and, with the worsening of the renal injuries, other severe problems related to the calcium and phosphorus homeostasis emerge. The present study has the purpose to evaluate the renal excretion and

  7. 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

  8. Nickel Dermatitis - Nickel Excretion

    DEFF Research Database (Denmark)

    Menné, T.; Thorboe, A.

    1976-01-01

    Nickel excretion in urine in four females -sensitive to nickel with an intermittent dyshidrotic eruption was measured with flameless atomic absorption. Excretion of nickel was found to be increased in association with outbreaks of vesicles. The results support the idea that the chronic condition...... was maintained by ingestion of nickel in food....

  9. Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO.

    Science.gov (United States)

    Michiel, Magalie; Perchat, Nadia; Perret, Alain; Tricot, Sabine; Papeil, Aude; Besnard, Marielle; de Berardinis, Véronique; Salanoubat, Marcel; Fischer, Cécile

    2012-12-01

    In aerobic cells, urate is oxidized to 5-hydroxyisourate by two distinct enzymes: a coenzyme-independent urate oxidase (EC 1.7.3.3) found in eukaryotes and bacteria like Bacillus subtilis and a prokaryotic flavoprotein urate hydroxylase (HpxO) originally found in some Klebsiella species. More cases of analogous or non-homologous isofunctional enzymes (NISE) for urate catabolism have been hypothesized by inspecting bacterial genomes. Here, we used a functional complementation approach in which a candidate gene for urate oxidation is integrated by homologous recombination in the Acinetobacter baylyi ADP1 genome at the locus of its original hpxO gene. Catabolism of urate was restored in A. baylyi ADP1 expressing a FAD-dependent protein from Xanthomonas campestris, representing a new urate hydroxylase family that we called HpyO. This enzyme was kinetically characterized and compared with other HpxO enzymes. In contrast to the latter, HpyO is a typical Michaelian enzyme. This work provides the first experimental evidences for the function of HpyO in bacterial urate catabolism and establishes it as a NISE of HpxO. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  10. The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age

    Directory of Open Access Journals (Sweden)

    Jackson Robert L

    2012-03-01

    Full Text Available Abstract Background The incidence of gout rises with increasing age. Management of elderly (≥65 years gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial. Methods Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function once daily. Flare prophylaxis was provided throughout the study duration. Study endpoints were the percent of elderly subjects with sUA Results Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0% than febuxostat 40 mg (61.7%; p p p = 0.029. In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028 and febuxostat 80 mg (82.5%; p p p = 0.011 groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments. Conclusions These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated. Trial registration clinicaltrials.gov NCT#00430248

  11. Light-chain nephropathy in patient with renal carcinoma.

    OpenAIRE

    Enia, G.; Maringhini, S; L'Abbate, A; Zoccali, C.; Maggiore, Q

    1981-01-01

    Paraneoplastic syndromes are often associated with renal parenchymal tumours. This report describes a case of renal-cell carcinoma with kappa-chain nephropathy. The patient, a 60-year-old man, had renal tubular dysfunction, shown by low serum concentrations of urate and phosphate. Kappa-chains were found in both serum and urine, but no lambda-chains were found. Investigations showed a clear-cell carcinoma, and the patient underwent a radical nephrectomy. Two years after operation serum phosph...

  12. FARMACOFISIOLOGÍA RENAL

    Directory of Open Access Journals (Sweden)

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  13. Kidney ageing and renal excretion of amylase.

    Science.gov (United States)

    Brohée, D; Rondelez, L; Bain, H; de Maertelaer, V

    1982-01-01

    In a cross-sectional study, the amylase to creatinine clearance ratio (ACCR) was determined in 180 patients, age range 18-93 years. An inverse correlation was found between ACCR and creatinine clearance (r = -0.40, p less than 0.001) in keeping with the known inverse relationship between the sieving fraction of macromolecules and the glomerular filtration rate. The fractional clearance of amylase was not significantly affected by amylasemia nor by age when the creatinine clearance was also considered in a multiple regression analysis. No increase in ACCR was observed in patients with low molecular weight proteinuria or with induced urine dilution. The authors assume that the tubular reabsorption of amylase is minimal and that the enhancement of ACCR in the elderly mainly reflects modifications in the glomerular filtration dynamics.

  14. Mendelian randomization analysis to examine for a causal effect of urate on bone mineral density.

    Science.gov (United States)

    Dalbeth, Nicola; Topless, Ruth; Flynn, Tanya; Cadzow, Murray; Bolland, Mark J; Merriman, Tony R

    2015-06-01

    In observational studies, serum urate concentrations are positively associated with bone mineral density (BMD) and reduced risk of fragility fractures, raising the possibility that urate is a direct mediator of bone density. We used Mendelian randomization analysis to examine whether urate has a causal effect on BMD. We analyzed data from the Generation 3 cohort in the Framingham Heart Study (FHS) (N = 2501 total; 1265 male, 1236 female). A weighted genetic urate score was calculated using the SLC2A9, ABCG2, SLC17A1, SLC22A11, and SLC22A12 single-nucleotide polymorphisms (SNPs) that explains 3.4% of the variance in serum urate. Mendelian randomization analysis was performed using the two-stage least squares method with >80% power at α = 0.05 to detect an effect size equivalent to that observed in the ordinary least squares analysis between serum urate and total femur BMD. A strong association between serum urate and BMD was observed in the crude ordinary least squares analysis (total femur crude beta = 0.47, p = 1.7E-51). In the two-stage least squares analysis using the weighted genetic urate score as the instrumental variable, no significant relationship was observed between serum urate and BMD (total femur crude beta =-0.36, p = 0.06). Similar findings were observed in both the male and female subgroups, and there was no evidence for causality when individual SNPs were analyzed. Serum urate is strongly associated with BMD. However, controlling for confounders by Mendelian randomization analysis does not provide evidence that increased urate has a causal effect on increasing BMD. © 2014 American Society for Bone and Mineral Research.

  15. Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa

    DEFF Research Database (Denmark)

    Weihe, Johan Petur; Birger Morillon, Melanie; Lambrechtsen, Jess

    Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa......Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa...

  16. Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa

    DEFF Research Database (Denmark)

    Weihe, Johan Petur; Birger Morillon, Melanie; Lambrechtsen, Jess

    Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa......Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa...

  17. Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa

    DEFF Research Database (Denmark)

    Weihe, Johan Petur; Birger Morillon, Melanie; Lambrechtsen, Jess;

    2014-01-01

    Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa......Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa...

  18. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with se

  19. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  20. Are hummingbirds facultatively ammonotelic? Nitrogen excretion and requirements as a function of body size.

    Science.gov (United States)

    McWhorter, Todd J; Powers, Donald R; Martínez Del Rio, Carlos

    2003-01-01

    Most birds are uricotelic. An exception to this rule may be nectar-feeding birds, which excrete significant amounts of ammonia under certain conditions. Although ammonia is toxic, because it is highly water soluble its excretion may be facilitated in animals that ingest and excrete large amounts of water. Bird-pollinated plants secrete carbohydrate- and water-rich floral nectars that contain exceedingly little protein. Thus, nectar-feeding birds are faced with the dual challenge of meeting nitrogen requirements while disposing of large amounts of water. The peculiar diet of nectar-feeding birds suggests two hypotheses: (1) these birds must have low protein requirements, and (2) when they ingest large quantities of water their primary nitrogen excretion product may be ammonia. To test these hypotheses, we measured maintenance nitrogen requirements (MNR) and total endogenous nitrogen losses (TENL) in three hummingbird species (Archilochus alexandri, Eugenes fulgens, and Lampornis clemenciae) fed on diets with varying sugar, protein, and water content. We also quantified the form in which the by-products of nitrogen metabolism were excreted. The MNR and TENL of the hummingbirds examined were exceptionally low. However, no birds excreted more than 50% of nitrogen as ammonia or more nitrogen as ammonia than urates. Furthermore, ammonia excretion was not influenced by either water or protein intake. The smallest species (A. alexandri) excreted a significantly greater proportion (>25%) of their nitrogenous wastes as ammonia than the larger hummingbirds ( approximately 4%). Our results support the hypothesis that nectar-feeding birds have low protein requirements but cast doubt on the notion that they are facultatively ammonotelic. Our data also hint at a possible size-dependent dichotomy in hummingbirds, with higher ammonia excretion in smaller species. Differences in proportionate water loads and/or postrenal modification of urine may explain this dichotomy.

  1. Urinary sulphate excretion and progression of diabetic nephropathy in Type 1 diabetes

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Bakker, S J L; Hansen, H P

    2013-01-01

    Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy....

  2. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  3. Serum urate and probability of dopaminergic deficit in early ‘Parkinson disease’

    Science.gov (United States)

    Schwarzschild, Michael A.; Marek, Kenneth; Eberly, Shirley; Oakes, David; Shoulson, Ira; Jennings, Danna; Seibyl, John; Ascherio, Alberto

    2011-01-01

    Objective Investigate whether higher levels of urate, an antioxidant linked to a lower likelihood of developing Parkinson disease (PD), is also a predictor of having a dopamine transporter brain scan without evidence of dopaminergic deficit (SWEDD). Methods In a cross-sectional study of 797 mildly affected, untreated parkinsonian subjects diagnosed with early PD in the Parkinson Research Examination of CEP-1347 Trial (PRECEPT), we investigated the relationship at baseline between serum urate and striatal dopamine transporter density, determined by single-photon emission computed-tomography of iodine-123-labeled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([123I]β-CIT) uptake. A SWEDD was defined as lowest putamen [123I]β-CIT > 80% age-expected putamen DAT density. Results Odds of having a SWEDD rose across increasing quintiles of urate level, with an age- and gender-adjusted odds ratio of 3.2 comparing the highest to the lowest urate quintile; 95% CI: 1.5 to 7.2; p for trend = 0.0003) and remained significant after adjusting for potential confounding factors. The association was significant in men but not women, regardless of whether common or sex-specific quintiles of urate were used. Conclusions Higher levels of urate were associated with a greater likelihood of a SWEDD amongst subjects with early untreated parkinsonism in the PRECEPT study. The findings support the diagnostic utility of urate in combination with other determinants. PMID:21538532

  4. Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    Full Text Available BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5 against 6-hydroxydopamine (6-OHDA- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2 accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1 expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC and heme oxygenase-1 (HO-1, both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

  5. Urate oxidase purification by salting-in crystallization: towards an alternative to chromatography.

    Directory of Open Access Journals (Sweden)

    Marion Giffard

    Full Text Available BACKGROUND: Rasburicase (Fasturtec® or Elitek®, Sanofi-Aventis, the recombinant form of urate oxidase from Aspergillus flavus, is a therapeutic enzyme used to prevent or decrease the high levels of uric acid in blood that can occur as a result of chemotherapy. It is produced by Sanofi-Aventis and currently purified via several standard steps of chromatography. This work explores the feasibility of replacing one or more chromatography steps in the downstream process by a crystallization step. It compares the efficacy of two crystallization techniques that have proven successful on pure urate oxidase, testing them on impure urate oxidase solutions. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigate the possibility of purifying urate oxidase directly by crystallization from the fermentation broth. Based on attractive interaction potentials which are known to drive urate oxidase crystallization, two crystallization routes are compared: a by increased polymer concentration, which induces a depletion attraction and b by decreased salt concentration, which induces attractive interactions via a salting-in effect. We observe that adding polymer, a very efficient way to crystallize pure urate oxidase through the depletion effect, is not an efficient way to grow crystals from impure solution. On the other hand, we show that dialysis, which decreases salt concentration through its strong salting-in effect, makes purification of urate oxidase from the fermentation broth possible. CONCLUSIONS: The aim of this study is to compare purification efficacy of two crystallization methods. Our findings show that crystallization of urate oxidase from the fermentation broth provides purity comparable to what can be achieved with one chromatography step. This suggests that, in the case of urate oxidase, crystallization could be implemented not only for polishing or concentration during the last steps of purification, but also as an initial capture step, with minimal

  6. Dependency of renal thorium and uranium excretion from age and gender in non-exposed persons; Abhaengigkeit der renalen Thorium- und Uranausscheidung von Geschlecht und Alter bei nicht-exponierten Personen

    Energy Technology Data Exchange (ETDEWEB)

    Werner, E.; Roth, P.; Wendler, I.; Schramel, P. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany)

    1998-12-31

    For the assessment of an occupational incorporation of thorium or uranium it is essential to know which portion of the measured activity is caused by natural sources. In the present study the daily urinary excretion of {sup 232}Th and {sup 238}U was measured in 76 healthy volunteers. None of them had a previous history of occupational exposure to thorium or uranium. The data show no difference in the excretion between male and female subjects. Whereas in adolescents only little excretion of {sup 232}Th and {sup 238}U is found, a significantly increasing variation of thorium and uranium in urine is observed with progressing age. From the data obtained an age-related upper limit of {sup 232}Th and {sup 238}U urinary excretion can be derived, which may be useful for the interpretation of a measured value due to the occupational exposure. (orig.) [Deutsch] Fuer die Beurteilung einer beruflich bedingten Inkorporation von Thorium oder Uran ist es wichtig zu wissen, welcher Artikel am gemessenen Wert auf natuerliche Quellen zurueckzufuehren ist. In der vorliegenden Studie wurde die taegliche Ausscheidung von{sup 232}Th und {sup 238}U im Urin bei 76 gesunden Personen im Alter von 7 bis 84 Jahren mit der ICP-MS gemessen. Keine dieser Personen hatte vorher beruflichen Umgang mit Thorium oder Uran gehabt. Die Daten zeigen keinen Unterschied zwischen Frauen und Maennern. Waehrend bei Jugendlichen nur geringe Ausscheidungswerte beobachtet werden, tritt mit zunehmendem Lebensalter eine erhebliche Vergroesserung des Variationsbereichs ein. Aus den erhobenen Daten ergibt sich eine altersbezogene Obergrenze fuer die {sup 232}Th- und {sup 238}U-Ausscheidung im Urin, die fuer die Interpretation eines Messwertes bei beruflicher Exposition herangezogen werden kann. (orig.)

  7. Urinary excretion of Tamm-Horsfall protein and epidermal growth factor in chronic nephropathy

    DEFF Research Database (Denmark)

    Torffvit, O; Jørgensen, P E; Kamper, A L

    1998-01-01

    rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C...... analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy....

  8. VizieR Online Data Catalog: Binary star discoveries in the URAT1 catalog (Nicholson, 2015)

    Science.gov (United States)

    Nicholson, M. P.

    2015-05-01

    Astrometric and photometric data are presented for 9450 common proper motion binary star system using results from the first U.S. Naval Observatory Astrometric Robotic Telescope Catalog (URAT1) (1 data file).

  9. Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2008-03-01

    Full Text Available Andrea Pession, Fraia Melchionda, Claudia CastelliniOncologia Ematologia Pediatrica “Lalla Seràgnoli”, Clinica Pediatrica, Università degli Studi di Bologna, Bologna, ItalyAbstract: Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase (recombinant urate oxidase has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it. Rasburicase acts at the end of the purine catabolic pathway and, unlike allopurinol, does not induce accumulation of xanthine or hypoxanthine. Its rapid onset of action and the ability to lower pre-existing elevated uric acid levels are the advantages of rasburicase over allopurinol. Rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patient’s electrolyte status, and reverse renal insufficiency. The drug, initially studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma, seems to show comparable benefit in adults with similar lymphoid malignancies or at high risk of tumor lysis syndrome. Current and future trials will evaluate alternative doses and different schedules of rasburicase to maintain its efficacy while reducing its cost. The review provides a comprehensive and detailed review of pathogenesis, laboratory, and clinical presentation of TLS together with clinical studies already performed both in pediatric and adult patients.Keywords: tumor lysis syndrome, urate oxidase, rasburicase, allopurinol, uric acid

  10. Urine alkalization facilitates uric acid excretion

    Directory of Open Access Journals (Sweden)

    Seyama Issei

    2010-10-01

    Full Text Available Abstract Background Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of facilitated excretion of uric acid by change in urine pH by managing food materials. Methods Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H+-load (acid diet and others composed of less protein but vegetable-fruit rich food materials (alkali diet. Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+ and anions (Cl-,SO42-,PO4- necessary for the estimation of acid-base balance were measured. Results Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] +organic acid-gut alkai were linearly related with those of the excretion of acid (titratable acidity+ [NH4+] - [HCO3-], indicating that H+ in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body.

  11. Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia.

    Science.gov (United States)

    Maesaka, John K; Imbriano, Louis; Mattana, Joseph; Gallagher, Dympna; Bade, Naveen; Sharif, Sairah

    2014-12-08

    Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to treat virtually all hyponatremics exposes the need to resolve the diagnostic and therapeutic dilemma of deciding whether to water restrict a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or administer salt and water to a renal salt waster. In this review, we briefly discuss the pathophysiology of SIADH and renal salt wasting (RSW), and the difficulty in differentiating SIADH from RSW, and review the origin of the perceived rarity of RSW, as well as the value of determining fractional excretion of urate (FEurate) in differentiating both syndromes, the high prevalence of RSW which highlights the inadequacy of the volume approach to hyponatremia, the importance of changing cerebral salt wasting to RSW, and the proposal to eliminate reset osmostat as a subtype of SIADH, and finally propose a new algorithm to replace the outmoded volume approach by highlighting FEurate. This algorithm eliminates the need to assess the volume status with less reliance on determining urine sodium concentration, plasma renin, aldosterone and atrial/brain natriuretic peptide or the BUN to creatinine ratio.

  12. Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia

    Directory of Open Access Journals (Sweden)

    John K. Maesaka

    2014-12-01

    Full Text Available Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to treat virtually all hyponatremics exposes the need to resolve the diagnostic and therapeutic dilemma of deciding whether to water restrict a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH or administer salt and water to a renal salt waster. In this review, we briefly discuss the pathophysiology of SIADH and renal salt wasting (RSW, and the difficulty in differentiating SIADH from RSW, and review the origin of the perceived rarity of RSW, as well as the value of determining fractional excretion of urate (FEurate in differentiating both syndromes, the high prevalence of RSW which highlights the inadequacy of the volume approach to hyponatremia, the importance of changing cerebral salt wasting to RSW, and the proposal to eliminate reset osmostat as a subtype of SIADH, and finally propose a new algorithm to replace the outmoded volume approach by highlighting FEurate. This algorithm eliminates the need to assess the volume status with less reliance on determining urine sodium concentration, plasma renin, aldosterone and atrial/brain natriuretic peptide or the BUN to creatinine ratio.

  13. Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals

    Directory of Open Access Journals (Sweden)

    Christine eSchorn

    2012-12-01

    Full Text Available In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot and swollen arthritic joints.Here we report the in vitro effect of MSU crystals on blood granulocytes and analyse their contribution to granuloma formation and neutrophil extracellular traps (NETs formation (NETosis in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS-dependent manner. Indeed, blocking ROS (e.g. the oxidative burst by various antioxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonisation of NETs, as a prerequisite for their clearance. The established dead cells’ opsonins C3b, galectin-9 and CRP decorated the residual dead cells` corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (I MSU crystals are strong inducers of ROS-dependent NETosis and (II that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement and galectin mediated phagocytic clearance.

  14. Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter.

    NARCIS (Netherlands)

    Smeets, P.H.E.; Aubel, R.A.M.H. van; Wouterse, A.C.; Heuvel, J.J.T.M.; Russel, F.G.M.

    2004-01-01

    p-Aminohippurate (PAH) is the classical substrate used in the characterization of organic anion transport in renal proximal tubular cells. Although basolateral transporters for PAH uptake from blood into the cell have been well characterized, there is still little knowledge on the apical urinary eff

  15. A diet high in meat protein and potential renal acid load increases fractional Ca absorption and urinary Ca excretion, without affecting markers of bone resorption or formation in postmenopausal women

    Science.gov (United States)

    Objective: The objective was to determine the effects of high dietary protein (mostly meat) and high potential renal acid load (PRAL) on calcium (Ca) balance and markers of bone metabolism. Methods: In a randomized crossover design, sixteen healthy postmenopausal women consumed two diets: one with l...

  16. Lactulose and renal failure.

    Science.gov (United States)

    Vogt, B; Frey, F J

    1997-01-01

    The introduction of lactulose as a new therapeutic agent for treatment of hepatic encephalopathy was a major breakthrough in this field. It was hypothesized that lactulose might prevent postoperative renal impairment after biliary surgery in patients with obstructive jaundice. The presumable mechanism purported was the diminished endotoxinemia by lactulose. Unfortunately, such a reno-protective effect has not been shown conclusively until now in clinical studies. In chronic renal failure lactulose is known to promote fecal excretion of water, sodium, potassium, amonium, urea, creatinine and protons. Thus, lactulose could be useful for the treatment of chronic renal failure. However, compliance to the therapy represents a major problem.

  17. Urinary excretion of Tamm-Horsfall protein and epidermal growth factor in chronic nephropathy

    DEFF Research Database (Denmark)

    Torffvit, O; Jørgensen, P E; Kamper, A L

    1998-01-01

    with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration...... rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C...... analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy....

  18. Treatment approaches and adherence to urate-lowering therapy for patients with gout

    Directory of Open Access Journals (Sweden)

    Aung T

    2017-04-01

    Full Text Available Thanda Aung,* Gihyun Myung,* John D FitzGerald Division of Rheumatology/Department of Internal Medicine, University of California, Los Angeles, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gout is the most common inflammatory arthritis characterized by painful disabling acute attacks. It is caused by hyperuricemia and deposition of urate crystals in and around the joints. Long-standing untreated hyperuricemia can lead to chronic arthritis with joint damage, tophi formation and urate nephropathy. Gout is associated with significant morbidity and health care associated cost. The goal of long-term therapy is to lower the serum urate level to promote dissolution of urate crystals, reduce recurrent acute gout flares, resolve tophi and prevent joint damage. Despite the presence of established gout treatment guidelines and effective medications to manage gout, patient outcomes are often poor. Etiology for these shortcomings is multifactorial including both physician and patient characteristics. Poor adherence to urate-lowering therapy (ULT is prevalent and is a significant contributor to poor patient outcomes. This article reviews the treatment strategies for the management of hyperuricemia in chronic gout, gaps in quality of care in gout management, factors contributing to poor adherence to ULT and discusses potential interventions to achieve improved gout-related outcomes. These interventions include initiation of prophylactic anti-inflammatory medication when starting ULT, frequent follow-ups, regular serum urate monitoring and improved patient education, which can be achieved through pharmacist- or nurse-assisted programs. Interventions such as these could improve adherence to ULT and, ultimately, result in optimal gout-related outcomes. Keywords: gout, adherence, urate-lowering therapy 

  19. Urate-lowering therapy for the management of gout: a summary of 2 Cochrane reviews.

    Science.gov (United States)

    Kydd, Alison S; Seth, Rakhi; Buchbinder, Rachelle; Falzon, Louise; Edwards, Christopher J; van der Heijde, Désirée M; Bombardier, Claire

    2014-09-01

    To systematically review the evidence on the efficacy, safety, and cost-effectiveness of urate-lowering therapy for gout: xanthine oxidase inhibitors (allopurinol and febuxostat), uricosuric medications (benzbromarone, probenecid and sulfinpyrazone), and uricases (pegloticase and rasburicase). A systematic review was performed as part of the 3e (Evidence, Expertise, Exchange) Initiative on Gout. The primary efficacy outcomes were frequency of acute gout attacks, study participant withdrawal due to adverse events, and cost-effectiveness. Serum urate-lowering was a secondary outcome and was the most commonly reported outcome in the included trials. The search identified 17 articles for efficacy, 31 for safety, and 3 for cost-effectiveness. The main outcome described in these studies was serum urate-lowering. Allopurinol, febuxostat, and pegloticase are all effective at lowering serum urate compared to placebo and febuxostat (≥ 80 mg) was more effective at lowering serum urate than allopurinol. Compared to probenecid, benzbromarone was more effective at lowering serum urate. Regarding acute gout attacks, pegloticase and febuxostat (≥ 120 mg) resulted in more acute attacks than placebo. Regarding the primary safety outcome, more withdrawals due to adverse events were seen only when pegloticase was compared to placebo. The two trials of cost-effectiveness were inconclusive. There is currently moderate quality data supporting the efficacy and safety of allopurinol, febuxostat, benzbromarone, and probenecid in gout. Pegloticase, while efficacious, is associated with more withdrawals due to adverse events and infusion reactions. There is insufficient evidence currently with respect to the cost-effectiveness or the most optimal sequencing of urate-lowering therapy.

  20. Effect of pharmacological lowering of plasma urate on exercise-induced oxidative stress.

    Science.gov (United States)

    McAnulty, S R; Hosick, P A; McAnulty, L S; Quindry, J C; Still, L; Hudson, M B; Dibarnardi, A N; Milne, G L; Morrow, J D; Austin, M D

    2007-12-01

    Urate is a metabolic end product of purine metabolism that contributes about 66% of the antioxidant capacity of plasma. The objective of this study was to evaluate the importance of plasma urate as an antioxidant using pharmacological lowering and examining the impact on plasma antioxidant capacity and oxidative stress after intense exercise. Fifteen subjects ran for 45 min at approximately 80% VO2 max under the influence of probenecid (1 g/d) (PRO) or placebo (PLA) in a double-blind, crossover design. Blood samples obtained at baseline, pre-exercise, and immediately post-exercise were analyzed for F2-isoprostanes, lipid hydroperoxides (LHs), ferric-reducing ability of plasma (FRAP), urate, ascorbate (AA), and nitrite. A 2 (group)x2 (time) repeated-measures analysis of variance (ANOVA), one-way ANOVA, Tukey-Kramer multiple comparison tests, and Student's t tests were used for statistical analysis. PRO exhibited lowered urate and FRAP compared with baseline (purate and a diminished antioxidant capacity within the plasma compartment.

  1. Hydrochlorothiazide-induced /sup 131/I excretion facilitated by salt and water

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, K.H. Jr.; Fehr, D.M.; Gelarden, R.T.; White, W.J.; Lang, C.M.; Vesell, E.S.

    Salt intake is restricted under clinical conditions for which thiazide diuretics are customarily used. Dietary iodide intake offsets any effect of thiazide on iodide loss. However, our correlation coefficients relating Na+ to Cl- to I- excretion indicate that as thiazide administration or sodium chloride intake increases renal Na+ and Cl- excretion, I- reabsorption by the nephron coordinately decreases. Increased sodium chloride and water intake by the dog doubled I-excretion rates. Hydrochlorothiazide increased the sodium chloride and water enhanced I-excretion rate as much as eight-fold. Without added NaCl, hydrochlorothiazide increased the excretion rate of 131I by three- to eightfold, acutely. Within five to seven days after 131I oral administration, hydrochlorothiazide (1 or 2 mg/kg twice daily) doubled the rate of 131I disappearance from plasma, reduced the fecal output of 131I, and increased its rate of renal excretion. When hydrochlorothiazide was administered, as much 131I was excreted in the first 24 hours as occurred in 48 hours when sodium chloride and water were given without hydrochlorothiazide. Thiazide administration in customary clinical dosage twice a day with substantial sodium chloride and water for the first two days after exposure to 131I, should therefore facilitate the safe excretion of 131I. This accelerated removal of 131I might be enhanced even more if thyroid uptake of 131I is blocked by administration of potassium iodide, as judged by the greater 131I recovery from thyroidectomized dogs.

  2. Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.

    Science.gov (United States)

    Bulacio, Romina Paula; Anzai, Naohiko; Ouchi, Motoshi; Torres, Adriana Mónica

    2015-08-17

    Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.

  3. Kidney Modelling for FDG Excretion with PET

    Directory of Open Access Journals (Sweden)

    Huiting Qiao

    2007-01-01

    Full Text Available The purpose of this study was to detect the physiological process of FDG's filtration from blood to urine and to establish a mathematical model to describe the process. Dynamic positron emission tomography scan for FDG was performed on seven normal volunteers. The filtration process in kidney can be seen in the sequential images of each study. Variational distribution of FDG in kidney can be detected in dynamic data. According to the structure and function, kidney is divided into parenchyma and pelvis. A unidirectional three-compartment model is proposed to describe the renal function in FDG excretion. The time-activity curves that were picked up from the parenchyma, pelvis, and abdominal aorta were used to estimate the parameter of the model. The output of the model has fitted well with the original curve from dynamic data.

  4. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors

    NARCIS (Netherlands)

    Q. Yang (Qiong Fang); A. Köttgen (Anna); A. Dehghan (Abbas); A.V. Smith (Albert Vernon); N.L. Glazer (Nicole); M-H. Chen (Ming-Huei); D.I. Chasman (Daniel); T. Aspelund (Thor); G. Eiriksdottir (Gudny); T.B. Harris (Tamara); L.J. Launer (Lenore); M.A. Nalls (Michael); D.G. Hernandez (Dena); D.E. Arking (Dan); E. Boerwinkle (Eric); M.L. Grove (Megan); M. Li (Man); W.H. Linda Kao; M. Chonchol (Michel); T. Haritunians (Talin); T. Lumley (Thomas); B.M. Psaty (Bruce); M.G. Shlipak (Michael); S.J. Hwang; M.G. Larson (Martin); C.J. O'Donnell (Christopher); A. Upadhyay (Ashish); P. Tikka-Kleemola (Päivi); A. Hofman (Albert); F. Rivadeneira Ramirez (Fernando); B.H.Ch. Stricker (Bruno); A.G. Uitterlinden (André); G. Paré (Guillaume); A.N. Parker (Alex); P.M. Ridker (Paul); D.S. Siscovick (David); V. Gudnason (Vilmundur); J.C.M. Witteman (Jacqueline); C.S. Fox (Caroline); J. Coresh (Josef)

    2010-01-01

    textabstractBackground - Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum u

  5. Attenuation of gouty arthritis by emodinol in monosodium urate crystal-treated mice.

    Science.gov (United States)

    Chen, Lvyi; Lan, Zhou; Ma, Shuwei; Zhao, Ling; Yang, Xinzhou

    2013-05-01

    A series of studies have recently demonstrated that the release of interleukin 1β induced by monosodium urate crystals is central to the experimental gouty arthritis. Elaeagnus pungens has been traditionally used for the treatment of gouty arthritis in China for more than thousands years. However, there is still little known about the active ingredients and mechanisms of E. pungens against gouty arthritis. Emodinol, as a major triterpene compound in E. pungens, has been seldom reported to have an effect on gouty arthritis. Therefore, the potential beneficial effects and mechanisms of emodinol on gouty arthritis were investigated in this study. Results showed that it significantly ameliorated the hyperalgesia, inflammation, and levels of multiple proinflammatory cytokines in monosodium urate crystals-treated mice. These findings elucidate that emodinol exhibits a prominent effect on improving symptoms of acute gouty arthritis induced by monosodium urate crystals through inhibiting the generation of proinflammatory cytokines.

  6. VizieR Online Data Catalog: 1103 parallaxes and proper motions from URAT (Finch+, 2016)

    Science.gov (United States)

    Finch, C. T.; Zacharias, N.

    2016-07-01

    We present 1103 trigonometric parallaxes and proper motions from the United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT) observations taken at the Naval Observatory Flagstaff Station (NOFS). URAT observes through a single filter (part of the dewar window) to provide a fixed bandpass of about 680 to 760nm. The clear aperture of the USNO astrograph is 206mm with a focal length of only 2m. A single exposure covers 28 square degrees with a resolution of 0.9arcsec/pixel. Each of the four large CCDs in the focal plane covers a 2.65 by 2.65 deg area on the sky. Data of all three years of operations (2012 April to 2015 June) at the NOFS are used here for this parallax investigation. For more details about the project, instrument, and observing the reader is referred to the URAT1 paper (Zacharias et al. 2015, cat. I/329). (3 data files).

  7. Urinary Sodium and Potassium Excretion and CKD Progression.

    Science.gov (United States)

    He, Jiang; Mills, Katherine T; Appel, Lawrence J; Yang, Wei; Chen, Jing; Lee, Belinda T; Rosas, Sylvia E; Porter, Anna; Makos, Gail; Weir, Matthew R; Hamm, L Lee; Kusek, John W

    2016-04-01

    CKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.

  8. Carnitine ester excretion in pediatric patients receiving parenteral nutrition.

    Science.gov (United States)

    Schmidt-Sommerfeld, E; Penn, D; Bieber, L L; Kerner, J; Rossi, T M; Lebenthal, E

    1990-08-01

    Carnitine plasma concentrations and the excretion of carnitine and individual carnitine esters were determined in 25 children and adolescents with gastrointestinal diseases receiving carnitine-free parenteral nutrition for at least 1 mo using radiochemical and radioisotopic exchange HPLC methods. Children less than 12-y-old usually had carnitine plasma concentrations less than -2 SD from the normal mean for age, whereas patients greater than 12-y-old had carnitine plasma concentrations within the normal range. Age was the only variable to correlate significantly with plasma carnitine concentrations during parenteral nutrition. Free carnitine (FC) excretion was closely correlated with plasma FC concentrations and minimal at values less than 25 mumols/L. The excretion of FC and short-chain acylcarnitines was reduced by an order of magnitude in younger compared with older patients and controls, but the excretion of "other" acylcarnitines was less affected. Some of the latter were tentatively identified using gas-liquid chromatographic and mass spectroscopic techniques as unsaturated and/or branched medium-chain carnitine esters with a carbon chain of C8-C10. The results suggest that FC and short-chain acylcarnitine are conserved by the kidney in nutritional carnitine deficiency but that there may be an obligatory renal excretion of other carnitine esters that contributes to the development of hypocarnitinemia in the younger age group.

  9. The Relationship of hURAT1,SLC2A9 and ABCG2 with Hyperuricemia and Gout and the Clinical Significance%hURAT1、SLC2A9、ABCG2与高尿酸血症、痛风的关系及临床意义

    Institute of Scientific and Technical Information of China (English)

    张蓓

    2013-01-01

    Hyperuricemia and gout incidence are increased steadily year by year and they have strong relationship with renal and cerebrovascular system diseases,which are drawing wide attention gradually. Recent studies have shown that genovariation of hURAT1, SLC2A9 and ABCG2 are highly correlated with hyperuricemia and gout,playing very important roles in the pathogenesis of the diseasess. Here is to make a review on the relationship between the susceptible genes and hyperuricemia and gout,and their clinical significance.%高尿酸血症和痛风与肾脏和心脑血管系统疾病的发生、发展关系密切,近年来发病率呈逐年升高趋势,逐渐引起人们的广泛重视.最近研究发现人尿酸盐转运蛋白1(hURAT1)、尿酸转运子SLC2A9和ABC转运蛋白2 (ABCG2)三个尿酸盐转运蛋白的基因变异与高尿酸血症和痛风的发生呈高度相关,在疾病发病机制中起到重要的作用.现就hURAT1、SLC2A9和ABCG2与高尿酸血症、痛风的关系及其临床意义进行综述.

  10. Diffuse FDG renal uptake in lymphoma.

    Science.gov (United States)

    Navalkissoor, Shaunak; Szyszko, Teresa; Gnanasegaran, Gopinath; Nunan, Thomas

    2010-10-01

    In patients presenting with acute renal failure and known/suspected lymphoma, the diagnosis of diffuse renal involvement is important, as there is potential for rapid resolution with chemotherapy. Although FDG is excreted through the kidneys and focal renal disease may be difficult to identify, diffuse renal FDG is more easily recognized and is always abnormal. We report a patient presenting with acute renal failure and suspected lymphoma. F-18 FDG PET/CT study demonstrated diffuse increased FDG uptake in bilaterally enlarged kidneys. Following 1 cycle of chemotherapy, the renal function normalized. An interim F-18 FDG PET/CT demonstrated normal size and FDG uptake within both kidneys.

  11. Application of 99mTc-DTPA Radiotracer in Persian Cat's Renal ...

    African Journals Online (AJOL)

    renal organ. dministration of the radioisotope and accumulation of ... cat's renal scintigraphy, and this makes it potentially useful in research and ... system, this compound is excreted by the ... studies from animal and environment were done.

  12. 1!Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease

    Science.gov (United States)

    Schwarzschild, Michael A.; Schwid, Steven R.; Marek, Kenneth; Watts, Arthur; Lang, Anthony E.; Oakes, David; Shoulson, Ira; Ascherio, Alberto

    2008-01-01

    Context Prospective epidemiological studies consistently indicate that Parkinson’s disease (PD) risk declines with increasing serum urate. Objective To determine whether serum urate, a purine metabolite and potent antioxidant, predicts prognosis in PD. Design, Setting, and Participants Prospective study among 804 subjects with early PD enrolled in the PRECEPT study, a clinical trial of the neuroprotectant potential of CEP-1347, conducted between April 2002 and August 2005 (average follow-up time 21.4 months). Main Outcome Measures The primary study endpoint was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching endpoint according to quintiles of baseline serum urate, adjusting for gender, age and other potential covariates. Change in striatal uptake of [123I]β-CIT, a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects. Results The adjusted HR of reaching endpoint declined with increasing baseline concentrations of urate; subjects in the top quintile reached the endpoint at only half the rate of subjects in the bottom quintile (HR=0.51; 95% CI: 0.37 to 0.72; p=0.0002). This association was markedly stronger in men (HR=0.39; 95% CI: 0.26 to 0.60; pdisease modifying therapy in PD. PMID:18413464

  13. Modulation of genetic associations with serum urate levels by body-mass-index in humans

    NARCIS (Netherlands)

    J.E. Huffman (Jennifer); E. Albrecht (Eva); A. Teumer (Alexander); M. Mangino (Massimo); K. Kapur (Karen); T. Johnson (Toby); Z. Kutalik (Zoltán); N. Pirastu (Nicola); G. Pistis (Giorgio); L.M. Lopez (Lorna); T. Haller (Toomas); P. Salo (Perttu); A. Goel (Anuj); M. Li (Man); T. Tanaka (Toshiko); A. Dehghan (Abbas); D. Ruggiero; G. Malerba (Giovanni); A.V. Smith (Albert Vernon); Nolte, I.M. (Ilja M.); L. Portas (Laura); Phipps-Green, A. (Amanda); Boteva, L. (Lora); P. Navarro (Pau); A. Johansson (Åsa); A.A. Hicks (Andrew); O. Polasek (Ozren); T. Esko (Tõnu); J. Peden (John); S.E. Harris (Sarah); D. Murgia (Daniela); Wild, S.H. (Sarah H.); A. Tenesa (Albert); A. Tin (Adrienne); E. Mihailov (Evelin); A. Grotevendt (Anne); G.K. Gislason; J. Coresh (Josef); P. d' Adamo (Pio); S. Ulivi (Shelia); P. Vollenweider (Peter); G. Waeber (Gérard); Campbell, S. (Susan); I. Kolcic (Ivana); Fisher, K. (Krista); M. Viigimaa (Margus); Metter, J.E. (Jeffrey E.); C. Masciullo (Corrado); Trabetti, E. (Elisabetta); Bombieri, C. (Cristina); R. Sorice; A. Döring (Angela); G. Reischl (Gunilla); K. Strauch (Konstantin); A. Hofman (Albert); A.G. Uitterlinden (André); M. Waldenberger (Melanie); H.E. Wichmann (Heinz Erich); G. Davies (Gail); A.J. Gow (Alan J.); Dalbeth, N. (Nicola); Stamp, L. (Lisa); Smit, J.H. (Johannes H.); M. Kirin (Mirna); R. Nagaraja (Ramaiah); M. Nauck (Matthias); C. Schurmann (Claudia); K. Budde (Klemens); S.M. Farrington (Susan); E. Theodoratou (Evropi); A. Jula (Antti); V. Salomaa (Veikko); C. Sala (Cinzia); C. Hengstenberg (Christian); M. Burnier (Michel); Mägi, R. (Reedik); N. Klopp (Norman); S. Kloiber (Stefan); S. Schipf (Sabine); S. Ripatti (Samuli); Cabras, S. (Stefano); N. Soranzo (Nicole); G. Homuth (Georg); T. Nutile; P. Munroe (Patricia); N. Hastie (Nick); H. Campbell (H.); I. Rudan (Igor); Cabrera, C. (Claudia); Haley, C. (Chris); O.H. Franco (Oscar); Merriman, T.R. (Tony R.); V. Gudnason (Vilmundur); M. Pirastu (Mario); B.W.J.H. Penninx (Brenda); H. Snieder (Harold); A. Metspalu (Andres); M. Ciullo; P.P. Pramstaller (Peter Paul); C.M. van Duijn (Cock); L. Ferrucci (Luigi); G. Gambaro (Giovanni); Deary, I.J. (Ian J.); M.G. Dunlop (Malcolm); J.F. Wilson (James F); P. Gasparini (Paolo); U. Gyllensten (Ulf); T.D. Spector (Timothy); A.F. Wright (Alan); C. Hayward (Caroline); H. Watkins (Hugh); M. Perola (Markus); M. Bochud (Murielle); W.H.L. Kao (Wen); M. Caulfield (Mark); D. Toniolo (Daniela); H. Völzke (Henry); C. Gieger (Christian); A. Köttgen (Anna); V. Vitart (Veronique)

    2015-01-01

    textabstractWe tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in

  14. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

    NARCIS (Netherlands)

    Huffman, Jennifer E.; Albrecht, Eva; Teumer, Alexander; Mangino, Massimo; Kapur, Karen; Johnson, Toby; Kutalik, Zoltn; Pirastu, Nicola; Pistis, Giorgio; Lopez, Lorna M.; Haller, Toomas; Salo, Perttu; Goel, Anuj; Li, Man; Tanaka, Toshiko; Dehghan, Abbas; Ruggiero, Daniela; Malerba, Giovanni; Smith, Albert V.; Nolte, Ilja M.; Portas, Laura; Phipps-Green, Amanda; Boteva, Lora; Navarro, Pau; Johansson, Asa; Hicks, Andrew A.; Polasek, Ozren; Esko, Tonu; Peden, John F.; Harris, Sarah E.; Murgia, Federico; Wild, Sarah H.; Tenesa, Albert; Tin, Adrienne; Mihailov, Evelin; Grotevendt, Anne; Gislason, Gauti K.; Coresh, Josef; D'Adamo, Pio; Ulivi, Sheila; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Kolcic, Ivana; Fisher, Krista; Viigimaa, Margus; Metter, Jeffrey E.; Masciullo, Corrado; Trabetti, Elisabetta; Bombieri, Cristina; Sorice, Rossella; Doering, Angela; Reischl, Eva; Strauch, Konstantin; Hofman, Albert; Uitterlinden, Andre G.; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J.; Dalbeth, Nicola; Stamp, Lisa; Smit, Johannes H.; Kirin, Mirna; Nagaraja, Ramaiah; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Farrington, Susan M.; Theodoratou, Evropi; Jula, Antti; Salomaa, Veikko; Sala, Cinzia; Hengstenberg, Christian; Burnier, Michel; Maegi, Reedik; Klopp, Norman; Kloiber, Stefan; Schipf, Sabine; Ripatti, Samuli; Cabras, Stefano; Soranzo, Nicole; Homuth, Georg; Nutile, Teresa; Munroe, Patricia B.; Hastie, Nicholas; Campbell, Harry; Rudan, Igor; Cabrera, Claudia; Haley, Chris; Franco, Oscar H.; Merriman, Tony R.; Gudnason, Vilmundur; Pirastu, Mario; Penninx, Brenda W.; Snieder, Harold; Metspalu, Andres; Ciullo, Marina; Pramstaller, Peter P.; van Duijn, Cornelia M.; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J.; Dunlop, Malcolm G.; Wilson, James F.; Gasparini, Paolo; Gyllensten, Ulf; Spector, Tim D.; Wright, Alan F.; Hayward, Caroline; Watkins, Hugh; Perola, Markus; Bochud, Murielle; Kao, W. H. Linda; Caulfield, Mark; Toniolo, Daniela; Voelzke, Henry; Gieger, Christian; Koettgen, Anna; Vitart, Veronique

    2015-01-01

    We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-s

  15. PENGARUH PEMBERIAN AIR REBUSAN DAUN SALAM (SYZYGIUM POLYANTHUM TERHADAP PENURUNAN KADAR ASAM URAT

    Directory of Open Access Journals (Sweden)

    Aidaa Andriani

    2016-05-01

    Full Text Available Gout is a disease because of abnormalities purine metabolism (hyperuricemia. In gout treatment there are many different ways to lower uric acid levels one by utilizing existing natural vegetation. Plants or plants that can be used is the bay leaf (Syzygium polyanthum. Bay leaf contains flavonoids that can lower uric acid levels. This study intends to find out The Effect Of Water Decoction Bay Leaf (Syzygium polyanthum The Decrease Uric Acid Levels In The Work Area Health Center Paninggahan Solok 2013.This research is the method of approach Preeksperimental pretest - posttest, using total sampling method with a sample size of 10 people. The data was collected directly to the respondents by interview, observation and measurement sheet uric acid levels and blood sugar.The research found that there are differences in uric acid levels before and after giving the water decoction bay leaf. Based on the result test T there are differences in uric acid levels before and after giving the water decoction of bay leaf. Where the average uric acid levels before was 7.16 mg / dl, and after the uric acid level was 5.76 mg / dl. Then obtained p value = 0.000. Based on the results of this study concluded that consuming the water decoction of bay leaf can lower uric acid levels, because leaves contains flavanoid . For that gout sufferers is recommended to consume the water decoction of bay leaf  to control uric acid levels in the body. it is required to research more about the side effects and benefits of bay leaf.Penyakit asam urat merupakan suatu penyakit karena kelainan metabolisme purin (hiperurisemia. Untuk menurunkan kadar asam urat salah satunya dengan memanfaatkan tumbuhan alami yang ada. Tumbuhan atau tanaman yang dapat digunakan adalah daun salam. Daun salam memiliki kandungan flavonoid yang mampu menurunkan kadar asam urat. Penelitian ini bertujuan untuk mengetahui adanya Pengaruh Pemberian Air Rebusan Daun Salam Terhadap Penurunan Kadar Asam Urat

  16. Modulation of genetic associations with serum urate levels by body-mass-index in humans.

    Science.gov (United States)

    Huffman, Jennifer E; Albrecht, Eva; Teumer, Alexander; Mangino, Massimo; Kapur, Karen; Johnson, Toby; Kutalik, Zoltán; Pirastu, Nicola; Pistis, Giorgio; Lopez, Lorna M; Haller, Toomas; Salo, Perttu; Goel, Anuj; Li, Man; Tanaka, Toshiko; Dehghan, Abbas; Ruggiero, Daniela; Malerba, Giovanni; Smith, Albert V; Nolte, Ilja M; Portas, Laura; Phipps-Green, Amanda; Boteva, Lora; Navarro, Pau; Johansson, Asa; Hicks, Andrew A; Polasek, Ozren; Esko, Tõnu; Peden, John F; Harris, Sarah E; Murgia, Federico; Wild, Sarah H; Tenesa, Albert; Tin, Adrienne; Mihailov, Evelin; Grotevendt, Anne; Gislason, Gauti K; Coresh, Josef; D'Adamo, Pio; Ulivi, Sheila; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Kolcic, Ivana; Fisher, Krista; Viigimaa, Margus; Metter, Jeffrey E; Masciullo, Corrado; Trabetti, Elisabetta; Bombieri, Cristina; Sorice, Rossella; Döring, Angela; Reischl, Eva; Strauch, Konstantin; Hofman, Albert; Uitterlinden, Andre G; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Dalbeth, Nicola; Stamp, Lisa; Smit, Johannes H; Kirin, Mirna; Nagaraja, Ramaiah; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Farrington, Susan M; Theodoratou, Evropi; Jula, Antti; Salomaa, Veikko; Sala, Cinzia; Hengstenberg, Christian; Burnier, Michel; Mägi, Reedik; Klopp, Norman; Kloiber, Stefan; Schipf, Sabine; Ripatti, Samuli; Cabras, Stefano; Soranzo, Nicole; Homuth, Georg; Nutile, Teresa; Munroe, Patricia B; Hastie, Nicholas; Campbell, Harry; Rudan, Igor; Cabrera, Claudia; Haley, Chris; Franco, Oscar H; Merriman, Tony R; Gudnason, Vilmundur; Pirastu, Mario; Penninx, Brenda W; Snieder, Harold; Metspalu, Andres; Ciullo, Marina; Pramstaller, Peter P; van Duijn, Cornelia M; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Dunlop, Malcolm G; Wilson, James F; Gasparini, Paolo; Gyllensten, Ulf; Spector, Tim D; Wright, Alan F; Hayward, Caroline; Watkins, Hugh; Perola, Markus; Bochud, Murielle; Kao, W H Linda; Caulfield, Mark; Toniolo, Daniela; Völzke, Henry; Gieger, Christian; Köttgen, Anna; Vitart, Veronique

    2015-01-01

    We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

  17. Modulation of genetic associations with serum urate levels by body-mass-index in humans.

    Directory of Open Access Journals (Sweden)

    Jennifer E Huffman

    Full Text Available We tested for interactions between body mass index (BMI and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8. Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8, a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8, regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4. Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

  18. VizieR Online Data Catalog: URAT Parallax Catalog (UPC) (Finch+, 2016)

    Science.gov (United States)

    Finch, C. T.; Zacharias, N.

    2016-04-01

    The URAT Parallax Catalog (UPC) consists of 112177 parallaxes. The catalog utilizes all Northern Hemisphere epoch data from the United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT). This data includes all individual exposures from April 2012 to June 2015 giving a larger epoch baseline for determining parallaxes over the 2-year span of the First USNO Robotic Astrometric Telescope Catalog (URAT1) (Zacharias et al., 2015, Cat. I/329) published data. The URAT parallax pipeline is custom code that utilizes routines from (Jao, C.-W., 2004, PhD thesis Georgia Stat), the JPL DE405 ephemeris and Green's parallax factor (Green, R.M., 1985, Spherical Astronomy) for determining parallaxes from a weighted least-squares reduction. The relative parallaxes have been corrected to absolute by using the distance color relation described in (Finch et. al, 2014, Cat. J/AJ/148/119) to determine a mean distance of all UCAC4 reference stars (R=8-16 mag) used in the astrometric reductions. Presented here are all significant parallaxes from the URAT Northern Hemisphere epoch data comprising of 2 groups: a) URAT parallax results for stars with prior published parallax, and b) first time trigonometric parallaxes as obtained from URAT data of stars without prior published parallax. Note, more stringent selection criteria have been applied to the second group than the first in order to keep the rate of false detections low. For specific information about the astrometric reductions please see 'The First U.S. Naval Observatory Robotic Astrometric Telescope Catalog' published paper (Zacharias et al., 2015AJ....150..101Z, Cat. I/329). For complete details regarding the parallax pipeline please see 'Parallax Results From URAT Epoch Data' (Finch and Zacharias, 2016, AJ, in press). This catalog gives all positions on the ICRS at Epoch J2014.0; it covers the magnitude range 6.56 to 16.93 in the URAT band-pass, with an average parallax precision of 4.3mas for stars having no known

  19. Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

    Science.gov (United States)

    Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

    1980-08-01

    1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic

  20. Purine-induced expression of urate oxidase and enzyme activity in Atlantic salmon (Salmo salar). Cloning of urate oxidase liver cDNA from three teleost species and the African lungfish Protopterus annectens.

    Science.gov (United States)

    Andersen, Øivind; Aas, Turid S; Skugor, Stanko; Takle, Harald; van Nes, Solveig; Grisdale-Helland, Barbara; Helland, Ståle J; Terjesen, Bendik F

    2006-07-01

    The peroxisomal enzyme urate oxidase plays a pivotal role in the degradation of purines in both prokaryotes and eukaryotes. However, knowledge about the purine-induced expression of the encoding gene is lacking in vertebrates. These are the first published sequences of fish urate oxidase, which were predicted from PCR amplified liver cDNAs of Atlantic salmon (Salmo salar), Atlantic cod (Gadus morhua), Atlantic halibut (Hippoglossus hippoglossus) and African lungfish (Protopterus annectens). Sequence alignment of different vertebrate urate oxidases revealed amino acid substitutions of putative functional importance in the enzyme of chicken and lungfish. In the adult salmon, expression of urate oxidase mRNA predominated in liver, but was also identified in several nonhepatic organs including brain, but not in skeletal muscle and kidney. Juvenile salmon fed diets containing bacterial protein meal (BPM) rich in nucleic acids showed a significant increase in liver urate oxidase enzyme activity, and urea concentrations in plasma, muscle and liver were elevated. Whereas salmon fed the 18% BPM diet showed a nonsignificant increase in liver mRNA levels of urate oxidase compared with the 0% BPM-fed fish, no further increase in mRNA levels was found in fish receiving 36% BPM. The discrepancy between urate oxidase mRNA and enzyme activity was explained by rapid mRNA degradation or alternatively, post-translational control of the activity. Although variable plasma and liver levels of urate were detected, the substrate increased only slightly in 36% BPM-fed fish, indicating that the uricolytic pathway of Atlantic salmon is intimately regulated to handle high dietary purine levels.

  1. Correction: Absolute stereochemistry and preferred conformations of urate degradation intermediates from computed and experimental circular dichroism spectra.

    Science.gov (United States)

    Pipolo, Silvio; Percudani, Riccardo; Cammi, Roberto

    2016-04-14

    Correction for 'Absolute stereochemistry and preferred conformations of urate degradation intermediates from computed and experimental circular dichroism spectra' by Silvio Pipolo et al., Org. Biomol. Chem., 2011, 9, 5149-5155.

  2. Urinary sulphate excretion and progression of diabetic nephropathy in Type1 diabetes

    NARCIS (Netherlands)

    Andresdottir, G.; Bakker, S. J. L.; Hansen, H. P.; Parving, H-H; Rossing, P.

    Aims Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy. Methods We conducted a post-hoc study

  3. Water immersion is associated with an increase in aquaporin-2 excretion in healthy volunteers.

    NARCIS (Netherlands)

    Valenti, G.; Fraszl, W.; Addabbo, F.; Tamma, G.; Procino, G.; Satta, E.; Cirillo, M.; Santo, N.G. De; Drummer, C.; Bellini, L.; Kowoll, R.; Schlemmer, M.; Vogler, S.; Kirsch, K.A.; Svelto, M.; Gunga, H.C.

    2006-01-01

    Here, we report the alterations in renal water handling in healthy volunteers during a 6 h thermoneutral water immersion at 34 to 36 degrees C. We found that water immersion is associated with a reversible increase in total urinary AQP2 excretion.

  4. What predicts progression and regression of urinary albumin excretion in the nondiabetic population?

    NARCIS (Netherlands)

    Brantsma, Auke H.; Atthobari, Jarir; Bakker, Stephan J. L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

    2007-01-01

    An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondi

  5. Urinary sulphate excretion and progression of diabetic nephropathy in Type1 diabetes

    NARCIS (Netherlands)

    Andresdottir, G.; Bakker, S. J. L.; Hansen, H. P.; Parving, H-H; Rossing, P.

    2013-01-01

    Aims Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy. Methods We conducted a post-hoc study

  6. Effect of diethyl ether on the biliary excretion of acetaminophen.

    Science.gov (United States)

    Watkins, J B; Siegers, C P; Klaassen, C D

    1984-10-01

    The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic

  7. Pengaruh Pemberian Kopi Instan Oral Terhadap Kadar Asam Urat pada Tikus Wistar

    Directory of Open Access Journals (Sweden)

    Fauzan Arisyi Koto

    2014-09-01

    Full Text Available AbstrakKopi merupakan salah satu minuman yang paling banyak dikonsumsi di dunia. Banyak studi yang meneliti efek konsumsi kopi terhadap berbagai kondisi medis tertentu. Salah satu efek dari kopi yang masih menjadi kontroversi adalah efek terhadap penurunan kadar asam urat. Kandungan polifenol dalam kopi diduga dapat menghambat kerja xantin oksidase sehingga menurunkan kadar asam urat. Tujuan penelitian ini adalah untuk menentukan pengaruh pemberian kopi oral terhadap kadar asam urat serum pada tikus wistar. Ini adalah penelitian eksperimental dengan rancangan post test only control group design. Sampel penelitian adalah 24 ekor tikus putih jantan (Rattus novergicus yang dibagi menjadi 4 kelompok yaitu kelompok kontrol, perlakuan 1, perlakuan 2 dan perlakuan 3. Kontrol hanya diberi diet standar tanpa kopi, perlakuan 1diberikan diet kopi dosis rendah setara 3 cangkir kopi (0,39 mg/3 ml, perlakuan 2 diberikan diet kopi dosis sedang setara 6 cangkir kopi (0,78 mg/ 3ml, perlakuan 3 diberikan diet kopi dosis tinggi setara 10 cangkir kopi (1,3 mg/ 3ml selama 4 minggu (28 hari. Pengukuran kadar asam urat serum menggunakan spektofotometer. Hasil penelitian didapatkan rerata kadar asam urat serum kontrol (2,26+0,16 mg/dl, perlakuan 1 (2,24+0,89 mg/dl, perlakuan 2 (1,00+0,33 mg/dl, perlakuan 3 (1,96+0,43 mg/dl. Uji analisis one way Anova dan Post hoc menunjukkan bahwa perbedaan yang bermakna hanya terdapat pada perbandingan kelompok kontrol dengan kelompok perlakuan 2 dan antara kelompok perlakuan 1 dengan kelompok perlakuan 2 (p<0,05. Kesimpulan dari penelitian ini adalah terdapat penurunan kadar asam urat serum setelah pemberian kopi dan terdapat perbedaan bermakna kadar asam urat antara kelompok kontrol dan perlakuan 1 dengan kelompok perlakuan 2.Kata kunci: kopi, polifenol, asam urat serumAbstractCoffee is one of the most frequently consumed beverages in the world. Many studies have examined the effect of coffee consumption on a wide range of specific

  8. [Uricosuric agent].

    Science.gov (United States)

    Ohno, Iwao

    2008-04-01

    Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.

  9. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    DEFF Research Database (Denmark)

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...

  10. Urinary albumin excretion. An independent predictor of ischemic heart disease

    DEFF Research Database (Denmark)

    Borch-Johnsen, K; Feldt-Rasmussen, B; Strandgaard, S

    1999-01-01

    ischemic heart disease (IHD) in a population-based cohort. In 1983, urinary albumin and creatinine levels were measured, along with the conventional atherosclerotic risk factors, in 2085 consecutive participants without IHD, renal disease, urinary tract infection, or diabetes mellitus. The participants......Cross-sectional studies suggest that an increased urinary albumin excretion rate is associated with cardiovascular disease, dyslipidemia, and hypertension. The purpose of this study was to analyze prospectively whether the urinary albumin-to -creatinine (A/C) ratio can independently predict......, 1.3 to 3.9, P=0.002), and the 10-year disease-free survival decreased from 97% to 91% (P

  11. Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved.

    Science.gov (United States)

    Thiele, Ralf G; Schlesinger, Naomi

    2010-02-01

    This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain < or =6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.

  12. Application of pharmacokinetics local model to evaluate renal function

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The pharmacokinetics local model was used to evaluate renal function.Some typical kinds of renal function cases, normal or disorder, were selected to be imaged with SPECT and those data measured were treated by the pharmacokinetics local model computer program (PLM).The results indicated that parameters, including peak value, peak time, inflexion time, half-excretion time, and kinetic equation played and importantrole in judging renal function.The fact confirms that local model isvery useful in evaluating renal function.

  13. Competition by meperidine for the organic cation renal excretory system.

    Science.gov (United States)

    Acara, M; Gessner, T; Trudnowski, R J

    1981-07-01

    Renal tubular excretory transport of meperidine was studied using the Sperber preparation in chickens. When urine samples from infused and uninfused kidneys were analyzed for meperidine by gas chromatography, meperidine was always present in greater amounts in the urine from the infused kidney, demonstrating active tubular excretion. Meperidine at an infusion rate of 1 mumole/min, also inhibited the excretion of the organic cations choline and acetylcholine, indicating occupation of the renal organic cation excretory system in the chicken.

  14. Cholesterol excretion and colon cancer.

    Science.gov (United States)

    Broitman, S A

    1981-09-01

    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  15. Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia.

    Science.gov (United States)

    Wang, Yu; Lin, Zhijian; Zhang, Bing; Nie, Anzheng; Bian, Meng

    2017-01-01

    Excessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo. Chicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed. The administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum. These findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via down-regulating the mRNA and protein expressions of ABCG2.

  16. Mechanisms of the Effects of Acidosis and Hypokalemia on Renal Ammonia Metabolism

    OpenAIRE

    Han, Ki-Hwan

    2011-01-01

    Renal ammonia metabolism is the predominant component of net acid excretion and new bicarbonate generation. Renal ammonia metabolism is regulated by acid-base balance. Both acute and chronic acid loads enhance ammonia production in the proximal tubule and secretion into the urine. In contrast, alkalosis reduces ammoniagenesis. Hypokalemia is a common electrolyte disorder that significantly increases renal ammonia production and excretion, despite causing metabolic alkalosis. Although the net ...

  17. Gastrointestinal osmoreceptors and renal sodium excretion in humans

    DEFF Research Database (Denmark)

    Andersen, L J; Skram, Thomas Ulrik; Bestle, M H;

    2000-01-01

    The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogas......The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered......-angiotensin system....

  18. Sodium loading changes urinary protein excretion: a proteomic analysis.

    Science.gov (United States)

    Thongboonkerd, Visith; Klein, Jon B; Pierce, William M; Jevans, Anthony W; Arthur, John M

    2003-06-01

    Plasma sodium concentration is maintained even when sodium intake is altered. Sodium homeostasis may involve changes in renal tubular protein expression that are reflected in the urine. We used proteomic analysis to investigate changes in urinary protein excretion in response to acute sodium loading. Rats were given deionized water followed by hypertonic (2.7%) saline for 28 h each. Urinary protein expression was determined during the final 4 h of each treatment. Acute sodium loading increased urinary sodium excretion (4.53 +/- 1.74 vs. 1.70 +/- 0.27 mmol/day, P = 0.029). Urinary proteins were separated by two-dimensional PAGE and visualized by Sypro ruby staining. Differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry followed by peptide mass fingerprinting. The abundance of a total of 45 protein components was changed after acute sodium loading. Neutral endopeptidase, solute carrier family 3, meprin 1alpha, diphor-1, chaperone heat shock protein 72, vacuolar H(+)-ATPase, ezrin, ezrin/radixin/moesin-binding protein, glutamine synthetase, guanine nucleotide-binding protein, Rho GDI-1, and chloride intracellular channel protein 1 were decreased, whereas albumin and alpha-2u globulin were increased. Some of these proteins have previously been shown to be associated with tubular transport. These data indicate that alterations in the excretion of several urinary proteins occur during acute sodium loading.

  19. Nutrition and renal disease.

    Directory of Open Access Journals (Sweden)

    Iris de Castaño

    2009-11-01

    Full Text Available Kidney plays an important roll in body homeostasis through excretory, metabolic and endocrine functions. Kidneys filter fluids and solutes and reabsorbed water , electrolytes an minerals. Urine volume and solute excretion are adjusted to keep composition of the extracellular space, serum osmolarity and intravascular volume in constant balance. Kidneys also regulate acid base equilibrium, hormone metabolism and excretion and amino acid concentration. Vitamin D hydroxylation takes place in the kidney, this is the active form of this vitamin, which inhibits PTH. In addition they produce erythropoietin which control hemoglobin concentration in erythrocytes. When renal insufficiency develops, and glormerular filtration rate is between 50 to 75% of normal, this functions are decreased .When renal function is less than 10%, this functions ceased. In children small changes in water, solute, acid base, calcium and phosphorus can alter normal growth and development. If kidneys can not maintain internal equilibrium, specific nutrients should be used. Compensation should be done according to age, type or renal disease and level of glomerular filtration rate.

  20. Impaired renal function is associated with greater urinary strong ion differences in critically ill patients with metabolic acidosis.

    NARCIS (Netherlands)

    Moviat, M.; Terpstra, A.M.; Hoeven, J.G. van der; Pickkers, P.

    2012-01-01

    PURPOSE: Urinary excretion of chloride corrects metabolic acidosis, but this may be hampered in patients with impaired renal function. We explored the effects of renal function on acid-base characteristics and urinary strong ion excretion using the Stewart approach in critically ill patients with me

  1. Essential trace metal excretion from rats with lead exposure and during chelation therapy.

    Science.gov (United States)

    Victery, W; Miller, C R; Goyer, R A

    1986-02-01

    Urinary excretion of lead, zinc, calcium, magnesium, iron, copper, sodium, and potassium was measured in rats daily for 1 week after a 6-week exposure to 10,000 micrograms/ml lead in drinking water. Beginning on the third day, half of the lead-exposed and control rats were injected intraperitoneally with calcium disodium ethylenediaminetetraacetate (EDTA) daily for 3 days. Whole blood, plasma, and kidney metal concentrations were determined from samples obtained at the end of the experiment. Exposure to lead increased urinary excretion, not only of lead, but also of calcium, magnesium, zinc, copper, and iron. Excretion of sodium and potassium was not altered. Chelation therapy further increased excretion of lead, zinc, copper, and iron, but not magnesium. The increase in calcium excretion during chelation treatment (beyond that resulting from lead exposure per se) was accounted for by the Ca content of CaNa2-EDTA. EDTA treatment increased renal concentration of zinc but lowered renal concentration of lead, copper, and iron. These multimetal alterations may have implications for essential metal supplementation, particularly zinc, in persons being given chelation agents for excess lead exposure and in infants and children with low-level lead exposure not necessarily requiring chelation therapy.

  2. Clinical significance of the fractional excretion of anions in metabolic acidosis.

    Science.gov (United States)

    Kim, H Y; Han, J S; Jeon, U S; Joo, K W; Earm, J H; Ahn, C; Kim, S; Lee, J S; Kim, G H

    2001-06-01

    The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p anions may provide a useful clue to the differential diagnosis of metabolic acidosis caused by acid overproduction.

  3. Transient renal dysfunction with reversible splenial lesion.

    Science.gov (United States)

    Watanabe, Toru; Matsuda, Tomoka; Kitagata, Ryoichi; Tajima, Iwao; Ono, Hiroyuki; Hirano, Keiko; Shirai, Masami; Endoh, Akira; Hongo, Teruaki

    2014-10-01

    We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.

  4. 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

  5. Tissular localization and excretion of intravenously administered silica nanoparticles of different sizes

    Energy Technology Data Exchange (ETDEWEB)

    Xie Guangping; Sun Jiao, E-mail: jiaosun59@yahoo.com [Shanghai Jiaotong University School of Medicine, Shanghai Biomaterials Research and Testing Center, Shanghai Ninth People' s Hospital (China); Zhong Gaoren [Fudan University, School of Pharmacy (China)

    2012-01-15

    The nanotoxicology as a new subdiscipline of nanotechnology needs to be studied in vivo. To do so, it is essential to understand certain pharmacological information of the nanoparticles in vivo. Silica nanoparticles (SiNPs) have been developed for a number of biomedical uses; however, research on their tissular localization and excretion has been limited. In this study, we analyzed the localization of intravenously administered SiNPs with sizes of 20 and 80 nm in liver and spleen and quantitatively investigated the excretion of SiNPs through urine and feces. The results of the tissular localization study showed that the SiNPs were located in liver evenly; however, they were mainly accumulated in the white pulp of spleen. The quantitative excretory assay found the renal excretion being the main excretion pathway of SiNPs and indicated that the accumulated excretory rate of 80 nm SiNPs through urine was higher than that of 20 nm SiNPs because of the higher hemoconcentration. Further analysis of radioactive substances in the excreta showed the convincing confirmatory evidence that the SiNPs of both the sizes of 20 and 80 nm could be excreted through urine. These results provide important information on in vivo distribution and excretion of SiNPs.

  6. Taurine and the renal system

    Science.gov (United States)

    2010-01-01

    Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed. PMID:20804616

  7. THE RENAL HANDLING OF HEMOGLOBIN

    Science.gov (United States)

    Bunn, H. Franklin; Esham, William T.; Bull, Robert W.

    1969-01-01

    The glomerular filtration of hemoglobin (α2β2) was studied under conditions in which its dissociation into αβ dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of 59Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose. PMID:5778789

  8. Inhibition of Monosodium Urate Monohydrate-mediated Hemolysis by Vitamin E

    Institute of Scientific and Technical Information of China (English)

    Qiong XIE; Shude LI; Weiyang FENG; Yongzhi LI; Yuanliang WU; Wei HU; Youguang HUANG

    2007-01-01

    Microcrystals of monosodium urate monohydrate (MSUM) induce cytolysis and hemolysis in erythrocytes. In this report, we studied the effect of vitamin E on MSUM-mediated hemolysis in human erythrocytes. Vitamin E significantly inhibited hemolysis induced by MSUM. The hydroxyl group in the chromanol ring of vitamin E is dispensable for protecting erythrocytes against hemolysis induced by MSUM,indicating that the inhibitory effect of vitamin E is not due to its antioxidant properties. However, both the chromanol ring and the isoprenoid side chain are important for vitamin E to suppress MSUM-induced hemolysis.Our current study suggests that vitamin E inhibits hemolysis induced by MSUM as a membrane stabilizer.

  9. 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, ...

  10. Effect of water deprivation, desmopressin (DDAVP) infusion, and oral loads of water, Na+ and NH4+ on urinary excretion of epidermal growth factor in the rat

    DEFF Research Database (Denmark)

    Jørgensen, P E; Poulsen, Steen Seier; Nexø, Ebba

    1993-01-01

    Epidermal growth factor (EGF) is synthesized in the kidneys and excreted in urine. Administration of exogenous EGF modulates the reabsorption of Na+ and the vasopressin stimulated reabsorption of water in the collecting tubules. In order to clarify whether this reflects a physiological role...... for urinary EGF we examined the effects of changes in the oral loads of water, Na+ and NH4+ as well as the effect of infusion of the vasopressin analogue, desmopressin (DDAVP) on the endogenous urinary EGF excretion in the rat. Water deprivation for 48 h reduced the urinary excretion of EGF by 25......% and the urinary EGF/creatinine ratio by 8%. Also, urinary volume, Na+ excretion, and urinary pH were reduced by water deprivation. Infusion of DDAVP, low plasma vasopressin induced by polydipsia, and changes in the renal excretion of Na+ and H+ did not affect the urinary excretion of EGF. In conclusion: it seems...

  11. Role of vascular potassium channels in the regulation of renal hemodynamics

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik

    2012-01-01

    of one or more classes of K+ channels will lead to a change in hemodynamic resistance and therefore of renal blood flow and glomerular filtration pressure. Through these effects, the activity of renal vascular K+ channels influences renal salt and water excretion, fluid homeostasis, and ultimately blood...

  12. [The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

    Science.gov (United States)

    Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

    2012-04-01

    During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen

  13. Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects.

    Science.gov (United States)

    Han, Jieru; Xie, Ying; Sui, Fangyu; Liu, Chunhong; Du, Xiaowei; Liu, Chenggang; Feng, Xiaoling; Jiang, Deyou

    2016-09-01

    Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal‑induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine‑rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor‑α and interleukin‑1β, and inhibited activation of nuclear factor‑κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal‑induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti‑oxidative and anti‑inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis.

  14. Urate Oxidase Knockdown Decreases Oxidative Stress in a Murine Hepatic Cell Line

    Directory of Open Access Journals (Sweden)

    Beth M. Cleveland

    2009-01-01

    Full Text Available Humans, birds, and some primates do not express the uric acid degrading enzyme urate oxidase (UOX and, as a result, have plasma uric acid concentrations higher than UOX expressing animals. Although high uric acid concentrations are suggested to increase the antioxidant defense system and provide a health advantage to animals without UOX, knockout mice lacking UOX develop pathological complications including gout and kidney failure. As an alternative to the knockout model, RNA interference was used to decrease UOX expression using stable transfection in a mouse hepatic cell line (ATCC, FL83B. Urate oxidase mRNA was reduced 66% (p < 0.05 compared to wild type, as measured by real time RT-PCR. To determine if UOX knockdown resulted in enhanced protection against oxidative stress, cells were challenged with hexavalent chromium (Cr(VI or 3-morpholinosydnonimine hydrochloride (SIN-1. Compared to wild type, cells with UOX knockdown exhibited a 37.2 ± 3.5% reduction (p < 0.05 in the electron spin resonance (ESR signal after being exposed to Cr(VI and displayed less DNA fragmentation (p < 0.05 following SIN-1 treatment. Cell viability decreased in wild type cells (p < 0.05, but not cells with UOX knockdown, after treatment with SIN-1. These results are consistent with an increased intracellular uric acid concentration and an increased defense against oxidative stress.

  15. Urate crystal degradation for treatment of gout: a nanoparticulate combination therapy approach.

    Science.gov (United States)

    Tiwari, Sanjay; Dwivedi, Harinath; Kymonil, Koshy M; Saraf, Shubhini A

    2015-06-01

    The objective of the present work was to develop polymeric nanoparticles of uricase and aceclofenac (NSAID) and to incorporate them into gel, for delivering drugs to synovial joints, for effective treatment of Gout. Nanoparticles containing uricase and aceclofenac were prepared by double emulsion solvent evaporation method and emulsion solvent evaporation, using PLGA (50:50) as carrier, respectively. Process parameters were optimized using Taguchi L4 orthogonal array and L9 array, respectively. The formulations were characterized for particle size, entrapment efficiency, surface charge, in vitro drug release, ex vivo drug permeation, and urate crystal degradation activity. The particle size and entrapment efficiency for optimized batch was found to be 228.8 nm and 81.26% for uricase nanoparticles and 288.5 nm and 85.36% for aceclofenac nanoparticles, respectively. The developed nanoparticles formulations displayed zero order and Higuchi release kinetics with non-Fickian diffusion, respectively. The in vivo studies were performed in rabbit model. Topical application of gel containing polymeric uricase nanoparticles alone and a combination of both, uricase nanoparticles and aceclofenac nanoparticles in rabbit model test groups, provided complete removal of urate crystals and inflammation within 40 and 25 days of treatment, respectively. The combination treatment therapy resulted in effective treatment of gout due to degradation of crystals and anti-inflammatory response.

  16. Synergism between maggot excretions and antibiotics.

    Science.gov (United States)

    Cazander, Gwendolyn; Pawiroredjo, Janity S; Vandenbroucke-Grauls, Christina M J E; Schreurs, Marco W J; Jukema, Gerrolt N

    2010-01-01

    Maggots are successfully used to treat severe, infected wounds. This study investigated whether maggot excretions/secretions influence the antibacterial activity of different antibiotics. Minimal inhibitory concentrations and minimal bactericidal concentrations (MBC) were determined of gentamicin and flucloxacillin for Staphylococcus aureus, of penicillin for Streptococcus pyogenes, of amoxicillin and vancomycin for Enterococcus faecalis, of gentamicin for Enterobacter cloacae, and of gentamicin, tobramycin, and ciprofloxacin for Pseudomonas aeruginosa by checkerboard titration. A range of concentrations of antibiotics in combination with excretions/secretions was examined to investigate the potential of maggot excretions/secretions to affect antibacterial activity. The results showed a dose-dependent increase of the antibacterial effect of gentamicin in the presence of excretions/secretions on S. aureus. Minimal concentrations and MBC of gentamicin decreased, respectively, 64- and 32-fold. The MBC of flucloxacillin and excretions/secretions against S. aureus were also decreased. The other antibiotic and excretions/secretions combinations exerted an indifferent effect. Excretions/secretions alone did not have any antibacterial effect. The synergism between gentamicin and maggot excretions/secretions could be of direct importance in clinical practice, because it could allow the use of lower doses of gentamicin and thus minimize the risk of gentamicin-related side effects.

  17. Iodine excretion in school children in Copenhagen

    DEFF Research Database (Denmark)

    Rasmussen, Lone B; Kirkegaard-Klitbo, Ditte Marie; Laurberg, Peter

    2016-01-01

    INTRODUCTION: Studies of dietary habits show a high iodine intake in children in Denmark. Iodine excretion in children has not previously been assessed. Iodine excretion in adults is below the recommended threshold, and it is therefore being discussed to increase the fortification level. The main...

  18. Cardiovascular and renal effects of hyperuricaemia and gout

    Directory of Open Access Journals (Sweden)

    R. Pontremoli

    2012-01-01

    Full Text Available A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.

  19. Renal and sympathoadrenal responses in space

    DEFF Research Database (Denmark)

    Christensen, N J; Drummer, C; Norsk, P

    2001-01-01

    According to a classic hypothesis, weightlessness should promote the renal excretion rate of sodium and water and lead to a fluid- and electrolyte-depleted state. This hypothesis is based on experiments in which weightlessness has been simulated in humans by head-down bed rest and water immersion....... However, after 5 to 6 days of space mission, the diuretic and natriuretic responses to an intravenous isotonic saline load were attenuated and plasma norepinephrine and renin concentrations increased compared with those of the acute supine position before flight. Renal fluid excretion after an oral water...... activity is increased during space flights as measured using plasma concentration and urinary excretion of norepinephrine and epinephrine. The space-induced activation of antinatriuretic mechanisms and sympathoadrenal activity could have been caused by early in-flight reduction in total and central blood...

  20. Examining the Proportion of Dietary Phosphorus From Plants, Animals, and Food Additives Excreted in Urine.

    Science.gov (United States)

    St-Jules, David E; Jagannathan, Ram; Gutekunst, Lisa; Kalantar-Zadeh, Kamyar; Sevick, Mary Ann

    2017-03-01

    Phosphorus bioavailability is an emerging topic of interest in the field of renal nutrition that has important research and clinical implications. Estimates of phosphorus bioavailability, based on digestibility, indicate that bioavailability of phosphorus increases from plants to animals to food additives. In this commentary, we examined the proportion of dietary phosphorus from plants, animals, and food additives excreted in urine from four controlled-feeding studies conducted in healthy adults and patients with chronic kidney disease. As expected, a smaller proportion of phosphorus from plant foods was excreted in urine compared to animal foods. However, contrary to expectations, phosphorus from food additives appeared to be incompletely absorbed. The apparent discrepancy between digestibility of phosphorus additives and the proportion excreted in urine suggests a need for human balance studies to determine the bioavailability of different sources of phosphorus.

  1. Mercury excretion and intravenous ascorbic acid.

    Science.gov (United States)

    Dirks, M J; Davis, D R; Cheraskin, E; Jackson, J A

    1994-01-01

    We tested the hypothesis that intravenous ascorbic acid increases urinary excretion of mercury in subjects with low mercury levels from dental amalgam, food, and other sources. From 89 adult volunteers we selected 28 subjects with the highest mercury excretions (2 to 14 micrograms/24 h). We administered intravenous infusions of 500 ml lactated Ringer's solution with and without addition of 750 mg of ascorbic acid/kg body weight, up to 60 g ascorbic acid. Average mercury excretion during the 24 h after infusion of ascorbic acid was 4.0 +/- 0.5 micrograms (mean +/- SEM), which was not significantly more than after infusion of Ringer's solution alone (3.7 +/- 0.5 micrograms). Lead excretion was similarly unaffected. If ascorbic acid administered intravenously benefits some persons with suspected adverse reactions to mercury, the benefit in subjects similar to ours appears unrelated to short-term enhanced excretion of mercury or lead.

  2. Iodine excretion in school children in Copenhagen

    DEFF Research Database (Denmark)

    Rasmussen, Lone B.; Kirkegaard-Klitbo, Ditte Marie; Laurberg, Peter

    2016-01-01

    INTRODUCTION: Studies of dietary habits show a high iodine intake in children in Denmark. Iodine excretion in children has not previously been assessed. Iodine excretion in adults is below the recommended threshold, and it is therefore being discussed to increase the fortification level. The main...... objective of this study was to assess iodine excretion in children living in Copenhagen to establish whether a moderate increase in iodine fortification would lead to excess iodine intake in this group. METHODS: Children in first and fifth grade were recruited through schools in Copenhagen. In total, 244...... children de-ivered a urine sample. Urine samples were analysed for iodine and creatinine, and the results were expressed as urinary iodine concentration (UIC) and as estimated 24-h iodine excretion. Iodine excretion in children was also compared with that of adults living in the same area, investigated...

  3. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting [v2; ref status: indexed, http://f1000r.es/1ax

    Directory of Open Access Journals (Sweden)

    Steven J Youmans

    2013-06-01

    Full Text Available We have utilized the persistent elevation of fractional excretion (FE of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW from the syndrome of inappropriate antidiuretic hormone secretion (SIADH, in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients or with SIADH (2 patients. Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future

  4. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting [v1; ref status: indexed, http://f1000r.es/nu

    Directory of Open Access Journals (Sweden)

    Steven J Youmans

    2013-05-01

    Full Text Available We have utilized the persistent elevation of fractional excretion (FE of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW from the syndrome of inappropriate antidiuretic hormone secretion (SIADH, in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients or with SIADH (2 patients. Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future

  5. Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

    Science.gov (United States)

    Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

    2017-03-01

    A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Construction of uricase-overproducing strains of Hansenula polymorpha and its application as biological recognition element in microbial urate biosensor

    Directory of Open Access Journals (Sweden)

    Schuhmann Wolfgang

    2011-05-01

    Full Text Available Abstract Background The detection and quantification of uric acid in human physiological fluids is of great importance in the diagnosis and therapy of patients suffering from a range of disorders associated with altered purine metabolism, most notably gout and hyperuricaemia. The fabrication of cheap and reliable urate-selective amperometric biosensors is a challenging task. Results A urate-selective microbial biosensor was developed using cells of the recombinant thermotolerant methylotrophic yeast Hansenula polymorpha as biorecognition element. The construction of uricase (UOX producing yeast by over-expression of the uricase gene of H. polymorpha is described. Following a preliminary screening of the transformants with increased UOX activity in permeabilized yeast cells the optimal cultivation conditions for maximal UOX yield namely a 40-fold increase in UOX activity were determined. The UOX producing cells were coupled to horseradish peroxidase and immobilized on graphite electrodes by physical entrapment behind a dialysis membrane. A high urate selectivity with a detection limit of about 8 μM was found. Conclusion A strain of H. polymorpha overproducing UOX was constructed. A cheap urate selective microbial biosensor was developed.

  7. The distribution of urate deposition within the extremities in gout: a review of 148 dual-energy CT cases

    Energy Technology Data Exchange (ETDEWEB)

    Mallinson, Paul I. [Vancouver General Hospital, Radiology Department, Vancouver (Canada); Vancouver General Hospital, Clinical Fellow in Musculoskeletal Radiology, Vancouver, BC (Canada); Reagan, Adrian C.; Munk, Peter L.; Ouellette, Hugue; Nicolaou, Savvas [Vancouver General Hospital, Radiology Department, Vancouver (Canada); Coupal, Tyler [McMaster University, De Groote School of Medicine, Hamilton, Ontario (Canada)

    2014-03-15

    Clinical detection of gout can be difficult due to co-existent and mimicking arthropathies and asymptomatic disease. Understanding of the distribution of urate within the body can aid clinical diagnosis and further understanding of the resulting pathology. Our aim was to determine this distribution of urate within the extremities in patients with gout. All patients who underwent a four-limb dual-energy computed tomography (DECT) scan for suspected gout over a 2-year period were identified (n = 148, 121 male, 27 female, age range, 16-92 years, mean = 61.3 years, median = 63 years). The reports of the positive cases were retrospectively analyzed and the locations of all urate deposition recorded and classified by anatomical location. A total of 241 cases met the inclusion criteria, of which 148 cases were positive. Of these, 101 (68.2 %) patients had gout in the foot, 81 (56.1 %) in the knee, 79 (53.4 %) in the ankle, 41 (27.7 %) in the elbow, 25 (16.9 %) in the hand, and 25 (16.9 %) in the wrist. The distribution was further subcategorized for each body part into specific bone and soft tissue structures. In this observational study, we provide for the first time a detailed analysis of extremity urate distribution in gout, which both supports and augments to the current understanding based on clinical and microscopic findings. (orig.)

  8. 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.

  9. Relationship of bone erosion with the urate and soft tissue components of the tophus in gout: a dual energy computed tomography study.

    Science.gov (United States)

    Sapsford, Mark; Gamble, Gregory D; Aati, Opetaia; Knight, Julie; Horne, Anne; Doyle, Anthony J; Dalbeth, Nicola

    2017-01-01

    Imaging and pathology studies have established a close relationship between tophus and bone erosion in gout. The tophus is an organized structure consisting of urate crystals and chronic inflammatory tissue. The aim of this work was to examine the relationship between bone erosion and each component of the tophus. Plain radiographs and dual energy CT scans of the feet were prospectively obtained from 92 people with tophaceous gout. The 10 MTP joints were scored for erosion score, tophus urate and soft tissue volume. Data were analysed using generalized estimating equations and mediation analysis. Tophus was visualized in 80.2% of all joints with radiographic (XR) erosion [odds ratio (OR) = 7.1 (95% CI: 4.8, 10.6)] and urate was visualized in 78.6% of all joints with XR erosion [OR = 6.6 (95% CI: 4.7, 9.3)]. In mediation analysis, tophus urate volume and soft tissue volume were directly associated with XR erosion score. About a third of the association of the tophus urate volume with XR erosion score was indirectly mediated through the strong association between tophus urate volume and tophus soft tissue volume. Urate and soft tissue components of the tophus are strongly and independently associated with bone erosion in gout. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. 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.

  11. [Immunohistochemical study on the mechanism of excretion of methamphetamine].

    Science.gov (United States)

    Kajitani, A; Kaiho, M; Mori, A; Okada, Y; Mukaida, M; Ishiyama, I

    1989-06-01

    Many methods of analysis are available to the forensic toxicologist for determining the amount of methamphetamine within human tissues, but few have the potential of histochemistry for enabling the precise site of excretion of methamphetamine to be defined. We have established a method for the demonstration of methamphetamine by immunohistochemistry, and applied this method for showing morphologically the disposition of methamphetamine. The following cells in the tissues of methamphetamine-intoxicated mice gave a strong positive reaction of the localization, which was thought to be the histological evidence of excretion of this drug: epithelial cells of the distal part of the renal tubule and of the collecting tubule, transitional epithelial cells of the bladder, liver parenchymal cells, epithelial cells of the striated duct of the salivary gland, parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine, secretory cells and part of epithelial cells of the ductal portion of the sweat gland, alveolar cells of the mammary gland, secretory cells of the sebaceous gland and hair medulla and cortex. These results indicated passive diffusion of methamphetamine across membranes of the cells of the distal tubule and collecting tubule of the kidney, of the bladder and of the striated duct of the salivary gland. In the parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine and secretory cells of the sweat gland, methamphetamine was thought to be stored and subsequently released. In the mammary gland, methamphetamine was found to be combined with casein and excreted by exocytosis. Accumulation of methamphetamine in the hair was supposed to be chiefly due to the penetration of this drug derived from tissue fluid and sebum.

  12. Relationship Between Changes in Serum Urate and Bone Mineral Density During Treatment with Thiazide Diuretics: Secondary Analysis from a Randomized Controlled Trial.

    Science.gov (United States)

    Dalbeth, Nicola; Gamble, Gregory D; Horne, Anne; Reid, Ian R

    2016-05-01

    In observational studies, serum urate concentrations associate with bone mineral density (BMD) and reduced risk of fractures. Thiazide diuretics slow the bone loss in healthy older adults, are associated with reduced incidence of fracture and also increase serum urate. We hypothesized that changes in serum urate are associated with changes in BMD during treatment with thiazide diuretics. We analysed data from a double-blind randomized controlled trial of hydrochlorothiazide (50 mg per day) and placebo in normal post-menopausal women. The relationship between change in serum urate and change in BMD after 2 years of treatment was examined using Spearman correlation and multiple linear regression models. Total body BMD increased in the hydrochlorothiazide group by 0.52 % and reduced in the placebo group by 0.29 % over 2 years (between group difference P = 0.0034). Serum urate increased in the hydrochlorothiazide group by 0.038 mmol/L and reduced in the placebo group by 0.004 mmol/L (between group difference P < 0.0001). At Year 2, there was a positive relationship between the change in serum urate and change in total body BMD for entire study population (r = 0.32, P = 0.0002) and for the hydrochlorothiazide group (r = 0.29, P = 0.023). The association between change in serum urate and change in total body BMD persisted after adjusting for treatment allocation, and change in weight, serum calcium, urinary calcium and serum creatinine (P change in serum urate = 0.043). These data raise the possibility that the effects of hydrochlorothiazide on BMD may be mediated, in part, by changes in serum urate concentrations.

  13. Adherence and persistence to urate-lowering therapies in the Irish setting

    LENUS (Irish Health Repository)

    McGowan, Bernie

    2014-11-01

    To identify adherence and persistence levels with urate-lowering therapies using the national administrative pharmacy claim database. This was a retrospective, pharmacy claims-based analysis of dispensed anti-gout medications on the Irish national HSE-PCRS scheme database between January 2008 and December 2012. Adherence is defined by the medication possession ratio (MPR), and patients were considered to be adherent if the MPR ≥80 % (good adherers) in any given time period. Persistence was defined as continued use of therapy with no periods exceeding a refill gap of >63 days (9 weeks). Logistic regression analysis was used to predict odd ratios (OR) and 95 % confidence interval (CI) for persistence and adherence in relation to age, gender and level of comorbidity. There was a 53 % increase in the number of patients prescribed anti-gout medications between 2008 and 2012 with an increase of 27 % in the associated ingredient cost of these medications. Allopurinol accounted for 87 % of the prescribing and febuxostat accounted for a further 9 %. In patients who started on 100 mg allopurinol, only 14.6 % were titrated to the 300 mg dose. For all those initiating urate-lowering therapies, 45.8 % of patients were persistent with treatment at 6 months decreasing to 22.6 % at 12 months. In multivariate analysis, females had poorer adherence (OR = 0.83 (0.77-0.90)), and increasing age was associated with increased adherence (OR = 4.19 (2.53-6.15)) Increasing comorbidity score was associated with increased adherence and persistence at 6 months (OR = 0.68 (0.59-0.79)). Adherence with anti-gout medications in this study cohort was relatively low. Sustained treatment for gouty arthritis is essential in the prevention of serious adverse outcomes.Significance and Innovations-Poor adherence to medications prescribed to patients for the management of chronic diseases such as gout is an ongoing problem which urgently needs to be addressed.-Some of the reasons identified

  14. Time required for disappearance of urate crystals from synovial fluid after successful hypouricaemic treatment relates to the duration of gout.

    Science.gov (United States)

    Pascual, Eliseo; Sivera, Francisca

    2007-08-01

    To determine whether hypouricaemic treatment results in the disappearance of urate crystals from gouty joints and to define the time required. In 18 patients with monosodium urate (MSU) crystal proven gout, and after the initiation of successful serum uric acid (SUA)-lowering treatment, an arthrocentesis of the asymptomatic signal joint (11 knees, 7 first metatarsophalangeal joints) was performed every 3 months to obtain a synovial fluid (SF) sample. The sample was then analysed for the presence of MSU crystals, and the number of crystals/400x field was noted. SUA levels and the duration of gout were also noted. MSU crystals disappeared from the SF of all 18 joints after reduction of SUA to normal levels. The time required for disappearance ranged from 3 to 33 months; disappearance time correlated with the duration of gout (r(s) = 0.71; pcrystals in the SF samples before urate-lowering treatment was 7.5 (2.5-11) crystals/400x field, reducing to 3 (1-6.5) crystals/400x field (pCrystal counts continued to decrease after 3 months. In gout, reduction of SUA to normal levels results in disappearance of urate crystals from SF, requiring a longer time in those patients with gout of longer duration. This indicates that urate crystal deposition in joints is reversible. Normalisation of SUA levels results in a decrease in the concentration of MSU crystals in SF in the asymptomatic gouty joints. This may partially explain the reduced frequency of gouty attacks when a patient has been treated with SUA-lowering drugs.

  15. LOW FRACTIONAL EXCRETION OF UREA IN HYPOTHYROIDISM INDUCED HYPONATREMIA

    Directory of Open Access Journals (Sweden)

    Algranati L

    2005-01-01

    Full Text Available RESUMEN:El hipotiroidismo puede causar alteraciones del metabolismo del agua, los electrolitos, la hemodinamia e histología renales, siendo la hiponatremia y la reducción del filtrado glomerular sus consecuencias más significativas, pero poco prevalentes. Todos estos cambios son corregibles con el suministro de hormona tiroidea exógena.La excreción fraccional de urea (EFU es un índice útil en la evaluación de la hiponatremia, pero no se ha descripto aun el valor que este índice alcanza en la hiponatremia inducida por hipotiroidismo. En el presente reporte mostramos que la EFU y excreción fraccional de sodio (EFNa fueron baja (EFU: 29% y alta (EFNa: 2.2% respectivamente en un paciente que padecía hipotiroideo severo. El tratamiento con hormona tiroidea normalizó el valor de ambos índices.ABSTRACTHypothyroidism can cause disturbance of renal hemodinamics, kidney histology, water and electrolyte metabolism, being hyponatremia and glomerular filtration reduction their low prevalent but most significant consequences. All these changes are largely corrected by substitution of exogenous thyroid hormone.Fractional excretion of urea (FEU is a useful index in the evaluation of hyponatremia. However, it was not still reported in the literature the FEU value in hyponatremia induced by hypothyroidism. Because of that we presented a case report showing that the value of FEU and fractional excretion of sodium (FENa were low (FEU: 29% and high (FENa: 2.2 % respectively in a severe hypothyroid patient. Treatment based on thyroid hormone normalized both indeces.

  16. Alkali absorption and citrate excretion in calcium nephrolithiasis

    Science.gov (United States)

    Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

    1993-01-01

    The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

  17. The association of dietary intake of purine-rich vegetables, sugar-sweetened beverages and dairy with plasma urate, in a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Lina Zgaga

    Full Text Available Hyperuricemia is a strong risk factor for gout. The incidence of gout and hyperuricemia has increased recently, which is thought to be, in part, due to changes in diet and lifestyle. Objective of this study was to investigate the association between plasma urate concentration and: a food items: dairy, sugar-sweetened beverages (SSB and purine-rich vegetables; b related nutrients: lactose, calcium and fructose.A total of 2,076 healthy participants (44% female from a population-based case-control study in Scotland (1999-2006 were included in this study. Dietary data was collected using a semi-quantitative food frequency questionnaire (FFQ. Nutrient intake was calculated using FFQ and composition of foods information. Urate concentration was measured in plasma.Mean urate concentration was 283.8±72.1 mmol/dL (females: 260.1±68.9 mmol/dL and males: 302.3±69.2 mmol/dL. Using multivariate regression analysis we found that dairy, calcium and lactose intakes were inversely associated with urate (p = 0.008, p = 0.003, p = 0.0007, respectively. Overall SSB consumption was positively associated with urate (p = 0.008, however, energy-adjusted fructose intake was not associated with urate (p = 0.66. The intake of purine-rich vegetables was not associated to plasma urate (p = 0.38.Our results suggest that limiting purine-rich vegetables intake for lowering plasma urate may be ineffectual, despite current recommendations. Although a positive association between plasma urate and SSB consumption was found, there was no association with fructose intake, suggesting that fructose is not the causal agent underlying the SSB-urate association. The abundant evidence supporting the inverse association between plasma urate concentration and dairy consumption should be reflected in dietary guidelines for hyperuricemic individuals and gout patients. Further research is needed to establish which nutrients and food products influence plasma urate

  18. 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

  19. [Acute renal failure in patients with tumour lysis sindrome].

    Science.gov (United States)

    Poskurica, Mileta; Petrović, Dejan; Poskurica, Mina

    2016-01-01

    `Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al.), as well as solid tumours (renal, liver, lung, ovarian, etc.), can lead to acute or chronic renal failure.The most common clinical manifestation is acute renal failure within the tumour lysis syndrome (TLS). It is characterized by specific laboratory and clinical criteria in order to prove that kidney disorders result from cytolysis of tumour cells after chemotherapy regimen given, although on significantly fewer occasions it is likely to occur spontaneously or after radiotherapy. Essentially, failure is the disorder of functionally conserved kidney or of kidney with varying degrees of renal insufficiency, which render the kidney impaired and unable to effectively eliminate the end products of massive cytolysis and to correct the resulting disorders: hyperuricemia, hyperkalemia, hypocalcaemia, hyperphosphatemia, and others. The risk of TLS depends on tumour size, proliferative potential of malignant cells, renal function and the presence of accompanying diseases and disorders. Hydration providing adequate diuresis and administration of urinary suppressants (allopurinol, febuxostat) significantly reduce the risk of developing TLS. If prevention of renal impairment isn't possible, the treatment should be supplemented with hemodynamic monitoring and pharmacological support, with the possible application of recombinant urate-oxidase enzyme (rasburicase). Depending on the severity of azotemia and hydroelectrolytic disorders, application of some of the methods of renal replacement therapy may be considered.

  20. Acute renal failure in patients with tumour lysis sindrome

    Directory of Open Access Journals (Sweden)

    Poskurica Mileta

    2016-01-01

    Full Text Available Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al., as well as solid tumours (renal, liver, lung, ovarian, etc., can lead to acute or chronic renal failure. The most common clinical manifestation is acute renal failure within the tumour lysis syndrome (TLS. It is characterized by specific laboratory and clinical criteria in order to prove that kidney disorders result from cytolysis of tumour cells after chemotherapy regimen given, although on significantly fewer occasions it is likely to occur spontaneously or after radiotherapy. Essentially, failure is the disorder of functionally conserved kidney or of kidney with varying degrees of renal insufficiency, which render the kidney impaired and unable to effectively eliminate the end products of massive cytolysis and to correct the resulting disorders: hyperuricemia, hyperkalemia, hypocalcaemia, hyperphosphatemia, and others. The risk of TLS depends on tumour size, proliferative potential of malignant cells, renal function and the presence of accompanying diseases and disorders. Hydration providing adequate diuresis and administration of urinary suppressants (allopurinol, febuxostat significantly reduce the risk of developing TLS. If prevention of renal impairment isn’t possible, the treatment should be supplemented with hemodynamic monitoring and pharmacological support, with the possible application of recombinant urate-oxidase enzyme (rasburicase. Depending on the severity of azotemia and hydroelectrolytic disorders, application of some of the methods of renal replacement therapy may be considered.

  1. The First U.S. Naval Observatory Robotic Astrometric Telescope Catalog (URAT1)

    CERN Document Server

    Zacharias, Norbert; Subasavage, John; Bredthauer, Greg; Crockett, Chris; DiVittorio, Mike; Ferguson, Erik; Harris, Fred; Harris, Hugh; Henden, Arne; Kilian, Chris; Munn, Jeff; Rafferty, Ted; Rhodes, Al; Schultheiss, Mike; Tilleman, Trudy; Wieder, Gary

    2015-01-01

    URAT1 is an observational, astrometric catalog covering most of the Dec >= -15 deg area and a magnitude range of about R = 3 to 18.5. Accurate positions (typically 10 to 30 mas standard error) are given for over 228 million objects at a mean epoch around 2013.5. For the over 188 million objects matched with the 2MASS point source catalog proper motions (typically 5 to 7 mas/yr std. errors) are provided. These data are supplemented by 2MASS and APASS photometry. Observations, reductions and catalog construction are described together with results from external data verifications. The catalog data are served by CDS, Starsbourg (I/329). There is no DVD release.

  2. Using serum urate as a validated surrogate end point for flares in patients with gout

    DEFF Research Database (Denmark)

    Birger Morillon, Melanie; Stamp, L.; Taylor, E W

    2016-01-01

    by applying the 'OMERACT Filter 2.0'. Methods and analysis: A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2...... independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate......, tophus size and number and pain at the final study visit (dependent variables). Ethics and dissemination: This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers...

  3. Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis.

    Science.gov (United States)

    Borghi, C; Perez-Ruiz, F

    2016-03-01

    In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently-used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout. The following efficacy outcomes were considered in the meta-analysis: (1) % of patients meeting the therapeutic target for sUA level (treatment of hyperuricaemia and gout. Febuxostat is a suitable pharmacological option for first line treatment of gout, given its established efficacy and safety, documented in a high number of clinical studies and in daily practice.

  4. [The combination of extracorporeal lithotripsy and percutaneous nephrostomy in the treatment of obstructive ureteral urate calculi].

    Science.gov (United States)

    Del Boca, C; Ferrari, C; Dotti, E; Corsi, G; Guardamagna, A; Giuberti, A C; Colloi, D

    1994-04-01

    The authors report their experience with combined percutaneous nephrostomy and extracorporeal shock-wave lithotripsy to treat obstructive uratic ureteral stones. The role of nephrostomy is stressed as a diagnosis and treatment method before, during and after lithotripsy. Thus, the method proved especially useful to drain obstructed kidneys and restore peristalsis, to evacuate septic urine, to facilitate the elimination of lithiasic fragments, to perform anterograde pyelography before, during and after lithotripsy and finally to allow pharmacological litholysis. Fourteen patients were successfully treated with combined extracorporeal lithotripsy and percutaneous nephrostomy and the results compared with those obtained with other techniques--e.g., ureteroscopy, whose value appears lower because the method requires general anesthesia and is more traumatic to the ureter. The authors conclude that combined extracorporeal lithotripsy and percutaneous nephrostomy make the best technique to treat obstructive uric acid stones thanks to their positive results, low invasiveness and to patients compliance.

  5. 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.

  6. Prophylaxis for acute gout flares after initiation of urate-lowering therapy.

    Science.gov (United States)

    Latourte, Augustin; Bardin, Thomas; Richette, Pascal

    2014-11-01

    This review summarizes evidence relating to prophylaxis for gout flares after the initiation of urate-lowering therapy (ULT). We searched MEDLINE via PubMed for articles published in English from 1963 to 2013 using MEsH terms covering all aspects of prophylaxis for flares. Dispersion of monosodium urate crystals during the initial phase of deposit dissolution with ULT exposes the patient to an increased rate of acute flares that could contribute to poor treatment adherence. Slow titration of ULT might decrease the risk of flares. According to the most recent international recommendation, the two first-line options for prophylaxis are low-dose colchicine (0.5 mg once or twice a day) or low-dose NSAIDs such as naproxen 250 mg orally twice a day. They can be given for up to 6 months. If these drugs are contraindicated, not tolerated or ineffective, low-dose corticosteroids (prednisone or prednisolone) might be used. Recently, reports for four trials described the efficacy of canakinumab and rilonacept, two IL-1 inhibitors, for preventing flares during the initiation of allopurinol therapy. Prophylaxis for flares induced by ULT is an important consideration in gout management. Low-dose colchicine and low-dose NSAIDs are the recommended first-line therapies. Although no IL-1 blockers are approved as prophylactic treatment, this class of drug could become an interesting option for patients with gout with intolerance or contraindication to colchicine, NSAIDs or corticosteroids. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Evaluation of renal donors and recipients using intravenous digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Deuk Lin; Kim, Ki Jeung [Soonchunhyang Medical College, Seoul (Korea, Republic of)

    1986-04-15

    Renal IV DSA was applied to evaluate 15 potential renal donors and 14 examinations of 12 renal allograft recipients. We evaluate the angiographic acute or chronic rejection, alteration of renal size after transplantation, excretion time of the contrast media and pre, post DSA serum creatinine level. DSA is a safe, easily performed, outpatient procedure and useful in evaluation and distinguishing status of surgical anastomosis, intrarenal vasculatures, arterial exception time and rejection phenomenon.

  8. Role of atrial receptors in the control of sodium excretion. [pressure breathing and antinatiuretic effects in dogs

    Science.gov (United States)

    Meehan, J. R.; Henry, J. P.

    1973-01-01

    Responses of an innervated and a contralateral chronically denervated kidney to mild positive pressure breathing are compared for saline volume expansions in chloralose anesthetized dogs. It is shown that mild pressure breathing significantly reduces sodium excretion, urine flow, free water clearance, and PAH clearance. After 20 minutes of positive pressure breathing, both kidney responses are identical suggesting the release of natriuretic hormone which reduces renal function in addition to the demonstrated change in renal nerve activity. Increase of the left atrial pressure through balloon obstruction of the mitral orifice increases urine flow, sodium excretion and PAH clearance; inflation of the balloon and positive pressure breathing again depresses renal function. Preliminary evidence indicates that receptors in the right atrium are more severely affected by pressure breathing than those in the left atrium.

  9. 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.

  10. Renal effects of acute exposure to toluene. A controlled clinical trial

    DEFF Research Database (Denmark)

    Nielsen, H K; Krusell, Lars Romer; Bælum, Jesper

    1985-01-01

    Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin...... and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury....

  11. Ammonia distribution and excretion in fish.

    Science.gov (United States)

    Randall, D J; Wright, P A

    1987-05-01

    This paper reviews the literature concerning ammonia production, storage and excretion in fish. Ammonia is the end product of protein catabolism and is stored in the body of fish in high concentrations relative to basal excretion rates. Ammonia, if allowed to accumulate, is toxic and is converted to less toxic compounds or excreted. Like other weak acids and bases, ammonia is distributed between tissue compartments in relation to transmembrane pH gradients. NH3 is generally equilibrated between compartments but NH4 (+) is distributed according to pH. Ammonia is eliminated from the blood upon passage through the gills. The mechanisms of branchial ammonia excretion vary between different species of fish and different environments, and primarily involves NH3 passive diffusion and NH4 (+)/Na(+) exchange. Water chemistry near the gill surface may also be important to ammonia excretion, but a more accurate measurement of the NH3 gradient across the gill epithelium is required before a more detailed analysis of NH3 and NH4 (+) excretion can be made.

  12. Urinary excretion of arginine-vasopressin and prostaglandin E in essential fatty acid-deficient rats after oral supplementation with unsaturated fatty acid esters

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1986-01-01

    supplementation period, were analyzed for volume, and by radioimmunoassay for arginine-vasopressin (AVP) and prostaglandin E (PGE). Linoleate and arachidonate supplements both decreased the initial high urinary AVP excretion, whereas it was further increased by the oleate supplement. There was no effect...... excretion and the percentage of arachidonate or the ratio of 20:3 (n=9)/20:4(n-6) in total kidney lipids. It is suggested that increased urinary AVP excretion in EFA-deficient rats is mainly caused by a change in the renal excretatory mechanism of AVP rather than reflecting an increased plasma AVP...

  13. A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria.

    Science.gov (United States)

    Tamma, Grazia; Di Mise, Annarita; Ranieri, Marianna; Svelto, Maria; Pisot, Rado; Bilancio, Giancarlo; Cavallo, Pierpaolo; De Santo, Natale G; Cirillo, Massimo; Valenti, Giovanna

    2014-05-19

    Exposure to microgravity or immobilization results in alterations of renal function, fluid redistribution and bone loss, which couples to a rise of urinary calcium excretion. We recently demonstrated that high calcium delivery to the collecting duct reduces local Aquaporin-2 (AQP2) mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration and reducing calcium saturation. To investigate renal water balance adaptation during bed rest, a model to mimic the effects of microgravity on earth, the effect of changes in urinary calcium on urinary AQP2 excretion were assessed. Ten healthy men (aged 21-28 years) participated in the experiment. Study design included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0 and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine samples were collected daily from day -3 to 35. Changes in blood hematocrit were used as an indirect index of plasma volume changes. AQP2 excretion was measured by ELISA. Bed rest induced bone demineralization and a transient increase in urinary calcium followed by transient decrease in AQP2 excretion, which can reduce the urine concentrating ability causing plasma volume reduction. The return of calciuria to baseline was followed by a recovery of AQP2 excretion, which allows for a partial restoration of plasma volume. These results further support the view that urinary calcium can modulate the vasopressin-dependent urine concentration through a down-regulation of AQP2 expression/trafficking. This mechanism could have a key role in the prevention of urine super-saturation due to hypercalciuria.

  14. Discovery of Flexible Naphthyltriazolylmethane-based Thioacetic Acids as Highly Active Uric Acid Transporter 1 (URAT1) Inhibitors for the Treatment of Hyperuricemia of Gout.

    Science.gov (United States)

    Zhang, Xiansheng; Wu, Jingwei; Liu, Wei; Liu, Yuqiang; Xie, Yafei; Shang, Qian; Zhou, Zhixing; Xu, Weiren; Tang, Lida; Wang, Jianwu; Zhao, Guilong

    2017-01-01

    Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT1) was the promising therapeutic target for urate-lowering therapy. The goal of this work is to understand the structure-activity relationship (SAR) of a potent lesinurad-based hit, sodium 2-((5-bromo-4-((4-cyclopropyl-naphth-1-yl)methyl)-4H-1,2,4-triazol-3- yl)thio)acetate (1c), and based on that discover a more potent URAT1 inhibitor. The SAR of 1c was systematically explored and the in vitro URAT1 inhibitory activity of synthesized compounds 1a-1t was determined by the inhibition of URAT1-mediated [8-14C]uric acid uptake by human embryonic kidney 293 (HEK293) cells stably expressing human URAT1. Twenty compounds 1a-1t were synthesized. SAR analysis was performed. Two highly active URAT1 inhibitors, sodium 2-((5-bromo-4-((4-n-propylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3- yl)thio)acetate (1j) and sodium 2-((5-bromo-4-((4-bromonaphth-1-yl)methyl)-4H-1,2,4-triazol-3- yl)thio)acetate (1m), were identified, which were 78- and 76-fold more active than parent lesinurad in in vitro URAT1 inhibitory assay, respectively (IC50 values for 1j and 1m were 0.092 μM and 0.094 μM, respectively, against human URAT1 vs 7.18 μM for lesinurad). Two highly active URAT1 inhibitors were discovered. The SAR exploration also identified more flexible naphthyltriazolylmethane as a novel molecular skeleton that will be valuable for the design of URAT1 inhibitors, as indicated by the observation that many of the synthesized naphthyltriazolylmethane- bearing derivatives (1b-1d, 1g, 1j and 1m) showed significantly improved UART1 inhibitory activity (sub-micromolar IC50 values) as compared with lesinurad which has the rigid naphthyltriazole skeleton. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Chronic effects of methylmercury on the urinary excretion of catecholamines and their responses to hypoglycemic stress

    Energy Technology Data Exchange (ETDEWEB)

    Kabuto, M. (Japan National Inst. of Environmental Studies (NIES), Tsukuba, Ibaraki (Japan). Dept. of Environmental Health)

    1991-02-01

    Five male Wistar rats were treated with methylmecury chloride (MMC) and compared with five agematched control rats. A dose of 10 mg/kg was given three times. The chronic effects of the MMC administration on the urinary output of catecholamines (norepinephrine (NE), epinephrine (E) and dopamine (DA)) were measured for 50 days. On the 69th day after MMC administration, the rats were examined for insulin-induced hypoglycemic stress. On the 90th day, the animals were decapitated and various organs were weighted and serum thyroid hormones (thyroid stimulating hormone (TSH) and total and free thyroxine (T4)) were measured. Decreases in DA excretion and DA response to stress were observed in the MMC-treated group. Inflammation of the kidney was also found, suggesting MMC-induced damage to the renal tubular region, the apparent site of renal DA synthesis. The MMC group and the control group showed differential NE and E response patterns. The lowered baseline excretion of NE appeared to continue even 70 days after MMC administration, while the difference in E excretion between the two groups disappeared 1 month after MMC administration. Both NE and E showed normal responsiveness to hypoglycemic stress induced by insulin. All serum TSH and total and free T4 baseline levels showed slight increases, and the thyroid gland weights in the MMC group were slightly heavier. These findings suggest a rather hyperthyroid state after the initial acute phase suppression, as suggested by the previous examinations. Thus, these findings suggest long-lasting effects of methylmercury administration, especially on renal DA synthesis. Baseline urinary excretion of NE and thyroid function could also be affected for a long time. (orig.).

  16. Urate crystal deposition and bone erosion in gout: 'inside-out' or 'outside-in'? A dual-energy computed tomography study.

    Science.gov (United States)

    Towiwat, Patapong; Doyle, Anthony J; Gamble, Gregory D; Tan, Paul; Aati, Opetaia; Horne, Anne; Stamp, Lisa K; Dalbeth, Nicola

    2016-09-15

    It is currently unknown whether bone erosion in gout occurs through an 'inside-out' mechanism due to direct intra-osseous crystal deposition or through an 'outside-in' mechanism from the surface of bone. The aim of this study was to examine the mechanism ('outside-in' vs. 'inside-out') of monosodium urate (MSU) crystal deposition in bone erosion in gout. Specifically, we used three-dimensional dual-energy computed tomography (DECT) to analyse the positional relationship between bone and MSU crystal deposition in tophaceous gout, and to determine whether intra-osseous crystal deposition occurs in the absence of erosion. One hundred forty-four participants with gout and at least one palpable tophus had a DECT scan of both feet. Two readers independently scored all metatarsal heads (1433 bones available for scoring). For bones in contact with urate, the bone was scored for whether urate was present within an erosion, on the surface of bone or within bone only (true intra-osseous deposit). Data were analysed using generalised estimating equations. Urate in contact with bone was present in 370 (54.3 %) of 681 joints with urate deposition. For those bones in contact with urate, deposition was present on the surface of bone in 143 (38.6 %) of 370 joints and within erosion in 227 (61.4 %) of 370. True intra-osseous urate deposition was not observed at any site (p in one plane, examination in other planes revealed urate deposition within an en face erosion. In tophaceous gout, MSU crystal deposition is present within the joint, on the bone surface and within bone erosion, but it is not observed within bone in the absence of a cortical break. These data support the concept that MSU crystals deposit outside bone and contribute to bone erosion through an 'outside-in' mechanism.

  17. 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 ...

  18. MR to assess renal function in children

    Energy Technology Data Exchange (ETDEWEB)

    Rohrschneider, Wiltrud K.; Troeger, Jochen [Department of Pediatric Radiology, Radiological Clinic, University of Heidelberg, Im Neuenheimer Feld 153, 69120, Heidelberg (Germany); Haufe, Sabine [Department of Nuclear Medicine, Radiological University Clinic Heidelberg, Im Neuenheimer Feld 153, 69120, Heidelberg (Germany); Clorius, John H. [Department of Nuclear Medicine, German Cancer Research Institute, 69120, Heidelberg (Germany)

    2003-05-01

    Renal function evaluation in the pediatric patient is generally based on scintigraphic examinations where a baseline gamma-camera renography is used to determine single kidney function, and diuresis renography is obtained to assess urinary drainage from the pelvicalyceal system. Magnetic resonance imaging also permits the evaluation of renal functional processes using fast dynamic sequences. Principally, an agent cleared by renal excretion is intravenously injected and its cortical uptake, parenchymal transport, and eventually its urinary excretion are followed with serial images. Different approaches have been presented most of which are based on T1-weighted gradient-recalled echo sequences with short TR and TE and a low flip angle obtained after intravenous injection of Gd-DTPA or Gd-DOTA. These techniques permit renal functional assessment using different qualitative and quantitative parameters; however, most of these methods are not suitable for the evaluation of urinary tract dilatation in infants and children. For the diagnostic work-up of children with congenital urinary tract obstruction and malformation a technique was developed which permits quantitative determination of single kidney function, in addition to evaluating urinary excretion disturbances analogous to that possible with scintigraphy. (orig.)

  19. The Reduction in Urinary Glutamate Excretion Is Responsible for Lowering Urinary pH in Pink Urine Syndrome.

    Science.gov (United States)

    Ogawa, Susumu; Takiguchi, Junko; Shimizu, Manami; Nako, Kazuhiro; Okamura, Masashi; Kinouchi, Yoshitaka; Ito, Sadayoshi

    2016-06-01

    We frequently encounter brownish-red, cloudy urine in some obese subjects, which occurs due to pink urine syndrome (PUS). PUS is a phenomenon in which uric acid precipitates into the urine due to reduced urinary pH (UpH). The mechanism underlying urinary acidification has not been elucidated so far. UpH level is adjusted by urinary excretion of ammonia synthesized from glutamate or glutamine, suggesting that renal synthesis of ammonia from glutamate or glutamine is decreased in PUS. However, this hypothesis has not been examined yet. We therefore examined the changes in the urinary excretion of these amino acids in PUS. One-hundred-fifty male students who had undergone a physical examination were enrolled. To determine the presence [PUS (+), n = 72] or absence [PUS (-), n = 78] of PUS, urinary amino acid excretion and UpH were evaluated. Independent risk factors of lower UpH were determined using multiple regression analyses. The PUS (+) subjects, who had lower UpH values than PUS (-) subjects, showed lower urinary excretion of glutamate and some other glucogenic amino acids. Thus, UpH correlated positively with the urinary excretion of glutamate in the PUS (+) subjects. A reduction in urinary glutamate but not in glutamine excretion proved to be an independent risk factor for reduced UpH. In conclusion, PUS appears to occur when a reduction in the synthesis of ammonia from glutamate causes a decrease in UpH. Our results showed that urinary glutamate excretion was reduced in PUS because renal glutamate was consumed by a reaction different from ammonia production.

  20. Renal dopamine receptors and hypertension.

    Science.gov (United States)

    Hussain, Tahir; Lokhandwala, Mustafa F

    2003-02-01

    Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

  1. General base catalysis in the urate oxidase reaction: evidence for a novel Thr-Lys catalytic diad.

    Science.gov (United States)

    Imhoff, Rebecca D; Power, Nicholas P; Borrok, M Jack; Tipton, Peter A

    2003-04-15

    Urate oxidase catalyzes the oxidation of urate without the involvement of any cofactors. The gene encoding urate oxidase from Bacillus subtilis has been cloned and expressed, and the enzyme was purified and characterized. Formation of the urate dianion is believed to be a key step in the oxidative reaction. Rapid-mixing chemical quench studies provide evidence that the dianion is indeed an intermediate; at 15 degrees C the dianion forms within the mixing time of the rapid-quench instrument, and it disappears with a rate constant of 8 s(-)(1). Steady-state kinetic studies indicate that an ionizable group on the enzyme with a pK of 6.4 must be unprotonated for catalysis, and it is presumed that the role of this group is to abstract a proton from the substrate. Surprisingly, examination of the active site provided by the previously reported crystal structure does not reveal any obvious candidates to act as the general base. However, Thr 69 is hydrogen-bonded to the ligand at the active site, and Lys 9, which does not contact the ligand, is hydrogen-bonded to Thr 69. The T69A mutant enzyme has a V(max) that is 3% of wild type, and the K9M mutant enzyme has a V(max) that is 0.4% of wild type. The ionization at pH 6.4 that is observed with wild-type enzyme is absent in both of these mutants. It is proposed that these residues form a catalytic diad in which K9 deprotonates T69 to allow it to abstract the proton from the N9 position of the substrate to generate the dianion.

  2. Systemic staging for urate crystal deposits with dual-energy CT and ultrasound in patients with suspected gout.

    Science.gov (United States)

    Huppertz, Alexander; Hermann, Kay-Geert A; Diekhoff, Torsten; Wagner, Moritz; Hamm, Bernd; Schmidt, Wolfgang A

    2014-06-01

    Objective of the study is to compare the diagnostic accuracy for detecting monosodium urate crystal deposits between dual-energy CT (DECT) and ultrasound (US). Sixty consecutive patients (49 men, mean age 62 years) with clinically suspected gout were included in this case-control study. DECT and US of feet, knees, hands and elbows were performed in all patients. Polarisation microscopy of synovial fluid or a score incorporating serum uric acid level, first MTP joint involvement, gender, previous patient-reported arthritis attack, cardiovascular diseases, joint redness and onset within 1 day was used as standard of reference. Standard of reference classified 39 patients as gout positive. Sixteen patients had gout and a concomitant rheumatic disease. Sensitivities for diagnosis of gout disease were 84.6 % (33/39) for DECT and 100 % (39/39) for US. Specificities were 85.7 % (18/21) for DECT and 76.2 % (16/21) for US. Positive and negative predictive values were 91.7 % (33/36) and 75.0 % (18/24) for DECT, 88.6 % (39/44) and 100 % (16/16) for US, respectively. Urate crystals were detected most frequently in MTP1 joints (DECT 20/78, US 58/78), any other toe joints (DECT 25/78, US 62/78) and knees (DECT 41/78, US 31/78). The volumetry of DECT computed a mean urate crystal deposit load of 2.1 cm(3) (SD 9.6 cm(3)). A mean effective dose of ≤0.5 mSv was estimated. DECT is more specific for the diagnosis of gout than US. However, it fails to detect small urate crystal deposits. It might be particularly useful for patients with ambivalent findings, concomitant rheumatic diseases and with non-conclusive joint aspiration.

  3. Protein adsorption to monosodium urate crystals: differential responses of human peripheral blood neutrophils. [Etiology of acute gouty arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Skosey, J.L.; Kozin, F.; Ginsberg, M.

    1976-01-01

    In order for acute gouty arthritis to occur, neutrophils must interact with monosodium urate (MSU) crystals. As a result of this interaction, enzymes, chemotactic factors, and other mediators of the inflammatory response are released from neutrophil lysosomes. It was observed that MSU crystals adsorb gamma globulin, albumin, and other proteins found in serum and joint fluid. Results are reported from a study designed to demonstrate the effects of coating of MSU crystals with proteins on the phlogistic responses of neutrophils to crystals.

  4. Excreting and non-excreting grasses exhibit different salt resistance strategies

    Science.gov (United States)

    Moinuddin, Muhammad; Gulzar, Salman; Ahmed, Muhammad Zaheer; Gul, Bilquees; Koyro, Hans-Werner; Khan, Muhammad Ajmal

    2014-01-01

    The combination of traits that makes a plant successful under saline conditions varies with the type of plant and its interaction with the environmental conditions. Knowledge about the contribution of these traits towards salt resistance in grasses has great potential for improving the salt resistance of conventional crops. We attempted to identify differential adaptive response patterns of salt-excreting versus non-excreting grasses. More specifically, we studied the growth, osmotic, ionic and nutrient (carbon/nitrogen) relations of two salt-excreting (Aeluropus lagopoides and Sporobolus tremulus) and two non-excreting (Paspalum paspalodes and Paspalidium geminatum) perennial C4 grasses under non-saline and saline (0, 200 and 400 mM NaCl) conditions. Growth and relative growth rate decreased under saline conditions in the order P. geminatum > S. tremulus = A. lagopoides > P. paspalodes. The root-to-shoot biomass allocation was unaffected in salt-excreting grasses, increased in P. paspalodes but decreased in P. geminatum. Salt-excreting grasses had a higher shoot/root Na+ ratio than non-excreting grasses. K+, Ca2+ and Mg2+ homoeostasis remained undisturbed among test grasses possibly through improved ion selectivity with rising substrate salinity. Salt-excreting grasses increased leaf succulence, decreased ψs and xylem pressure potential, and accumulated proline and glycinebetaine with increasing salinity. Higher salt resistance of P. paspalodes could be attributed to lower Na+ uptake, higher nitrogen-use efficiency and higher water-use efficiency among the test species. However, P. geminatum was unable to cope with salt-induced physiological drought. More information is required to adequately document the differential strategies of salt resistance in salt-excreting and non-excreting grasses. PMID:24996428

  5. Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle

    Directory of Open Access Journals (Sweden)

    Tyagi Suresh

    2004-01-01

    Full Text Available Abstract Background The topical role of uric acid and its relation to cardiovascular disease, renal disease, and hypertension is rapidly evolving. Its important role both historically and currently in the clinical clustering phenomenon of the metabolic syndrome (MS, type 2 diabetes mellitus (T2DM, atheroscleropathy, and non-diabetic atherosclerosis is of great importance. Results Uric acid is a marker of risk and it remains controversial as to its importance as a risk factor (causative role. In this review we will attempt to justify its important role as one of the many risk factors in the development of accelerated atherosclerosis and discuss its importance of being one of the multiple injurious stimuli to the endothelium, the arterial vessel wall, and capillaries. The role of uric acid, oxidative – redox stress, reactive oxygen species, and decreased endothelial nitric oxide and endothelial dysfunction cannot be over emphasized. In the atherosclerotic prooxidative environmental milieu the original antioxidant properties of uric acid paradoxically becomes prooxidant, thus contributing to the oxidation of lipoproteins within atherosclerotic plaques, regardless of their origins in the MS, T2DM, accelerated atherosclerosis (atheroscleropathy, or non-diabetic vulnerable atherosclerotic plaques. In this milieu there exists an antioxidant – prooxidant urate redox shuttle. Conclusion Elevations of uric acid > 4 mg/dl should be considered a "red flag" in those patients at risk for cardiovascular disease and should alert the clinician to strive to utilize a global risk reduction program in a team effort to reduce the complications of the atherogenic process resulting in the morbid – mortal outcomes of cardiovascular disease.

  6. Iodine excretion in school children in Copenhagen

    DEFF Research Database (Denmark)

    Rasmussen, Lone B; Kirkegaard-Klitbo, Ditte Marie; Laurberg, Peter

    2016-01-01

    according to grade. The UIC was higher in children than in adults from the same area. CONCLUSIONS: The iodine excretion among schoolchildren in Copenhagen, an area with a relatively high iodine content in tap water, was within the recommended range as assessed by the UIC. An increased iodine fortification......INTRODUCTION: Studies of dietary habits show a high iodine intake in children in Denmark. Iodine excretion in children has not previously been assessed. Iodine excretion in adults is below the recommended threshold, and it is therefore being discussed to increase the fortification level. The main...... will not have negative consequences for this group. FUNDING: The Ministry of Food, Agriculture and Fisheries. TRIAL REGISTRATION: not relevant....

  7. Preventing attacks of acute gout when introducing urate-lowering therapy: a systematic literature review.

    Science.gov (United States)

    Seth, Rakhi; Kydd, Alison S R; Falzon, Louise; Bombardier, Claire; van der Heijde, Désirée M; Edwards, Christopher J

    2014-09-01

    To systematically review the evidence on treatment available to prevent an acute attack of gout when initiating a urate-lowering therapy (ULT) and for how long this treatment should be continued. To also evaluate the evidence on the optimal time to start a ULT after an acute attack of gout. A systematic review as part of the 3e (Evidence, Expertise, Exchange) Initiative on Diagnosis and Management of Gout was performed using Medline, Embase, Cochrane Central Register of Controlled Trials (from 1950 to October 2011), and the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) 2010/2011 meeting abstracts. Two reviewers independently screened titles and abstracts for selection criteria. Included articles were reviewed in detail, and a risk of bias assessment (using the Cochrane tool) was performed. The search identified 8168 articles and 197 abstracts, from which 4 randomized controlled trials were included in the review. Two of these studies compared placebo with colchicine, 1 compared differing durations of colchicine, and 1 compared colchicine with canakinumab. Two randomized controlled trials have shown that colchicine prophylaxis for at least 6 months, when starting a ULT, reduces the risk of acute attacks. Canakinumab, although not currently licensed for gout, has been shown to provide prophylaxis superior to colchicine, when starting a ULT. There is no evidence on the optimum time to start a ULT after an acute gout attack.

  8. Adequacy of Online Patient Information Resources on Gout and Potentially Curative Urate-Lowering Treatment.

    Science.gov (United States)

    Jimenez-Liñan, L M; Edwards, L; Abhishek, A; Doherty, Michael

    2017-05-01

    To assess the content and readability of online patient information resources against the current understanding of gout. An online survey was undertaken using Google UK, USA, Australia, and Canada. Information was assessed for content and accuracy on 19 key points regarding core content for gout patient information resources. Readability was assessed using the Flesch-Kincaid Reading Ease score. Fifteen randomly selected websites were reviewed by a blinded second observer. A total of 85 websites were selected. More than 50% of the websites provided no information or had inaccuracies regarding the pathogenesis of gout. Most websites contained information on dietary and lifestyle modifications for treating gout and did not emphasize urate-lowering therapy (ULT) and its potential for cure. Over 75% of the websites had no/inaccurate information on the role of ULT or prophylaxis for preventing gout attacks on starting ULT. The majority of websites were difficult to read, with information in 68% of the websites rated at least fairly difficult. Only a few web-based patient information resources provide accurate and easy-to-read information on gout. This study will help physicians direct patients to currently reliable resources, but there is a need to improve many web-based patient information resources, which at present act as barriers to care. © 2016, American College of Rheumatology.

  9. Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension

    NARCIS (Netherlands)

    van Paassen, P; Navis, GJ; de Jong, PE; de Zeeuw, D

    1999-01-01

    Background In essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin-angiotensin-aldosterone system-mediated impairment of renal sodium excretion. This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic respon

  10. Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis

    Science.gov (United States)

    Morillon, Melanie B; Stamp, Lisa; Taylor, William; Fransen, Jaap; Dalbeth, Nicola; Singh, Jasvinder A; Lassere, Marissa

    2016-01-01

    Introduction Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the ‘Biomarker-Surrogacy Evaluation Schema version 3’ (BSES3), documenting the validity of selected instruments by applying the ‘OMERACT Filter 2.0’. Methods and analysis A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables). Ethics and dissemination This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications. Trial registration number CRD42016026991. PMID:27650765

  11. 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.

  12. 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...

  13. Zhang Qi's Experience in Treating Chronic Renal Failure

    Institute of Scientific and Technical Information of China (English)

    LIN Qi-zhan; XU Da-ji; MA Yu-peng

    2008-01-01

    @@ Chronic renal failure is a result of the parenchymatous injury of kidney and progressive exacerbation due to many reasons.It is a svstematic clinical syndrome caused by the disturbance in excreting metabolites,adjusting water-electrolyte and acid-base balance as well as production and inactivation of active substances of endocrine.Prof Zhang Qi has rich clinical experience in treating renal failure.A report follows.

  14. Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion

    Science.gov (United States)

    Aswania, O A; Corlett, S A; Chrystyn, H

    1999-01-01

    Aims To determine if a urinary excretion method, previously described for salbutamol, could also indicate the relative bioavailability of sodium cromoglycate to the lung following inhalation from a metered dose inhaler. Method Inhaled (INH), inhaled+oral charcoal (INHC), oral (ORAL) and oral+oral charcoal (ORALC) 20 mg doses of sodium cromoglycate were given via a randomised cross-over design to 11 healthy volunteers trained on how to use a metered dose inhaler. Urine samples were collected at 0.0, 0.5, 1.0 and up to 24 h post dosing and the sodium cromoglycate urinary concentration was measured using a high performance liquid chromatographic method. Results No sodium cromoglycate was detected in the urine up to 24 h following ORALC dosing. A mean (s.d.) of 3.6 (4.3) μg, 10.4 (10.9) μg and 83.7 (71.1) μg of the ORAL dose was excreted, in the urine, during the 0.5, 1.0 and 24 h post dose collection periods, respectively. Following INH dosing, the renal excretion was significantly higher (P < 0.01) with 32.9 (14.5) μg, 61.2 (28.3) μg and 305.6 (82.3) μg excreted, respectively. The SCG excreted at 0.5, 1.0 and 24 h collection periods following INHC dosing were 26.3 (8.4) μg, 49.3 (18.1) μg and 184.9 (98.4) μg, respectively. There was no significant difference between the excretion rate of sodium cromoglycate following INHC when compared with INH dosing in the first 0.5 and 1.0 h. Conclusions The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body

  15. Control of potassium excretion: a Paleolithic perspective.

    Science.gov (United States)

    Halperin, Mitchell L; Cheema-Dhadli, Surinder; Lin, Shih-Hua; Kamel, Kamel S

    2006-07-01

    Regulation of potassium (K) excretion was examined in an experimental setting that reflects the dietary conditions for humans in Paleolithic times (high, episodic intake of K with organic anions; low intake of NaCl), because this is when major control mechanisms were likely to have developed. The major control of K secretion in this setting is to regulate the number of luminal K channels in the cortical collecting duct. Following a KCl load, the K concentration in the medullary interstitial compartment rose; the likely source of this medullary K was its absorption by the H/K-ATPase in the inner medullary collecting duct. As a result of the higher medullary K concentration, the absorption of Na and Cl was inhibited in the loop of Henle, and this led to an increased distal delivery of a sufficient quantity of Na to raise K excretion markedly, while avoiding a large natriuresis. In addition, because K in the diet was accompanied by 'future' bicarbonate, a role for bicarbonate in the control of K secretion via 'selecting' whether aldosterone would be a NaCl-conserving or a kaliuretic hormone is discussed. This way of examining the control of K excretion provides new insights into clinical disorders with an abnormal plasma K concentration secondary to altered K excretion, and also into the pathophysiology of calcium-containing kidney stones.

  16. Power Functions Relating Excretion to Body Burden

    CERN Document Server

    Sanders, S M J

    2003-01-01

    Formulae necessary to relate the quantity of radionuclides excreted to that assimilated in exposures that are acute and those that are multiple or continuous are derived from power function relationships. Particular attention is given to providing equations having variables for which the bioassayer can easily derive numerical values. This paper presents this data.

  17. Urinary excretion of Iopamidol following intrathecal administration.

    Science.gov (United States)

    Pitrè, D; Zingales, M F; Trevisan, C

    1983-01-01

    No iodinated compound other than Iopamidol was found in the urine of subjects who received intrathecal injection of 10 ml of Iopamiro "300". The compound was neither metabolized nor altered in its optical configuration and urinary iodide content was always in the normal range. Between 72 and 85% of injected Iopamidol was excreted within 72 h of injection.

  18. Urinary growth hormone excretion in acromegaly

    DEFF Research Database (Denmark)

    Main, K M; Lindholm, J; Vandeweghe, M

    1993-01-01

    The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly...

  19. Renal injury due to hepatic hydatid disease.

    Science.gov (United States)

    Altay, Mustafa; Unverdi, Selman; Altay, Fatma Aybala; Ceri, Mevlüt; Akay, Hatice; Ozer, Hüseyin; Kiraç, Halil; Denizli, Nazim; Yilmaz, Bilal; Güvence, Necmettin; Duranay, Murat

    2010-08-01

    Many studies on renal hydatid disease have been reported in the literature, and the disease process appears to be well defined. However, renal injury without direct renal invasion remains poorly understood. The present study aims to define the frequency and the property of the renal involvement in hydatid disease. Eighty patients older than 18 years and diagnosed with liver echinococcosis were included in the study. The echinococcosis was diagnosed by the haemagglutination test and abdominal ultrasonography. Twenty-four-hour protein excretion was measured for patients who had elevated serum creatinine levels or whose urinalyses were positive for haematuria or proteinuria. Subsequently, renal biopsy was performed, and the specimens were examined by light microscopy and immunofluorescence staining. Haematuria was detected in 11 patients (13.75%), and proteinuria was detected in nine patients (11.25%). Percutaneous renal biopsy was applied to nine patients who gave signed consents to undergo the test. We detected four immunoglobulin A nephritis (together with tubulointerstitial nephritis in one patient), one membranoproliferative glomerulonephritis, one immunoglobulin M nephritis together with mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one amyloidosis and one tubulointerstitial nephritis. Renal hydatid cyst was detected only in four patients (5%). Hydatid disease, which affects the kidney, is not rare, and we suggest that urinalysis and, if indicated, renal biopsy should be performed for hepatic hydatid disease diagnosis.

  20. 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...

  1. Renal sodium handling and sodium sensitivity

    Directory of Open Access Journals (Sweden)

    Alissa A. Frame

    2017-06-01

    Full Text Available The pathophysiology of hypertension, which affects over 1 billion individuals worldwide, involves the integration of the actions of multiple organ systems, including the kidney. The kidney, which governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters, is central to long term blood pressure regulation and the salt sensitivity of blood pressure. The impact of renal sodium handling and the salt sensitivity of blood pressure in health and hypertension is a critical public health issue owing to the excess of dietary salt consumed globally and the significant percentage of the global population exhibiting salt sensitivity. This review highlights recent advances that have provided new insight into the renal handling of sodium and the salt sensitivity of blood pressure, with a focus on genetic, inflammatory, dietary, sympathetic nervous system and oxidative stress mechanisms that influence renal sodium excretion. Increased understanding of the multiple integrated mechanisms that regulate the renal handling of sodium and the salt sensitivity of blood pressure has the potential to identify novel therapeutic targets and refine dietary guidelines designed to treat and prevent hypertension.

  2. Control of sodium excretion by angiotensin II: intrarenal mechanisms and blood pressure regulation.

    Science.gov (United States)

    Hall, J E

    1986-06-01

    Angiotensin II (ANG II) is one of the body's most powerful regulators of Na excretion, operating through extrarenal mechanisms, such as stimulation of aldosterone secretion, as well as intrarenal mechanisms. Considerable evidence suggests that the intrarenal actions of ANG II are quantitatively more important than changes in aldosterone secretion in the normal day-to-day regulation of Na balance and arterial pressure. ANG II at physiological concentrations increases proximal tubular reabsorption, but further studies are needed to determine whether ANG II also has an important effect on more distal tubular segments. ANG II also markedly constricts efferent arterioles, tending to increase Na reabsorption by altering peritubular capillary physical forces and also helping to prevent excessive decreases in glomerular filtration rate. ANG II may also decrease Na excretion and increase urine concentrating ability by reducing renal medullary blood flow. Regulation of Na excretion by ANG II is closely linked with arterial pressure control and volume homeostasis through the renal pressure natriuresis mechanism. Under many physiological conditions, such as changes in Na intake, ANG II greatly multiplies the effectiveness of the pressure natriuresis mechanism to prevent fluctuations in body fluid volume and arterial pressure. In circumstances associated with circulatory depression, such as decreased cardiac function, reductions in blood pressure and increased ANG II formation cause Na retention until arterial pressure is restored to normal. However, in pathophysiological conditions in which ANG II is inappropriately elevated, increased arterial pressure (hypertension) is required for the kidney to "escape" the potent antinatriuretic actions of ANG II and to return Na excretion to normal via the pressure natriuresis mechanism.

  3. Sodium excretion following central administration of an I1 imidazoline receptor agonist, moxonidine.

    Science.gov (United States)

    Penner, S. B.; Smyth, D. D.

    1994-01-01

    1. Previously we have shown that an intrarenal infusion of moxonidine, an I1-imidazoline receptor agonist, resulted in a natriuresis which was inhibited by intravenous idazoxan, a selective imidazoline receptor antagonist. Therefore we examined the effects of renal function of intracerebroventricular (i.c.v.) administration of moxonidine with or without i.c.v. idazoxan. 2. Seven days after unilateral nephrectomy, Sprague-Dawley rats had i.c.v. cannulae implanted. Three days later the rats were anaesthetized (pentobarbitone), followed by cannulation of the jugular vein (fluid and drug administration), carotid artery (blood pressure) and the ureter (urine collection). 3. After a 45 min stabilization period, the effect of moxonidine was investigated by the i.c.v. administration of either isotonic saline or moxonidine (0.1, 0.3 or 1 nmol in isotonic saline) administered in 5 microliters over 1 min. All doses of moxonidine resulted in an increase in urine flow with a concomitant increase in sodium excretion without affecting blood pressure. The highest dose of moxonidine (1 nmol) also increased free water clearance. 4. In a second series of experiments, the effects of idazoxan on the natriuretic response to i.c.v. moxonidine were determined. Moxonidine (0.3 nmol) again increased sodium and water excretion as compared to the i.c.v. saline control animals. Pretreatment with i.c.v. idazoxan (0.3 nmol), at a dose which alone failed to alter sodium and water excretion, completely attenuated the renal response to moxonidine. These results are consistent with central I1-imidazoline receptors mediating a moxonidine-induced increase in sodium and water excretion at doses that do not alter blood pressure. PMID:7952868

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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....

  10. Renal adaptation to metabolic acidosis in senescent rats

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, R.; Kinsella, J.L.; Sacktor, B. (National Institutes of Health, Baltimore, MD (USA))

    1988-12-01

    In this study, the authors compared results obtained in senescent rats with young rats given an equivalent acid load. They examined the renal changes by giving equivalent acid loads for 48 h to both 6- and 24-mo-old rats. The basal excretion of ammonium was the same in both groups, whereas titratable acids, phosphate, and Ca{sup 2+} excretions were increased in the senescent animal. After administration of the acid load, ammonium, phosphate, Ca{sup 2+}, and titratable acid excretions increased in both age groups, but there were greater absolute increases in ammonium and titratable acid excretions in the young rats. The total acid excreted by the 24-mo rats was reduced 50 (day 1) and 25% (day 2) compared with the young rats, which was reflected by the more severe acidosis in those animals. The portion of total acid excreted as titratable acids in senescent animals was also increased during acidosis when compared with the young animals. In isolated proximal tubule brush-border membrane vesicles, acidosis increased Na{sup +}-H{sup +} exchange and decreased Na{sup +}-dependent phosphate transport in both age groups. They also found that the basal activity of the Na{sup +}-H{sup +} exchanger was not changed with age but the Na{sup +} dependent phosphate transporter was less in the 24-mo rat. The results suggest that physiological regulation of these renal processes remains intact in the aged rat but the responses may be reduced or delayed in the senescent animal.

  11. Phenolsulfonphthalein test in healthy sheep and in sheep with reductions in functional renal mass.

    Science.gov (United States)

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

    1985-03-01

    The phenolsulfonphthalein (PSP) plasma clearance and urinary excretion tests were applied to sheep before and after 50% and 75% reductions in functional renal mass. The PSP determinants found most useful as indicators of renal mass reduction were the 15-minute urinary excretion percentage and the 60-minute (PSP60) plasma concentration. Although both of these determinants could be used to detect renal mass reduction, the 15-minute PSP excretion percentage was the more sensitive. The PSP60 value was influenced by factors other than reduced nephron numbers; the contraction of the PSP volume of distribution that occurred after renal mass reduction was one important influencing factor. Overall, the PSP tests more accurately reflected the volume of blood delivered to the kidney than the proximal tubular secretory capacity.

  12. Urinary albumin excretion and its relation with C-reactive protein and the metabolic syndrome in the prediction Of type 2 diabetes

    NARCIS (Netherlands)

    Brantsma, AH; Bakker, SJL; Hillege, HL; De Zeeuw, D; De Jong, PE; Gansevoort, RT

    2005-01-01

    OBJECTIVE - To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEN

  13. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Boesjes, Marije; Wolters, Henk; Bloks, Vincent W; Bos, Trijnie; van Dijk, Theo H; Jurdzinski, Angelika; Boverhof, Renze; Wolters, Justina C; Kuivenhoven, Jan A; van Deursen, Jan M; Oude Elferink, Ronald P J; Moschetta, Antonio; Kremoser, Claus; Verkade, Henkjan J; Kuipers, Folkert; Groen, Albert K

    2017-01-01

    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) cont

  14. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis.

    Science.gov (United States)

    Murunikkara, Vachana; Rasool, Mahaboobkhan

    2014-01-01

    Gout is an inflammatory joint disorder characterized by hyperuricaemia and precipitation of monosodium urate crystals in the joints. In the present study, we aimed to investigate the anti-inflammatory effect of trikatu, a herbal compound in monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and histopathological examination of ankle joints were determined in control and monosodium urate crystal-induced rats. In addition, analgesic (acetic acid-induced writhing response), anti-pyretic (yeast-induced pyrexia) and gastric ulceration effects were tested. The levels of lysosomal enzymes, lipid peroxidation and paw volume were significantly increased, and anti-oxidant status was found to be reduced in monosodium urate crystal-induced rats, whereas the biochemical changes were reverted to near normal levels upon trikatu (1000 mg/kg b.wt) administration. The trikatu has also been found to exhibit significant analgesic and anti-pyretic effects with the absence of gastric damage. In conclusion, the present results clearly indicated that trikatu exert a potent anti-inflammatory effect against monosodium urate crystal-induced inflammation in rats in association with analgesic and anti-pyretic effects in the absence of gastrointestinal damage.

  15. Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease

    Science.gov (United States)

    Mills, Katherine T.; Chen, Jing; Yang, Wei; Appel, Lawrence J.; Kusek, John W.; Alper, Arnold; Delafontaine, Patrice; Keane, Martin G.; Mohler, Emile; Ojo, Akinlolu; Rahman, Mahboob; Ricardo, Ana C.; Soliman, Elsayed Z.; Steigerwalt, Susan; Townsend, Raymond; He, Jiang

    2016-01-01

    IMPORTANCE Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES A composite of CVD events defined as congestive heart failure, stroke, ormyocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09–1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03–1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08–3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD. PMID:27218629

  16. Tophaceous Gout and Renal Insufficiency: A New Solution for an Old Therapeutic Dilemma

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Tausche

    2011-01-01

    Full Text Available The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL. Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (<360 μmol/L. After initial worsening of inflammation in the first weeks, gouty attacks stopped and all tophi resolved within the following 10 months. Renal function remained stable.

  17. Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus.

    Science.gov (United States)

    Murphy, Aisling; Shamshirsaz, Amir; Markovic, Daniela; Ostlund, Richard; Koos, Brian

    2016-03-01

    The effects of gestational diabetes mellitus (GDM) were determined on urinary excretion of putative components of insulin signaling. Random urine samples were collected from 375 gravidas at 6 to 14 weeks' gestation, 22 to 32 weeks' gestation, and ∼6 weeks' postpartum. Gestational diabetes mellitus developed in 35 women who were matched with 59 normal gravidas. Urinary concentrations of myo-inositol (MI) and D-chiro-inositol (DCI) were measured by gas chromatography/mass spectrometry and normalized to creatinine levels. Compared to postpartum values, urinary excretion of MI and DCI was increased 2.9-fold and 2-fold, respectively, in early pregnancy, and 5.5-fold and 4.5-fold, respectively, in later gestation. Gravidas with GDM had significantly greater MI and DCI excretion than controls in the first trimester but not subsequently. The results suggest that gravidas destined to develop GDM have altered synthesis, metabolism, and/or renal excretion of MI and DCI in early pregnancy.

  18. LORRY DRIVERS WORK STRESS EVALUATED BY CATECHOLAMINES EXCRETED IN URINE

    NARCIS (Netherlands)

    VANDERBEEK, AJ; MEIJMAN, TF; FRINGSDRESEN, MHW; KUIPER, JI

    1995-01-01

    Objectives-To evaluate lorry drivers' work stress by measurement of adrenaline and noradrenaline excreted in the urine, and to find out which factors in their working situation are related to the excretion rates of these catecholamines. Methods-The urinary excretion of adrenaline and noradrenaline o

  19. Excretion of polyamines by children with Beckwith's syndrome.

    OpenAIRE

    Barlow, G. B.

    1980-01-01

    The urinary excretion of the polyamines--putrescine, spermidine, and spermine--was measured in 7 children with Beckwith's syndrome. Putrescine excretion was raised and spermidine excretion reduced. The raised putrescine and the low spermidine ratios were highly significant. These results are consistent with a disturbance in a metabolic pathway under growth hormone-like regulation.

  20. Urinary iron excretion test in iron deficiency anemia.

    Directory of Open Access Journals (Sweden)

    Kimura,Ikuro

    1980-02-01

    Full Text Available A urinary iron excretion test was carried out in 22 patients with iron deficiency anemia. The iron excretion index was significantly higher in patients with intractable iron deficiency anemia compared with normal subjects and anemic patients who were responsive to iron therapy. The findings suggest that iron excretion may be a factor that modulates the response of patients to iron therapy.

  1. LORRY DRIVERS WORK STRESS EVALUATED BY CATECHOLAMINES EXCRETED IN URINE

    NARCIS (Netherlands)

    VANDERBEEK, AJ; MEIJMAN, TF; FRINGSDRESEN, MHW; KUIPER, JI

    Objectives-To evaluate lorry drivers' work stress by measurement of adrenaline and noradrenaline excreted in the urine, and to find out which factors in their working situation are related to the excretion rates of these catecholamines. Methods-The urinary excretion of adrenaline and noradrenaline

  2. Prophylaxis on gout flares after the initiation of urate-lowering therapy: a retrospective research

    Science.gov (United States)

    Feng, Xin; Li, Yao; Gao, Wei

    2015-01-01

    The objective of this study was to evaluate the efficacy and safety associated with treatment available to prevent an acute attack of gout when initiating a urate-lowering therapy (ULT). We retrospectively reviewed patients who were diagnosed with gout and treated with ULT during the period from January 2000 to January 2014. They were divided into three groups, 75 patients without prophylaxis treatment, 103 patients treated with etoricoxib, and 129 patients with colchicine treatment. Both demographic and clinical characteristics associated with gout were analyzed. At baseline, demographic and clinical characteristics were generally similar in three groups. SU target level was achieved in 49.3% of the patients without prophylaxis treatment, 66.4% in the etoricoxib group and 65.1% in colchicine group, respectively. During the first 16 weeks, patients without prophylaxis treatment exhibited higher flare rates than patients in other two groups. However, no statistically significant difference was observed between patients in etoricoxib group and colchicine group. In the 16-24 weeks, the proportion of patients who reported flares were all decreased similarly in three groups. The mean number of acute gout flares per patient and gout flare days per patient was significantly higher in patients without prophylaxis treatment than patients in other groups. The mean number of acute gout flares was lower (4.2±2.3 vs 3.2±1.8) in patients with etoricoxib treatment than that in patients with colchicine treatment. Gout flare days per patient were significantly higher in patients without prophylaxis treatment. Compared to colchicine group, gout flare days per patient in etoricoxib were lower (1.2±0.5 vs 2.6±0.6). In term of AEs, patients receiving colchicine had higher rates of gastrointestinal AEs than those who received etoricoxib. In summary, our survey revealed that etoricoxib was more effective and safe than colchicine in preventing acute attack during ULT. PMID:26885092

  3. Therapeutic effects of sesame oil on monosodium urate crystal-induced acute inflammatory response in rats.

    Science.gov (United States)

    Hsu, Dur-Zong; Chen, Si-Jin; Chu, Pei-Yi; Liu, Ming-Yie

    2013-01-01

    Sesame oil has been used in traditional Taiwanese medicine to relieve the inflammatory pain in people with joint inflammation, toothache, scrapes, and cuts. However, scientific evidence related to the effectiveness or action mechanism of sesame oil on relief of pain and inflammation has not been examined experimentally. Here, we investigated the therapeutic effect of sesame oil on monosodium urate monohydrate (MSU) crystal-induced acute inflammatory response in rats. Air pouch, a pseudosynovial cavity, was established by injecting 24 mL of filtered sterile air subcutaneously in the backs of the rats. At day 0, inflammation in air pouch was induced by injecting MSU crystal (5 mg/rat, suspended in sterilized phosphate buffered saline, pH 7.4), while sesame oil (0, 1, 2, or 4 mL/kg, orally) was given 6 h after MSU crystal injection. Parameters in lavage and skin tissue from the air pouches were assessed 6 h after sesame oil was given. Sesame oil decreased MSU crystal-induced total cell counts, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in lavage and pouch tissue. Sesame oil significantly decreased leukocyte and neutrophil counts in lavage compared with MSU crystal alone group. Sesame oil decreased activated mast cell counts in skin tissue in MSU crystal-treated rats. Sesame oil significantly decreased nuclear factor (NF)-κB activity and IL-4 level in isolated mast cells from rats treated with MSU crystal. Furthermore, sesame oil decreased lavage complement proteins C3a and C5a levels in MSU crystal-treated rats. In conclusion, sesame oil shows a potent therapeutic effect against MSU crystal-induced acute inflammatory response in rats.

  4. Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Hegedüs, L; Mathiesen, E R

    1991-01-01

    Forty-seven patients with type 1 (insulin-dependent) diabetes mellitus and 14 normal subjects had renal volume determined by an ultrasonic technique. Renal volume of 299 +/- 49 ml/1.73 m2 (mean +/- SD) in type 1 diabetic patients with normal urinary albumin excretion exceeded that in the normal...... subjects (245 +/- 53 ml/1.73 m2, p less than 0.05). Compared with diabetic patients with normal urinary albumin excretion, renal volume was significantly higher in patients with microalbuminuria (372 +/- 24 ml/1.73 m2, p less than 0.05) and patients with clinical nephropathy (352 +/- 48 ml/1.73 m2, p less...... than 0.05). In a multiple linear regression with HbA1c, urinary albumin excretion, age, diabetes duration and mean blood pressure as independent variables, variations in HbA1c could account for 33% of the variations in kidney volume (n = 47, r = 0.57, p less than 0.01). The other variables played...

  5. Contribution to biorhythm of mercury-excretion

    Energy Technology Data Exchange (ETDEWEB)

    Thiele, H.; Damrau, J.; Franzen, E.; Henkel, W.

    1988-07-01

    The timed urinary mercury-excretion was investigated in 27 formerly exposed. The interval since their last exposure, their age, state of health and duration of exposure differed considerably. Nevertheless a clear circadian rhythm was found by adjustment of mercury to the timed substance-quantity, less to specific gravity, but really not to creatinin. These relations should be considered in biomonitoring. The differences of biorhythm in healthy and mercury-injured persons are discussed.

  6. 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.

  7. Urinary AQP2 excretion is increased during nephrotic syndrome and is associated with reduced urine production

    DEFF Research Database (Denmark)

    Andersen, René Frydensbjerg; Kamperis, Konstantinos; Frøkjær, Jørgen

    of the study was to investigate the urinary presence of the renal water channel AQP2 and it´s correlation to urine production in children with NS. METHODS: A total of 20 (7 girls) children with NS were included with a mean age of 9.1±3.2 yrs. Urine samples were collected from the second morning void at debut......OBJECTIVES: Edema is a hallmark of nephrotic syndrome (NS) and has largely been attributed to sodium retention. Yet low plasma sodium is frequently observed in children with acute NS suggesting that a disturbance in renal water handling may coexist together with sodium retention. The aim......, patients exhibit an increased excretion of AQP2 in urine compared with remission and increased uAQP2 concentration correlated with reduced urine production. Further studies are needed to investigate if uAQP2 contributes to a positive free water balance in NS independently of sodium retention....

  8. PET/Computed Tomography in Renal, Bladder, and Testicular Cancer.

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.

  9. PET/CT in renal, bladder and testicular cancer

    Science.gov (United States)

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

  10. 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.

  11. 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

  12. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

    DEFF Research Database (Denmark)

    Thiesson, Helle; Jensen, Boye L; Bistrup, Claus;

    2007-01-01

    rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining......, and reduced ascites formation to the same degree as direct inhibition of MR with K-canrenoate. Total potassium balance was negative in the BDL rats, whereas renal potassium excretion was unchanged. In the distal colon, expression of ENaC was increased in BDL rats. Fecal potassium excretion was increased...... by endogenous glucocorticoids. In addition, the overall potassium loss in the BDL model is due to increased fecal potassium excretion, which is associated with upregulation of ENaC in distal colon....

  13. 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

  14. 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-

  15. 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

  16. 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.

  17. Renal control of calcium, phosphate, and magnesium homeostasis.

    Science.gov (United States)

    Blaine, Judith; Chonchol, Michel; Levi, Moshe

    2015-07-01

    Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys.

  18. Hypercalcaemia of malignancy: evidence for a nonparathyroid humoral agent with an effect on renal tubular handling of calcium.

    Science.gov (United States)

    Ralston, S H; Fogelman, I; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1984-02-01

    The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

  19. Model for antiorthostatic hypokinesia - Head-down tilt effects on water and salt excretion

    Science.gov (United States)

    Deavers, D. R.; Musacchia, X. J.; Meininger, G. A.

    1980-01-01

    Water and electrolyte excretion was investigated in antiorthostatic hypokinetic and orthostatic hypokinetic and control rats in metabolic cages. Significant (t test, P less than 0.05) diuresis, natriuresis, and kaliuresis occurred in the antiorthostatic hypokinetic subjects but did not occur in either the orthostatic hypokinetic or controls. Recovery from antiorthostatic hypokinesia was characterized by retention of water, sodium, and potassium. Patterns of changes in body weight and food and water consumption were virtually identical in antiorthostatic and orthostatic hypokinetic rats and thus could not account for the differences in renal handling of water and electrolytes. Also, differences in ingestion of food and water in controls could not account for differences in excretion of water and electrolytes between these and antiorthostatic hypokinetic rats. It was concluded that the antiorthostatic position was responsible for the diuresis and natriuresis and that the antiorthostatic hypokinetic rat appears to be a good model for the study of water and elecrolyte excretion during conditions such as bed rest, water immersion, and exposure to weightlessness.

  20. Absorption, metabolism, and excretion of fermented orange juice (poly)phenols in rats.

    Science.gov (United States)

    Escudero-López, Blanca; Calani, Luca; Fernández-Pachón, María-Soledad; Ortega, Angeles; Brighenti, Furio; Crozier, Alan; Del Rio, Daniele

    2014-01-01

    Two milliliters of a fermented, pasteurized orange juice containing ~1% alcohol and 2.3 μmol of (poly)phenolic compounds was fed to rats by gavage after which plasma and urine collected over a 36 h period were analyzed by UHPLC-mass spectrometry. The main constituents in the juice were hesperetin and naringenin-O-glycosides, apigenin-6,8-C-diglucoside, and ferulic acid-4'-O-glucoside. Plasma contained seven flavanone glucuronides, with the principal metabolites, naringenin-7-O-glucuronide, naringenin-4'-O-glucuronide, and an isosakuranetin-O-glucuronide, peaking 6 h after intake at concentrations of ~10 nmol/L. Urinary excretion of four hesperetin glucuronides was equivalent to 0.28% of intake while that of the two naringenin glucuronides was 2.8% of intake. The plasma and urine data suggest that while some absorption occurred in the small intestine, the main site of uptake was the colon. Urine also contained dihydroferulic acid-4'-O-glucuronide and dihydroferulic acid-4'-O-sulfate which were excreted in quantities corresponding to 48.2% of the ingested ferulic acid-4'-glucoside. This indicates that the hydroxycinnamate is much more bioavailable than the flavanones in the rat model. Conversion of the ferulic acid glucoside to the dihydroferulic acid metabolites involves the action of colonic microbial glycosidases and reductases/hydrogenases followed by postabsorption phase II metabolism before renal excretion.

  1. Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in humans.

    Science.gov (United States)

    Buemi, Michele; Di Pasquale, Giuseppe; Ruello, Antonella; Floccari, Fulvio; Aloisi, Carmela; Latassa, Giuseppe; Corsonello, Andrea; Sturiale, Alessio; Corica, Francesco; Frisina, Nicola

    2002-06-01

    The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8 +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue, iloprost, can induce U-AQP2 excretion independent of AVP.

  2. Synthesis of uranyl(II), vanadyl(II) and zirconyl urate complexes, spectral, thermal and biological studies.

    Science.gov (United States)

    El-Megharbel, Samy M; El-Metwaly, Nashwa M; Refat, Moamen S

    2015-01-01

    Three urate chelations were obtained when uric acid was reacted with UO2(CH3COO)2H2O, VOSO4·XH2O and ZrOCl2·XH2O salts with neutralized with 0.1 M NaOH aqueous media. The 1:2 metal-to-ligand complexes [(UO2)2(C5H2N4O3)2](H2O), [(ZrO)2(H2O)2(C5H2N4O3)2] and [VO((C5H3N4O3)2] were characterized by elemental analyses, molar conductivity, (infrared, Raman and UV-vis) spectra, effective magnetic moment in Bohr magnetons, and thermal analysis (TG/DTG). The urate ligand coordinates as mononegative bidentate donor towards the mononuclear central vanadium atom and coordinated as binegative tetradentate mode towards the binuclear dioxouranium and zirconyl centers. The antibacterial activity of the metal complexes were tested against some kind of bacteria and fungi strains and compared with uric acid. The ligand, ZrO(II) and UO2(II) complex showed a week potential degradation on calf thymus DNA, whereas VO(II) complex slightly degraded the DNA.

  3. Intra-articular basic calcium phosphate and monosodium urate crystals inhibit anti-osteoclastogenic cytokine signalling.

    Science.gov (United States)

    Cunningham, C C; Corr, E M; McCarthy, G M; Dunne, A

    2016-12-01

    Basic calcium phosphate (BCP) and monosodium urate (MSU) crystals are particulates with potent pro-inflammatory effects, associated with osteoarthritis (OA) and gout, respectively. Bone erosion, due to increased osteoclastogenesis, is a hallmark of both arthropathies and results in severe joint destruction. The aim of this study was to investigate the effect of these endogenous particulates on anti-osteoclastogenic cytokine signalling. Human osteoclast precursors (OcP) were treated with BCP and MSU crystals prior to stimulation with Interleukin (IL-6) or Interferon (IFN-γ) and the effect on Signal Transducer and Activator of Transcription (STAT)-3 and STAT-1 activation in addition to Mitogen Activated Protein Kinase (MAPK) activation was examined by immunoblotting. Crystal-induced suppressor of cytokine signalling (SOCS) protein and SH-2 containing tyrosine phosphatase (SHP) expression was assessed by real-time polymerase chain reaction (PCR) in the presence and absence of MAPK inhibitors. Pre-treatment with BCP or MSU crystals for 1 h inhibited IL-6-induced STAT-3 activation in human OcP, while pre-treatment for 3 h inhibited IFN-γ-induced STAT-1 activation. Both crystals activated p38 and extracellular signal-regulated (ERK) MAPKs with BCP crystals also activating c-Jun N-terminal kinase (JNK). Inhibition of p38 counteracted the inhibitory effect of BCP and MSU crystals and restored STAT-3 phosphorylation. In contrast, STAT-1 phosphorylation was not restored by MAPK inhibition. Finally, both crystals potently induced the expression of SOCS-3 in a MAPK dependent manner, while BCP crystals also induced expression of SHP-1 and SHP-2. This study provides further insight into the pathogenic effects of endogenous particulates in joint arthropathies and demonstrates how they may contribute to bone erosion via the inhibition of anti-osteoclastogenic cytokine signalling. Potential targets to overcome these effects include p38 MAPK, SOCS-3 and SHP phosphatases

  4. Renal tubular acidosis.

    Science.gov (United States)

    Rothstein, M; Obialo, C; Hruska, K A

    1990-12-01

    Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment

  5. Automated renal histopathology: digital extraction and quantification of renal pathology

    Science.gov (United States)

    Sarder, Pinaki; Ginley, Brandon; Tomaszewski, John E.

    2016-03-01

    The branch of pathology concerned with excess blood serum proteins being excreted in the urine pays particular attention to the glomerulus, a small intertwined bunch of capillaries located at the beginning of the nephron. Normal glomeruli allow moderate amount of blood proteins to be filtered; proteinuric glomeruli allow large amount of blood proteins to be filtered. Diagnosis of proteinuric diseases requires time intensive manual examination of the structural compartments of the glomerulus from renal biopsies. Pathological examination includes cellularity of individual compartments, Bowman's and luminal space segmentation, cellular morphology, glomerular volume, capillary morphology, and more. Long examination times may lead to increased diagnosis time and/or lead to reduced precision of the diagnostic process. Automatic quantification holds strong potential to reduce renal diagnostic time. We have developed a computational pipeline capable of automatically segmenting relevant features from renal biopsies. Our method first segments glomerular compartments from renal biopsies by isolating regions with high nuclear density. Gabor texture segmentation is used to accurately define glomerular boundaries. Bowman's and luminal spaces are segmented using morphological operators. Nuclei structures are segmented using color deconvolution, morphological processing, and bottleneck detection. Average computation time of feature extraction for a typical biopsy, comprising of ~12 glomeruli, is ˜69 s using an Intel(R) Core(TM) i7-4790 CPU, and is ~65X faster than manual processing. Using images from rat renal tissue samples, automatic glomerular structural feature estimation was reproducibly demonstrated for 15 biopsy images, which contained 148 individual glomeruli images. The proposed method holds immense potential to enhance information available while making clinical diagnoses.

  6. Renal effects of methoxyverapamil in anesthetized rats.

    Science.gov (United States)

    Brown, B; Churchill, P

    1983-05-01

    The purpose of these experiments was to determine the renal effects of methoxyverapamil (D-600). Three groups of rats were anesthetized with sodium pentobarbital and given 0, 0.85 or 1.69 nmol/min of methoxyverapamil i.v. Increases in urine flow and Na, K and Ca excretory rates occurred, in an apparently dose-dependent manner. Plasma Na and arterial renin concentration decreased at both doses and, at the higher dose, mean arterial blood pressure and effective renal plasma flow decreased while plasma K increased. Plasma Ca, glomerular filtration rate, filtration fraction and total renal plasma flow were not affected. The findings that methoxyverapamil increased urine flow and electrolyte excretion without changing glomerular filtration rate are consistent with the hypothesis that methoxyverapamil acts directly on tubular reabsorptive mechanisms. These effects, and the effect on plasma renin concentration, could contribute to the beneficial effects of this and other Ca entry antagonists in the treatment of hypertension.

  7. Hormonal regulation of salt and water excretion: a mathematical model of whole kidney function and pressure natriuresis.

    Science.gov (United States)

    Moss, Robert; Thomas, S Randall

    2014-01-01

    We present a lumped-nephron model that explicitly represents the main features of the underlying physiology, incorporating the major hormonal regulatory effects on both tubular and vascular function, and that accurately simulates hormonal regulation of renal salt and water excretion. This is the first model to explicitly couple glomerulovascular and medullary dynamics, and it is much more detailed in structure than existing whole organ models and renal portions of multiorgan models. In contrast to previous medullary models, which have only considered the antidiuretic state, our model is able to regulate water and sodium excretion over a variety of experimental conditions in good agreement with data from experimental studies of the rat. Since the properties of the vasculature and epithelia are explicitly represented, they can be altered to simulate pathophysiological conditions and pharmacological interventions. The model serves as an appropriate starting point for simulations of physiological, pathophysiological, and pharmacological renal conditions and for exploring the relationship between the extrarenal environment and renal excretory function in physiological and pathophysiological contexts.

  8. Creatinine-based estimation of rate of long term renal function loss in lung transplant recipients. Which method is preferable?

    NARCIS (Netherlands)

    Broekroelofs, J; Stegeman, CA; Navis, GJ; de Haan, J; van der Bij, W; de Zeeuw, D; de Jong, PE

    2000-01-01

    Background: Progressive renal function loss during long-term follow up is common after lung transplantation and close monitoring is warranted, Since changes in creatinine generation and excretion may occur after lung transplantation, the reliability of creatinine-based methods of renal function asse

  9. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    Science.gov (United States)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.

  10. Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.

    Science.gov (United States)

    Nagata, Takumi; Suzuki, Masayuki; Fukazawa, Masanori; Honda, Kiyofumi; Yamane, Mizuki; Yoshida, Ayae; Azabu, Hiroko; Kitamura, Hidekazu; Toyota, Naoto; Suzuki, Yoshiyuki; Kawabe, Yoshiki

    2014-06-15

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed a glucose lowering effect in type 2 diabetes patients through inducing renal glucose excretion. Detailed analysis of the mechanism of the glucosuric effect of SGLT2 inhibition, however, has been hampered by limitations of clinical study. Here, we investigated the mechanism of urinary glucose excretion using nonhuman primates with SGLT inhibitors tofogliflozin and phlorizin, both in vitro and in vivo. In cells overexpressing cynomolgus monkey SGLT2 (cSGLT2), both tofogliflozin and phlorizin competitively inhibited uptake of the substrate (α-methyl-d-glucopyranoside; AMG). Tofogliflozin was found to be a selective cSGLT2 inhibitor, inhibiting cSGLT2 more strongly than did phlorizin, with selectivity toward cSGLT2 1,000 times that toward cSGLT1; phlorizin was found to be a nonselective cSGLT1/2 inhibitor. In a glucose titration study in cynomolgus monkeys under conditions of controlled plasma drug concentration, both tofogliflozin and phlorizin increased fractional excretion of glucose (FEG) by up to 50% under hyperglycemic conditions. By fitting the titration curve using a newly introduced method that avoids variability in estimating the threshold of renal glucose excretion, we found that tofogliflozin and phlorizin lowered the threshold and extended the splay in a dose-dependent manner without significantly affecting the tubular transport maximum for glucose (TmG). Our results demonstrate the contribution of SGLT2 to renal glucose reabsorption (RGR) in cynomolgus monkeys and demonstrate that competitive inhibition of cSGLT2 exerts a glucosuric effect by mainly extending splay and lowering threshold without affecting TmG.

  11. Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B(12)

    DEFF Research Database (Denmark)

    Birn, Henrik; Willnow, Thomas E; Nielsen, Rikke;

    2002-01-01

    Megalin has previously been shown to bind and mediate endocytosis of transcobalamin (TC)-B(12). However, the physiological significance of this has not been established, and other TC-B(12) binding proteins have been suggested to mediate renal uptake of this vitamin complex. The present study...... demonstrates by the use of megalin-deficient mice that megalin is, in fact, essential for the normal renal reabsorption of TC-vitamin B(12) and for renal accumulation of this highly conserved vitamin. Megalin-deficient mice excrete increased amounts of TC and B(12) in the urine, revealing a defective renal...... tubular uptake of TC-B(12). The urinary B(12) excretion is increased approximately 4-fold, resulting in an approximately 28-fold higher renal B(12) clearance. This is associated with an approximately 4-fold decrease in B(12) content in megalin-deficient kidney cortex. Thus megalin is important to prevent...

  12. Non-steroidal anti-inflammatory drugs and renal response to exercise

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Jensen, N G; Hansen, J M

    1999-01-01

    at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone....... Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed...... baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin...

  13. Nickel Excretion in Urine after Oral Administration

    DEFF Research Database (Denmark)

    Menne, T.; Mikkelsen, H. I.; Solgaard, Per Bent

    1978-01-01

    In recent years the importance of internal exposure to nickel in patients with recurrent hand eczema and nickel allergy has become evident. The present study was performed in order to investigate the value of urinary nickel determinations as an index of oral nickel intake. After oral administration...... of 5.6 mg nickel (as the sulfate), increased nickel excretion was found over the following 2-3 days. We conclude that consecutive urinary nickel determinations are able to disclose variations in oral intake of nickel....

  14. Myoclonus in renal failure: Two cases of gabapentin toxicity

    Directory of Open Access Journals (Sweden)

    Kenneth R. Kaufman

    2014-01-01

    Full Text Available Gabapentin, an AED approved for the adjunctive treatment of partial seizures with/without secondary generalization and for the treatment of postherpetic neuralgia, is frequently used off-label for the treatment of both psychiatric and pain disorders. Since gabapentin is cleared solely by renal excretion, dosing requires consideration of the patient's renal function. Myoclonic activity may occur as a complication of gabapentin toxicity, especially with acute kidney injury or end-stage renal disease. We report 2 cases of myoclonic activity associated with gabapentin toxicity in the setting of renal disease which resolved with discontinuation of gabapentin and treatment with hemodialysis and peritoneal dialysis. As gabapentin has multiple indications and off-label uses, an understanding of myoclonus, neurotoxicity, and renal dosing is important to clinicians in multiple specialties.

  15. Urinary sodium excretion and kidney failure in nondiabetic chronic kidney disease.

    Science.gov (United States)

    Fan, Li; Tighiouart, Hocine; Levey, Andrew S; Beck, Gerald J; Sarnak, Mark J

    2014-09-01

    Current guidelines recommend under 2 g/day sodium intake in chronic kidney disease, but there are a few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-h urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-h urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 participants, and the composite outcome was reached in 723. In the primary analyses, there was no association between 24-h urine sodium and kidney failure (HR 0.99 (95% CI 0.91-1.08)) nor on the composite outcome (HR 1.01 (95% CI 0.93-1.09)), each per 1 g/day higher urine sodium. In exploratory analyses, there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a two-slope model, when urine sodium was under 3 g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1 g/day and with lower risk of kidney failure in those with baseline proteinuria of ⩾ 1 g/day. There was no association between urine sodium and kidney failure when urine sodium was ⩾ 3 g/day. Results were consistent using first baseline and time-dependent urinary sodium excretion. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored.

  16. Effects of Berberine on NLRP3 and IL-1β Expressions in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

    Science.gov (United States)

    Wen, Cai-Yu-Zhu; Chen, Zhe; Wang, Yu; Huang, Ying

    2016-01-01

    Background. Urate crystals-induced inflammation is a critical factor during the initiation of gouty arthritis. Berberine is well known for its anti-inflammatory activity. However, the underlying effects of berberine on monosodium urate crystals-induced inflammation remain obscure. Objectives. This study is set to explore the protective effect and mechanism of berberine on monosodium urate crystals-induced inflammation in human monocytic THP-1 cells. Methods. The mRNA levels of NLRP3 and IL-1β were measured by Real-Time PCR, and the protein levels of NLRP3 and IL-1β were determined by ELISA, Western blot, and immunofluorescence. Results. The NLRP3 and IL-1β expressions were significantly increased in model group compared to that in normal group (P < 0.05). Meanwhile, there was significant reduction in the expressions of NLRP3 and IL-1β mRNA in groups 6.25 μM berberine and 25 μM berberine when compared with model group (P < 0.05). Conclusions. Therefore, berberine alleviates monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL-1β expressions. The regulatory effects of berberine may be related to the inactivation of NLRP3 inflammasome. PMID:27689075

  17. Effects of Berberine on NLRP3 and IL-1β Expressions in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Ya-Fei Liu

    2016-01-01

    Full Text Available Background. Urate crystals-induced inflammation is a critical factor during the initiation of gouty arthritis. Berberine is well known for its anti-inflammatory activity. However, the underlying effects of berberine on monosodium urate crystals-induced inflammation remain obscure. Objectives. This study is set to explore the protective effect and mechanism of berberine on monosodium urate crystals-induced inflammation in human monocytic THP-1 cells. Methods. The mRNA levels of NLRP3 and IL-1β were measured by Real-Time PCR, and the protein levels of NLRP3 and IL-1β were determined by ELISA, Western blot, and immunofluorescence. Results. The NLRP3 and IL-1β expressions were significantly increased in model group compared to that in normal group (P<0.05. Meanwhile, there was significant reduction in the expressions of NLRP3 and IL-1β mRNA in groups 6.25 μM berberine and 25 μM berberine when compared with model group (P<0.05. Conclusions. Therefore, berberine alleviates monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL-1β expressions. The regulatory effects of berberine may be related to the inactivation of NLRP3 inflammasome.

  18. Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

    Science.gov (United States)

    Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem

    2017-08-31

    Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 2017. © 2017 Wiley Periodicals, Inc.

  19. Enhanced interleukin-1beta production of PBMCs from patients with gout after stimulation with Toll-like receptor-2 ligands and urate crystals

    NARCIS (Netherlands)

    Mylona, E.E.; Mouktaroudi, M.; Crisan, T.O.; Makri, S.; Pistiki, A.; Georgitsi, M.; Savva, A.; Netea, M.G.; Meer, J.W. van der; Giamarellos-Bourboulis, E.J.; Joosten, L.A.B.

    2012-01-01

    ABSTRACT: INTRODUCTION: Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using hu

  20. Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1 beta by mononuclear cells through a caspase 1-mediated process.

    NARCIS (Netherlands)

    Giamarellos, E.J.; Mouktaroudi, M.; Bodar, E.J.; Ven, J. van de; Kullberg, B.J.; Netea, M.G.; Meer, J.W.M. van der

    2009-01-01

    OBJECTIVE: Recent studies suggest that crystals of monosodium urate (MSU), deposited in joints of patients with acute gouty arthritis, activate the NACHT domain, leucine-rich repeat and pyrin domain-containing protein (NALP)3 inflammasome. In the present study we have investigated whether production

  1. Dual-Energy Computed Tomography of the Knee, Ankle, and Foot: Noninvasive Diagnosis of Gout and Quantification of Monosodium Urate in Tendons and Ligaments.

    Science.gov (United States)

    Fritz, Jan; Henes, Joerg C; Fuld, Matthew K; Fishman, Elliot K; Horger, Marius S

    2016-02-01

    Gout is a true crystal deposition arthropathy caused by the precipitation of monosodium urate into joints and periarticular soft tissues. It is the most common inflammatory arthropathy in men and women of older age with a male-to-female ratio of 3 to 8:1. The disease may progress from asymptomatic hyperuricemia through symptomatic acute gout attacks with asymptomatic periods into chronic symptomatic tophaceous gout. Although invasive arthrocentesis and demonstration of monosodium urate crystals on polarized light microscopy is definitive for the diagnosis of gout, dual-energy computed tomography (CT) allows for noninvasive visualization and reproducible volume quantification of monosodium urate crystals. Based on the high diagnostic performance, dual-energy CT has been included in the 2015 American College of Rheumatology/European League Against Rheumatism Collaborative Initiative Classification Criteria for Gout. Increasing evidence indicates the usefulness of dual-energy CT to guide the management of patients with suspected gout and monitor the effectiveness of urate-lowering medical therapy.

  2. Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans

    Energy Technology Data Exchange (ETDEWEB)

    McConnell, J.D.; Sagalowsky, A.I.; Lewis, S.E.; Gailiunas, P.; Helderman, J.H.; Dawidson, I.; Peters, P.C.

    1984-05-01

    A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

  3. Transient receptor potential vanilloid 1 activation by dietary capsaicin promotes urinary sodium excretion by inhibiting epithelial sodium channel α subunit-mediated sodium reabsorption.

    Science.gov (United States)

    Li, Li; Wang, Fei; Wei, Xing; Liang, Yi; Cui, Yuanting; Gao, Feng; Zhong, Jian; Pu, Yunfei; Zhao, Yu; Yan, Zhencheng; Arendshorst, William J; Nilius, Bernd; Chen, Jing; Liu, Daoyan; Zhu, Zhiming

    2014-08-01

    High salt (HS) intake contributes to the development of hypertension. Epithelial sodium channels play crucial roles in regulating renal sodium reabsorption and blood pressure. The renal transient receptor potential vanilloid 1 (TRPV1) cation channel can be activated by its agonist capsaicin. However, it is unknown whether dietary factors can act on urinary sodium excretion and renal epithelial sodium channel (ENaC) function. Here, we report that TRPV1 activation by dietary capsaicin increased urinary sodium excretion through reducing sodium reabsorption in wild-type (WT) mice on a HS diet but not in TRPV1(-/-) mice. The effect of capsaicin on urinary sodium excretion was involved in inhibiting αENaC and its related with-no-lysine kinase 1/serum- and glucocorticoid-inducible protein kinase 1 pathway in renal cortical collecting ducts of WT mice. Dietary capsaicin further reduced the increased αENaC activity in WT mice attributed to the HS diet. In contrast, this capsaicin effect was absent in TRPV1(-/-) mice. Immunoprecipitation study indicated αENaC specifically coexpressed and functionally interact with TRPV1 in renal cortical collecting ducts of WT mice. Additionally, ENaC activity and expression were suppressed by capsaicin-mediated TRPV1 activation in cultured M1-cortical collecting duct cells. Long-term dietary capsaicin prevented the development of high blood pressure in WT mice on a HS diet. It concludes that TRPV1 activation in the cortical collecting ducts by capsaicin increases urinary sodium excretion and avoids HS diet-induced hypertension through antagonizing αENaC-mediated urinary sodium reabsorption. Dietary capsaicin may represent a promising lifestyle intervention in populations exposed to a high dietary salt intake.

  4. 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 ...

  5. 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.

  6. 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.

  7. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Science.gov (United States)

    Amaral, Nathalia O; de Oliveira, Thiago S; Naves, Lara M; Filgueira, Fernando P; Ferreira-Neto, Marcos L; Schoorlemmer, Gerard H M; de Castro, Carlos H; Freiria-Oliveira, André H; Xavier, Carlos H; Colugnati, Diego B; Rosa, Daniel A; Blanch, Graziela T; Borges, Clayton L; Soares, Célia M A; Reis, Angela A S; Cravo, Sergio L; Pedrino, Gustavo R

    2014-01-01

    Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  8. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

    Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  9. Salt restriction inhibits renal growth and stabilizes injury in rats with established renal disease.

    Science.gov (United States)

    Dworkin, L D; Benstein, J A; Tolbert, E; Feiner, H D

    1996-03-01

    Salt restriction inhibits renal growth and stabilizes injury in rats with established renal disease. Male Munich-Wistar rats that underwent right nephrectomy and segmental infarction of two thirds of the left kidney were fed standard chow for 4 wk and then randomly assigned to ingest standard or low-salt chow for an additional 4 wk. Four wk after ablation, rats had systemic hypertension, proteinuria, and glomerular sclerosis. The prevalence of sclerosis, protein excretion rate, and glomerular volume increased between the fourth and eighth week in rats that were fed standard chow, however, in rats that were fed low-salt chow, the increase in glomerular volume and development of further glomerular sclerosis was prevented whereas the protein excretion rate actually declined. Micropuncture studies performed 8 wk after ablation revealed that the glomerular hydraulic pressure was elevated in remnant kidneys and was not affected by salt restriction. This study demonstrates that dietary salt restriction can prevent further glomerular injury and reduce proteinuria even when instituted in rats with established renal disease. These findings are also consistent with the hypothesis that glomerular hypertrophy promotes injury in this model of hypertension and progressive renal disease.

  10. The Role of Matrix Metalloproteinases in Renal Diseases

    Directory of Open Access Journals (Sweden)

    Funda SAĞLAM

    2011-05-01

    Full Text Available Matrix metalloproteinases (MMPs are a family of zinc dependent proteinases and the main promoters of extracellular matrix degradation. Their role in renal diseases is now being understood better. Several progressive renal diseases are characterized with persistent cell proliferation and abnormal production of extracellular matrix by mesengial cells. Understanding mesengial cell proliferation and the factors regulating extracellular matrix metabolism is therefore becoming more important. MMPs have been shown to be produced and excreted from renal glomerular cells and interstitital fibroblast and tubuloepithelial cells have also been shown to excrete MMPs. MMPs function in expansive cell behaviour, embryonic evolution and tissue fibrosis. Production of MMPs are known to increase in inflammation and restructure processes. Data obtained from both experimental and clinical studies has shown the role of MMPs in proliferative glomerulonephritis, hypertensive nephropathy, diabetic nephropathy, HIV nephropathy, toxic nephropathy, obstructive nephropathy, renal cell carcinoma, chronic allograft nephropathy-related fibrosis and in many other renal diseases. In light of these data, therapy options targeting MMPs have become a current issue. Limited data obtained from recent studies are promising about the clinical use of therapies repressing MMPs in future. The roles of MMPs which increase in inflammation and restructure processes in renal diseases and future therapy options are discussed in this review.

  11. Hyporeninemic hypoaldosteronism in diabetic patients with chronic renal failure.

    Science.gov (United States)

    Grande Villoria, J; Macias Nunez, J F; Miralles, J M; De Castro del Pozo, S; Tabernero Romo, J M

    1988-01-01

    Plasma renin activity, plasma aldosterone levels and renal tubular capacity to excrete hydrogen ions were studied in 13 patients suffering from diabetes mellitus with a creatinine clearance of less than 40 ml/min. The results were compared with those obtained in a control group, in a group of nondiabetic subjects with chronic renal failure (CRF) and in a group of diabetic patients without CRF. Twelve of the thirteen diabetic patients with CRF had data characteristic of hyporeninemic hypoaldosteronism associated with type IV renal tubular acidosis. On comparing the results with those of the other two groups of patients, it was observed that the manifestations of the latter two groups considered separately were different from those of the problem group, although in the diabetic patients with normal glomerular filtration rate (GFR) hyporeninism but not hypoaldosteronism was present accompanied by a lower net acid excretion (p less than 0.001) due to a lower excretion of NH4 (p less than 0.05) and titratable acid (p less than 0.001) when the patients were challenged with an NH4Cl overload. We believe that a conjunction of diabetes and renal failure is necessary for the diabetic patients with a decrease in GFR to show hyporeninemic hypoaldosteronism and type IV tubular acidosis.

  12. 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.)

  13. Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression.

    Science.gov (United States)

    Kim, Hye-Young; Baylis, Chris; Verlander, Jill W; Han, Ki-Hwan; Reungjui, Sirirat; Handlogten, Mary E; Weiner, I David

    2007-10-01

    Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na(+) and K(+) were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass.

  14. Excreción de promastigotos de Leishmania pifanoi por Lutzomyia youngi experimentalmente infectada Excretion of promastigotos of Leishmania pifanoi by experimentally infected Lutzomyia youngi

    Directory of Open Access Journals (Sweden)

    Elina Rojas

    1995-12-01

    drops excreted react positively to glucose or contain crystals of urate. The excess promastigotes of the second stage of development are eliminated in the last excretions and react positively to the Hemoscreen and Biuret tests for total proteins as also for glucose and account for 82% of the of drops excreted. The excretion of parasites by Lu. youngi is a normal stage in the growth of L. pifanoi into a vector.

  15. Mendelian randomization provides no evidence for a causal role of serum urate in increasing serum triglyceride levels.

    Science.gov (United States)

    Rasheed, Humaira; Hughes, Kim; Flynn, Tanya J; Merriman, Tony R

    2014-12-01

    Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to test for a causal role of SU in increasing triglyceride using Mendelian randomization that accounts for unmeasured confounding. Subjects were of European ancestry from the atherosclerosis risk in communities (n=5237) and Framingham heart (n=2971) studies. Mendelian randomization by the 2-stage least squares regression method was done with SU as the exposure, a uric acid transporter genetic risk score as instrumental variable, and triglyceride as the outcome. In ordinary linear regression, SU was significantly associated with triglyceride levels (β=2.69 mmol/L change in triglyceride per mmol/L increase in SU). However, Mendelian randomization-based estimation showed no evidence for a direct causal association of SU with triglyceride concentration-there was a nonsignificant 1.01 mmol/L decrease in triglyceride per mmol/L increase in SU attributable to the genetic risk score (P=0.21). The reverse analysis using a triglyceride genetic risk score provided evidence of a causal role for triglyceride in raising urate in men (P(Corrected)=0.018). These data provide no evidence for a causal role for SU in raising triglyceride levels, consistent with a previous Mendelian randomization report of no association between SU and ischemic heart disease. © 2014 American Heart Association, Inc.

  16. Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Ahmed A. Elmarakby

    2012-01-01

    Full Text Available The renoprotective mechanisms of hemeoxygenase-1 (HO-1 in diabetic nephropathy remain to be investigated. We hypothesize that HO-1 protects the kidney from diabetic insult via lowering renal oxidative stress and inflammation. We used control and diabetic SHR with or without HO-1 inducer cobalt protoporphyrin (CoPP treatment for 6 weeks. Urinary albumin excretion levels were significantly elevated in diabetic SHR compared to control and CoPP significantly attenuated albumin excretion. Immuno-histochemical analysis revealed an elevation in TGF-β staining together with increased urinary collagen excretion in diabetic versus control SHR, both of which were reduced with CoPP treatment. Renal oxidative stress markers were greater in diabetic SHR and reduced with CoPP treatment. The increase in renal oxidative stress was associated with an elevation in renal inflammation in diabetic SHR. CoPP treatment also significantly attenuated the markers of renal inflammation in diabetic SHR. In vitro inhibition of HO with stannous mesoporphyrin (SnMP increased glomerular NADPH oxidase activity and inflammation and blocked the anti-oxidant and anti-inflammatory effects of CoPP. These data suggest that the reduction of renal injury in diabetic SHR upon induction of HO-1 are associated with decreased renal oxidative stress and inflammation, implicating the role of HO-1 induction as a future treatment of diabetic nephropathy.

  17. Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoarthritis.

    Science.gov (United States)

    Cangiano, J L; Figueroa, J; Palmer, R

    1999-03-01

    We assessed the effects of nabumetone, sulindac, and placebo on renal function and renal excretion of vasodilatory prostaglandins in older female patients (age >50 years) with osteoarthritis and normal renal function. Using a prospective, crossover design, we compared the effects of nabumetone 2000 mg/d and sulindac 400 mg/d with placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1alpha in 12 patients. Urinary excretion of vasodilatory prostaglandins was not decreased after 14 days of treatment with either nabumetone or sulindac. Likewise, treatment with nabumetone or sulindac did not significantly alter renal function compared with placebo. There were no differences in mean changes in GFR or RPF from baseline after treatment with nabumetone or sulindac compared with placebo. The mean (+/- SD) changes in GFR from baseline were 0%+/-8% in patients receiving nabumetone, -8%+/-15% in patients receiving sulindac, and -7%+/-15% in patients receiving placebo. The results of this study demonstrate that treatment with nabumetone or sulindac caused no deterioration in renal function in older female patients with osteoarthritis and normal renal function.

  18. Evidence Report: Risk of Renal Stone Formation

    Science.gov (United States)

    Sibonga, Jean D.; Pietrzyk, Robert

    2017-01-01

    The formation of renal stones poses an in-flight health risk of high severity, not only because of the impact of renal colic on human performance but also because of complications that could potentially lead to crew evacuation, such as hematuria, infection, hydronephrosis, and sepsis. Evidence for risk factors comes from urine analyses of crewmembers, documenting changes to the urinary environment that are conducive to increased saturation of stone-forming salts, which are the driving force for nucleation and growth of a stone nidus. Further, renal stones have been documented in astronauts after return to Earth and in one cosmonaut during flight. Biochemical analysis of urine specimens has provided indication of hypercalciuria and hyperuricemia, reduced urine volumes, and increased urine saturation of calcium oxalate and calcium phosphate. A major contributor to the risk for renal stone formation is bone atrophy with increased turnover of the bone minerals. Dietary and fluid intakes also play major roles in the risk because of the influence on urine pH (more acidic) and on volume (decreased). Historically, specific assessments on urine samples from some Skylab crewmembers indicated that calcium excretion increased early in flight, notable by day 10 of flight, and almost exceeded the upper threshold for normal excretion (300mg/day in males). Other crewmember data documented reduced intake of fluid and reduced intake of potassium, phosphorus, magnesium, and citrate (an inhibitor of calcium stone formation) in the diet. Hence, data from both short-duration and long-duration missions indicate that space travel induces risk factors for renal stone formation that continue to persist after flight; this risk has been documented by reported kidney stones in crewmembers.

  19. 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...

  20. Reduced fecal sterol excretion in subjects with familial hypoalphalipoproteinemia

    NARCIS (Netherlands)

    El Harchaoui, Karim; Franssen, Remco; Hovingh, G. Kees; Bisoendial, Radjesh J.; Stellaard, Frans; Kuipers, Folkert; Kastelein, John J. P.; Kuivenhoven, Jan Albert; Stroes, Erik S. G.; Groen, Albert K.

    2009-01-01

    BACKGROUND: Fecal bile acid and neutral sterol excretion are the obligate endpoints of the reverse cholesterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-cholesterol (HDL-c) levels and fecal sterol excretion. In this study, we have evaluated this re

  1. Urinary, biliary and faecal excretion of rocuronium in humans

    NARCIS (Netherlands)

    Proost, JH; Eriksson, LI; Mirakhur, RK; Wierda, JMKH

    2000-01-01

    The excretion of rocuronium and its potential metabolites was studied in 38 anaesthetized patients, ASA I-III and 21-69 yr old. Rocuronium bromide was administered as an i.v. bolus dose of 0.3 or 0.9 mg kg(-1). in Part A of the study, the excretion into urine and bile, and the liver content were stu

  2. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy.

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Carmosino, Monica; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto; Procino, Giuseppe

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  3. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Luigi Rossi

    2017-01-01

    Full Text Available Diabetic nephropathy (DN is a microangiopathic complication of diabetes mellitus (DM affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs, expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2, via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM, 11 with proteinuric nondiabetic nephropathy (NDN, and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  4. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN. PMID:28246612

  5. The renal effects of NSAIDs in dogs.

    Science.gov (United States)

    Lomas, Amy L; Grauer, Gregory F

    2015-01-01

    The quality of life for dogs with osteoarthritis can often be improved with nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse drug events associated with NSAID use reported to the Federal Drug Administration Center for Veterinary Medicine is higher than that for any other companion animal drug. Of those events, adverse renal reactions are the second most reported. NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX), which decreases production of prostanoids. Prostaglandins are synthesized by both the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow, glomerular filtration rate, renin release, and Na excretion. There are important species differences in the renal expression of COX-1 and COX-2. For example, dogs have higher basal levels of COX-2 expression in the kidney compared with humans. In addition, in dogs with chronic kidney disease, an increase in COX-2 expression occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those reasons, NSAIDs that target COX-2 may be expected to adversely affect renal function in dogs, especially dogs with chronic kidney disease. The purpose of this review was to evaluate the literature to report the renal effects of NSAIDs in dogs.

  6. 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...

  7. 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.

  8. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  9. 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

  10. 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

  11. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

    Science.gov (United States)

    Torres, V E; Wilson, D M; Burnett, J C; Johnson, C M; Offord, K P

    1991-10-01

    We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.

  12. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M H; Olsen, Niels Vidiendal; Christensen, P

    1999-01-01

    Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7......-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood...... urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 +/- 17 micrograms/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (...

  13. Cardiovascular, endocrine and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M.H.; Olsen, N.V.; Christensen, P.

    1999-01-01

    Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7......-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood...... urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 +/- 17 micrograms/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (

  14. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia.

    Science.gov (United States)

    Jefferson, J Ashley; Escudero, Elizabeth; Hurtado, Maria-Elena; Kelly, Jackeline Pando; Swenson, Erik R; Wener, Mark H; Burnier, Michel; Maillard, Marc; Schreiner, George F; Schoene, Robert B; Hurtado, Abdias; Johnson, Richard J

    2002-06-01

    Chronic exposure to high altitude is associated with the development of erythrocytosis, proteinuria, and, in some cases, hyperuricemia. We examined the relationship between high-altitude polycythemia and proteinuria and hyperuricemia in Cerro de Pasco, Peru (altitude, 4,300 m). We studied 25 adult men with hematocrits less than 65% and 27 subjects with excessive erythrocytosis (EE; hematocrit > 65%) living in Cerro de Pasco, Peru and compared them with 28 control subjects living in Lima, Peru (at sea level) and after 48 hours of exposure to high altitude. Serum urate levels were significantly elevated in patients with EE at altitude, and gout occurred in 4 of 27 of these subjects. Urate level strongly correlated with hematocrit (r = 0.71; P < 0.0001). Urate production (24-hour urine urate excretion and urine urate-creatinine ratio) was increased in this group compared with those at sea level. Fractional urate excretion was not increased, and fractional lithium excretion was reduced, in keeping with increased proximal reabsorption of filtrate. Significantly higher blood pressures and decreased renin levels in the EE group were in keeping with increased proximal sodium reabsorption. Serum urate levels correlated with mean blood pressure (r = 0.50; P < 0.0001). Significant proteinuria was more prevalent in the EE group despite normal renal function. Hyperuricemia is common in subjects living at high altitude and associated with EE, hypertension, and proteinuria. The increase in uric acid levels appears to be caused by increased urate generation secondary to systemic hypoxia, although a relative impairment in renal excretion also may contribute.

  15. CINACALCET IN TREATMENT OF HYPERPARATHYROIDISM IN RECIPIENTS OF RENAL GRAFT

    Directory of Open Access Journals (Sweden)

    O. N. Vetchinnikova

    2014-01-01

    Full Text Available Aim. Evaluate the efficacy and safety of cinacalcet in the treatment of hyperparathyroidism (HPT in renal transplant recipients. Materials and methods. During the year, three patients with satisfactory functioning kid- ney transplant (glomerular filtration rate − GFR 44–80 ml/min and HPT (parathyroid hormone − PTH 320– 348 pg/ml, resistant to treatment with active forms of vitamin D and hypercalcemia (2,6–3,1 mmol/l were treated with cinacalcet (initial dose of 30 mg/day, supporting − 60–15 mg/day with the added in 2–3 months alfacalcidol (0,25–0,75 μg/day. Investigated the serum concentrations and renal excretion of calcium and phos- phorus, PTH, renal transplant function (blood creatinine, GFR, plasma concentrations of tacrolimus, bone mine- ral density (BMD in different parts of the skeleton (dual energy X-ray absorptiometry. Results. A month later, the level of calcium in the blood to normal, PTH levels decreased by 1,2–3,2 times. A year later, in two patients, blood levels of PTH was back to normal, one − up − 142 pg/ml. Renal excretion of calcium varied differently − in two patients increased gradually, without exceeding the physiological norm, and in one − remained stable. Gene- ral pattern in the dynamics of serum concentration and urinary excretion of phosphorus was not observed. Renal graft function remained stable − GFR 46–76 ml/min. BMD of the distal forearm, femoral neck and lumbar spine in two patients remained the same, in one − increased by 14, 6 and 7%. Adverse events were absent. Conclusion. Application of cinacalcet is promising for the correction of HPT in renal transplant recipients. 

  16. Acute renal failure after ingestion of guaifenesin and dextromethorphan.

    Science.gov (United States)

    Small, Evan; Sandefur, Benjamin J

    2014-07-01

    Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The renal handling of hemoglobin. I. Glomerular filtration.

    Science.gov (United States)

    Bunn, H F; Esham, W T; Bull, R W

    1969-05-01

    The glomerular filtration of hemoglobin (alpha(2)beta(2)) was studied under conditions in which its dissociation into alphabeta dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of (59)Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.

  18. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    Science.gov (United States)

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.

  19. 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....

  20. 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.

  1. Influence of dietary protein on renal function in dogs.

    Science.gov (United States)

    Bovée, K C

    1991-11-01

    Two previously published studies in dogs with reduced renal function are reviewed. In the first study, renal function and biochemical responses to dietary changes were studied in four dogs with stable chronic renal failure. The objective was to determine if dogs with moderate stable failure adjust to diets with varied protein and electrolyte content. These dogs were found to have the capacity to adapt to a wide range of dietary protein and electrolyte intake. The only exception was found in dogs fed a reduced-protein diet, which failed to appropriately adjust renal tubular excretion of sodium and phosphate. The only advantage of reduced dietary protein in this study was a reduction in blood urea nitrogen (BUN). Disadvantages of reduced-protein diets were reduced glomerular filtration rate (GFR) and renal plasma flow. In the second study, the hypothesis that large amounts of dietary protein sustain renal hyperfunction and produce progressive glomerulosclerosis in dogs as previously reported in rats was tested. Results failed to find a pattern of deterioration of renal function over 4 y. Light microscopic changes and electron microscopy also failed to find glomerular injury similar to that reported in rodents. These results do not support the hypothesis that feeding a high protein diet had a significant adverse effect on renal function or morphology.

  2. 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 ...

  3. Excretion of biliary compounds during intrauterine life

    Science.gov (United States)

    Macias, Rocio IR; Marin, Jose JG; Serrano, Maria A

    2009-01-01

    In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem. PMID:19230042

  4. Excretion of biliary compounds during intrauterine life

    Institute of Scientific and Technical Information of China (English)

    Rocio IR Macias; Jose JG Marin; Maria A Serrano

    2009-01-01

    In adults, the hepatobiliary system, together with thekidney, constitute the main routes for the eliminationof several endogenous and xenobiotic compounds intobile and urine, respectively. However, during intrauterinelife the biliary route of excretion for cholephiliccompounds, such as bile acids and biliary pigments, isvery poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

  5. Excretion of drugs in human breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Welch, R.M.; Findlay, J.W.

    1981-01-01

    The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.

  6. Urinary growth hormone excretion in 657 healthy children and adults

    DEFF Research Database (Denmark)

    Main, K; Philips, M; Jørgensen, M

    1991-01-01

    Urinary growth hormone (u-GH) excretion was measured in 547 healthy children and 110 adults by ELISA with a detection limit of 1.1 ng/l u-GH after prior concentration of the urine samples (20- to 30-fold). u-GH excretion values were significantly dependent on the pubertal stage (p less than 0.......0001) with maximum values in Tanner stage 3 for girls and 4 for boys. This corresponded to a peak in u-GH excretion between 11.5-14.5 years in girls and 12.5-16 years in boys. Additionally, u-GH excretion in adults was significantly higher than in prepubertal children (p less than 0.001). The day/night ratio of u...... in nanograms per gram creatinine did not diminish the observed variation and blunted the pubertal increase in u-GH excretion. In conclusion, (1) u-GH excretion depends significantly on age, sex and pubertal maturation as does the day/night ratio of u-GH excretion. (2) The interindividual variation in u...

  7. Determination of Lead in Human Calculi and Its Effects on Renal Function of Lead Occupational Workers

    Directory of Open Access Journals (Sweden)

    F. Memon

    2016-06-01

    Full Text Available Seventy five samples of renal and eighteen samples of supra gingival calculi of lead recycling workers were collected over the period of seven years (2008-2014 and studied for the accumulation of lead. The results were compared with those of non exposed subjects. The lead content of calculi was investigated for its dependence on type and composition of calculi, blood lead, job status and duration of exposure. The effect of blood lead and renal calculi was also investigated in relation to kidney function of respective subjects. The mean lead levels of various types of calculi were found to follow the order as phosphate > oxalate > urate .> cystine while single principal group of supra gingival calculi resulted in lower levels of metal. The lead content of calculi positively correlated with phosphate content of both of the renal (r = 0.655 and supra gingival calculi (r= 0.866, Impaired renal function was more pronounced in active workers and depended on blood lead levels in addition to presence of metal in renal calculi

  8. Dual energy computed tomography for quantification of tissue urate deposits in tophaceous gout: help from modern physics in the management of an ancient disease.

    Science.gov (United States)

    Bacani, A Kirstin; McCollough, Cynthia H; Glazebrook, Katrina N; Bond, Jeffrey R; Michet, Clement J; Milks, Jeffrey; Manek, Nisha J

    2012-01-01

    Gout has been recognized for centuries but is also a modern day scourge. It is the most common type of inflammatory arthritis in men and appears to be increasing in both incidence and prevalence (Arromdee et al. in J Rheumatol 29(11):2403-2406, 2002). Despite these facts, few advances have been made in the diagnosis and treatment of gout for over 50 years. Difficult cases of gout challenge available therapeutic options. It is only recently that the Food and Drug Administration has approved febuxostat as a treatment option for patients intolerant of allopurinol. We describe a difficult case of tophaceous gout notable for several reasons: utilization of rasburicase as uricolytic treatment to dramatically reduce tissue urate burden; treatment of gout flares with interleukin-1β inhibition; and quantification of tissue urate with novel dual energy computed tomography technology before and after uricolytic therapy.

  9. Association of urine protein excretion and infection with Borrelia burgdorferi sensu lato in Bernese Mountain dogs.

    Science.gov (United States)

    Gerber, Bernhard; Eichenberger, Simone; Haug, Katharinan; Wittenbrink, Max M; Reusch, Claudia E

    2009-12-01

    Bernese Mountain dogs (BMDs) are prone to develop a familial glomerulonephropathy and a pathogenic role of Borrelia burgdorferi sensu lato in this disease has been suspected. Glomerular disease in many affected dogs is clinically inapparent and proteinuria is found incidentally. In this study, urine protein excretion was evaluated in 122 clinically healthy BMDs and 55 controls. The seroprevalence of B. burgdorferi in BMDs was 57%, compared to 16% in controls. There were no significant differences in the occurrence of positive dipstick results, microalbuminuria, urine protein-to-urine creatinine ratio or abnormal urine protein pattern (determined by sodium dodecyl sulphate agarose gel electrophoresis) between BMDs and controls and BMDs with and without antibodies against B. burgdorferi. It was concluded that antibodies against B. burgdorferi are not associated with proteinuria as an early sign of renal disease in BMDs.

  10. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

    DEFF Research Database (Denmark)

    Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin

    2009-01-01

    BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker...... candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1...... and type 2 diabetes, respectively. Most were normotensive, and all had normoalbuminuria (median urinary albumin excretion rate, 5.0 microg/min). INTERVENTION: Candesartan, 16 mg/d increasing to 32 mg/d, versus placebo. Assignment was done centrally using an interactive voice-response system. Patients...

  11. The mechanism of excretion of trientine from the rat kidney: trientine is not recognized by the H+/organic cation transporter.

    Science.gov (United States)

    Kobayashi, M; Tanabe, R; Sugawara, M; Iseki, K; Miyazaki, K

    1997-04-01

    Trientine dihydrochloride is used to treat Wilson's disease by chelating copper and increasing its urinary excretion. The mechanism of renal excretion of trientine has been investigated in-vivo and in-vitro. Trientine clearance in the rat-was significantly faster than creatinine clearance. When trientine and the same number of moles of copper ions were administered simultaneously to the rat, however, trientine clearance decreased to almost the same level as the creatinine clearance. To clarify this active excretion system for trientine, the uptake of trientine and a physiological polyamine compound, spermine, was investigated using rat renal brush-border membrane vesicles. Although, because trientine and spermine are organic cations, the H+/organic cation transporter is expected to recognize these compounds, neither an outwardly directed H+ gradient nor an inward Na+ gradient stimulated trientine uptake. [14C]Spermine uptake was, nevertheless, trans-stimulated by both unlabelled spermine and trientine and the trans-stimulating effect of spermine on trientine uptake was, furthermore, completely abolished by addition of copper ions to the incubation medium. These results suggest that there is a specific transport system for spermine and trientine on the renal brushborder membrane. This transport system contributes to the secretion of trientine in the kidney proximal tubule but does not recognize the trientine-copper complex.

  12. Metabolism and excretion of canagliflozin in mice, rats, dogs, and humans.

    Science.gov (United States)

    Mamidi, Rao N V S; Cuyckens, Filip; Chen, Jie; Scheers, Ellen; Kalamaridis, Dennis; Lin, Ronghui; Silva, Jose; Sha, Sue; Evans, David C; Kelley, Michael F; Devineni, Damayanthi; Johnson, Mark D; Lim, Heng Keang

    2014-05-01

    Canagliflozin is an oral antihyperglycemic agent used for the treatment of type 2 diabetes mellitus. It blocks the reabsorption of glucose in the proximal renal tubule by inhibiting the sodium-glucose cotransporter 2. This article describes the in vivo biotransformation and disposition of canagliflozin after a single oral dose of [(14)C]canagliflozin to intact and bile duct-cannulated (BDC) mice and rats and to intact dogs and humans. Fecal excretion was the primary route of elimination of drug-derived radioactivity in both animals and humans. In BDC mice and rats, most radioactivity was excreted in bile. The extent of radioactivity excreted in urine as a percentage of the administered [(14)C]canagliflozin dose was 1.2%-7.6% in animals and approximately 33% in humans. The primary pathways contributing to the metabolic clearance of canagliflozin were oxidation in animals and direct glucuronidation of canagliflozin in humans. Unchanged canagliflozin was the major component in systemic circulation in all species. In human plasma, two pharmacologically inactive O-glucuronide conjugates of canagliflozin, M5 and M7, represented 19% and 14% of total drug-related exposure and were considered major human metabolites. Plasma concentrations of M5 and M7 in mice and rats from repeated dose safety studies were lower than those in humans given canagliflozin at the maximum recommended dose of 300 mg. However, biliary metabolite profiling in rodents indicated that mouse and rat livers had significant exposure to M5 and M7. Pharmacologic inactivity and high water solubility of M5 and M7 support glucuronidation of canagliflozin as a safe detoxification pathway.

  13. Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.

    Science.gov (United States)

    Kimura, Sahika; Ueda, Yuka; Ise, Takayuki; Yagi, Shusuke; Iwase, Takashi; Nishikawa, Koji; Yamaguchi, Koji; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Katoh, Shinsuke; Akaike, Masashi; Yasui, Natsuo; Sata, Masataka

    2015-01-01

    Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.

  14. 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

  15. Diuretic use in renal disease.

    Science.gov (United States)

    Sica, Domenic A

    2011-12-20

    Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type diuretics, loop diuretics and K(+)-sparing diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na(+) and K(+) axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.

  16. The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids.

    Science.gov (United States)

    Lotito, Silvina B; Frei, Balz

    2004-07-15

    Regular fruit consumption lowers the risk of cardiovascular diseases and certain cancers, which has been attributed in part to fruit-derived antioxidant flavonoids. However, flavonoids are poorly absorbed by humans, and the increase in plasma antioxidant capacity observed after consumption of flavonoid-rich foods often greatly exceeds the increase in plasma flavonoids. In the present study, six healthy subjects consumed five Red Delicious apples (1037 +/- 38 g), plain bagels (263.1 +/- 0.9 g) and water matching the carbohydrate content and mass of the apples, and fructose (63.9 +/- 2.9 g) in water matching the fructose content and mass of the apples. The antioxidant capacity of plasma was measured before and up to 6 h after food consumption as ferric reducing antioxidant potential (FRAP), without or with ascorbate oxidase treatment (FRAPAO) to estimate the contribution of ascorbate. Baseline plasma FRAP and FRAPAO were 445 +/- 35 and 363 +/- 35 microM trolox equivalents, respectively. Apple consumption caused an acute, transient increase in both plasma FRAP and FRAPAO, with increases after 1 h of 54.6 +/- 8.7 and 61.3 = 17.2 microM trolox equivalents, respectively. This increase in plasma antioxidant capacity was paralleled by a large increase in plasma urate, a metabolic antioxidant, from 271 +/- 39 microM at baseline to 367 +/- 43 microM after 1 h. In contrast, FRAP and FRAPAO time-dependently decreased after bagel consumption, together with urate. Consumption of fructose mimicked the effects of apples with respect to increased FRAP, FRAPAO, and urate, but not ascorbate. Taken together, our data show that the increase in plasma antioxidant capacity in humans after apple consumption is due mainly to the well-known metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids.

  17. 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.

  18. Simultaneous management for retrocaval ureter and ipsilateral renal stone using retroperitoneoscopic approach: report of a case

    OpenAIRE

    Suzuki, Shouji; Sawada, Norifumi; Haheda,Yaburu; Zakoji, Hidenori; Tsuchida, Takayuki; Aikawa,Masami; Adaki ,Isao; Takeda, Masayuki

    2009-01-01

    A 32-year-old male presented with a month history of right back and flank pain and a possibility of gross hematuria. As part of the initial evaluation abdominal ultrasound revealed marked right hydronephrosis. An excretion urogram showed delayed excretion of contrast material extending to the L4 level distally. Computed omography revealed right renal pelvic stone and right retrocaval ureter. At surgery, a right-sided ouble-J ureteric stent was placed under fluoroscopic guidance. Retroperitone...

  19. Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats.

    Science.gov (United States)

    Gohar, Eman Y; Speed, Joshua S; Kasztan, Malgorzata; Jin, Chunhua; Pollock, David M

    2016-08-01

    Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na(+) reabsorption in the renal medulla. A link between the renal ET-1 and purinergic systems was demonstrated in vitro, however, the in vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na(+) excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague-Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic saline (NaCl; 284 mosmol/kgH2O) was infused into the medullary interstitium (500 μl/h) during a 30-min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) for two further 30-min urine collection periods. Na(+) excretion was significantly increased during intramedullary infusion of hyperosmotic saline. Compared with isosmotic saline, hyperosmotic saline infused into the renal medulla caused significant increases in inner medullary ET-1 mRNA expression. Renal intramedullary infusion of the P2 receptor antagonist suramin inhibited the increase in Na(+) excretion and inner medullary ET-1 mRNA expression induced by NaCl loading in the renal medulla. Activation of medullary P2Y2/4 receptors by infusion of UTP increased urinary Na(+) excretion. Combined ETA and ETB receptor blockade abolished the natriuretic response to intramedullary infusion of UTP. These data demonstrate that activation of medullary P2 receptors promotes ET-dependent natriuresis in male rats, suggesting that the renal ET-1 and purinergic signaling systems interact to efficiently facilitate excretion of a NaCl load.

  20. Urinary Excretion of Phenolic Acids by Infants and Children: A Randomised Double-Blind Clinical Assay

    Science.gov (United States)

    Uberos, J.; Fernández-Puentes, V.; Molina-Oya, M.; Rodríguez-Belmonte, R.; Ruíz-López, A.; Tortosa-Pinto, P.; Molina-Carballo, A.; Muñoz-Hoyos, A.

    2012-01-01

    Objectives: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. Methods: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. Results: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024–1.1; P = 0.001). Conclusions: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options. PMID:23641168

  1. 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.

  2. Dietary intake and urinary excretion of lignans in Finnish men

    DEFF Research Database (Denmark)

    Nurmi, Tarja; Mursu, Jaakko; Peñalvo, José L;

    2010-01-01

    Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100....../d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion...

  3. Dietary intake and urinary excretion of lignans in Finnish men

    DEFF Research Database (Denmark)

    Nurmi, Tarja; Mursu, Jaakko; Peñalvo, José L;

    2010-01-01

    of plant lignans was explained 14 % by the intake of rye products and intake of coffee, and consequently 3-7 % by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11 % by the intake of vegetables and rye products, 14 % by the intake of water-soluble fibre and only 4....../d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion...

  4. Altered urinary excretion of aquaporin 2 in IgA nephropathy.

    Science.gov (United States)

    Rocchetti, Maria Teresa; Tamma, Grazia; Lasorsa, Domenica; Suriano, Ida Valentina; D'Apollo, Annamaria; Papale, Massimo; Mastrofrancesco, Lisa; Grandaliano, Giuseppe; Svelto, Maria; Valenti, Giovanna; Gesualdo, Loreto; Di Paolo, Salvatore

    2011-10-01

    The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indirectly, via RAS activation. Our aim is to explore the intrarenal activity of AVP, its relationship with RAS activity, as well as its modulation by therapies in IgAN. In this observational study, we measured plasma copeptin, a surrogate marker of AVP, the urine excretion of aquaporin 2 (AQP2), a protein reflecting renal AVP action, and angiotensinogen (AGT), a parameter of renal RAS activation, and their relationship with renal function in 44 IgAN patients at the time of renal biopsy, without any drug therapy, and after 6-month treatment with ACEi or steroid+ACEi. Twenty-one patients with other CKD and 40 healthy subjects were recruited as controls. ELISAs were used to measure all variables of interest. At baseline, IgAN patients showed higher urinary levels of AQP2, compared with controls and patients with other CKD. Urinary AQP2 and AGT levels strongly correlated with the presence of arterial hypertension. Steroids+ACEi caused the decrease of all the variables examined. The fall of urinary AQP2 and AGT following drug treatments was associated with the decrease of daily proteinuria. Our findings would support the involvement of AVP-AQP2 axis, interacting with the RAS, in the progression of IgAN and candidate AQP2 as a possible novel marker of the disease.

  5. Progression of urinary protein excretion after kidney transplantation: A marker for poor long-term prognosis.

    Science.gov (United States)

    Borrego Hinojosa, Josefa; Gentil Govantes, Miguel Angel; Cabello Díaz, Mercedes; Rodriguez Benot, Alberto; Mazuecos Blanca, Auxiliadora; Osuna Ortega, Antonio; Bedoya Pérez, Rafael; Castro De La Nuez, Pablo; Alonso Gil, Manuel

    2015-01-01

    Post-transplantation proteinuria is a risk factor for graft failure. A progressive decline in renal graft function is a predictor for mortality in kidney transplant patients. To assess the development and the progression of urinary protein excretion (UPE) in the first year post-transplant in recipients of kidney transplants and its effect on patient and graft outcomes. We analysed 1815 patients with 24-h UPE measurements available at 3 and 12 months post-transplant. Patients were divided based on their UPE level: below 300 mg, 300-1000 mg and over 1000 mg (at 3 and 12 months), and changes over time were analysed. At 3 months, 65.7% had UPE below 300 mg/24 h, 29.6% 300-1000 mg/24 h and 4.7% over 1000 mg/24h. At one year, 71.6% had UPE below 300 mg/24 h, 24.1% 300-1000 mg/24 h and 4.4% over 1000 mg/24 h. In 208 patients (12%), the UPE progressed, in 1233 (70.5%) it remained stable and in 306 (17.5%) an improvement was observed. We found that the level of UPE influenced graft survival, particularly if a progression occurred. Recipient's age and renal function at one year were found to be predictive factors for mortality, while proteinuria and renal function were predictive factors for graft survival. Proteinuria after transplantation, essentially when it progresses, is a marker of a poor prognosis and a predictor for graft survival. Progression of proteinuria is associated with poorer renal function and lower graft survival rates. Copyright © 2015. Published by Elsevier España, S.L.U.

  6. Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

    DEFF Research Database (Denmark)

    Osther, P J; Bollerslev, Jens; Hansen, A B

    1993-01-01

    Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had......-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA....

  7. Accelerated urinary excretion of methylmercury following administration of its antidote N-acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance-associated protein.

    Science.gov (United States)

    Madejczyk, Michael S; Aremu, David A; Simmons-Willis, Tracey A; Clarkson, Thomas W; Ballatori, Nazzareno

    2007-07-01

    N-Acetylcysteine (NAC) is a sulfhydryl-containing compound that produces a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned mice, but the molecular mechanism for this effect is poorly defined. MeHg readily binds to NAC to form the MeHg-NAC complex, and recent studies indicate that this complex is an excellent substrate for the basolateral organic anion transporter (Oat)-1, Oat1/Slc22a6, thus potentially explaining the uptake from blood into the renal tubular cells. The present study tested the hypothesis that intracellular MeHg is subsequently transported across the apical membrane of the cells into the tubular fluid as a MeHg-NAC complex using the multidrug resistance-associated protein-2 (Mrp2/Abcc2). NAC markedly stimulated urinary [(14)C]MeHg excretion in wild-type Wistar rats, and a second dose of NAC was as effective as the first dose in stimulating MeHg excretion. In contrast with the normal Wistar rats, NAC was much less effective at stimulating urinary MeHg excretion in the Mrp2-deficient (TR-) Wistar rats. The TR- rats excreted only approximately 30% of the MeHg excreted by the wild-type animals. To directly test whether MeHg-NAC is a substrate for Mrp2, studies were carried out in plasma membrane vesicles isolated from livers of TR- and control Wistar rats. Transport of MeHg-NAC was lower in vesicles prepared from TR- rats, whereas transport of MeHg-cysteine was similar in control and TR- rats. These results indicate that Mrp2 is involved in urinary MeHg excretion after NAC administration and suggest that the transported molecule is most likely the MeHg-NAC complex.

  8. Selective renal vasodilation and active renal artery perfusion improve renal function in dogs with acute heart failure.

    Science.gov (United States)

    Suehiro, K; Shimizu, J; Yi, G H; Gu, A; Wang, J; Keren, G; Burkhoff, D

    2001-09-01

    Renal failure is common in heart failure due to renovascular constriction and hypotension. We tested whether selective pharmacological renal artery vasodilation and active renal artery perfusion (ARP) could improve renal function without adverse effects on systemic blood pressure in a canine model of acute heart failure (AHF). AHF was induced by coronary microembolization in 16 adult mongrel dogs. In five dogs, selective intrarenal (IR) papaverine (1, 2, and 4 mg/min) was administered into the left renal artery. In six dogs, ARP was performed in the left renal artery to normalize mean renal arterial pressure followed by administration of IR papaverine (2 mg/min). In five dogs, ARP plus intravenous furosemide was tested. Urine output (UO) and cortical renal blood flow decreased during AHF and were restored by 2 mg/min IR papaverine (UO: baseline 4.2 +/- 0.6, AHF 1.6 +/- 1.3, IR papaverine 5.8 +/- 1.1 ml/15 min; cortical blood flow: baseline 4.3 +/- 0.2, AHF 2.4 +/- 0.6, IR papaverine 4.2 +/- 1.2 ml/min/g) with no significant change in aortic pressure. ARP also increased urine output and cortical renal blood flow (UO: baseline 5.0 +/- 1.1, AHF 0.5 +/- 0.4, ARP 3.8 +/- 3.1 ml/15 min; cortical blood flow: baseline 4.0 +/- 0.5, AHF 2.0 +/- 0.8, ARP 3.52 +/- 1.1 ml/min/g). A combination of these methods in AHF further increased urine output to twice the normal baseline (10.5 +/- 7.5 ml/15 min). Addition of furosemide synergistically increased UO above that achieved with ARP alone (5.5 +/- 2.6 versus 40.3 +/- 24.7 ml/15 min, p = 0.03). In conclusion, ARP and selective renal vasodilation may effectively promote salt and water excretion in the setting of heart failure, particularly when systemic blood pressure is low.

  9. Renal concentration defect following nonoliguric acute renal failure in the rat.

    Science.gov (United States)

    Anderson, R J; Gordon, J A; Kim, J; Peterson, L M; Gross, P A

    1982-04-01

    The mechanism of impaired renal concentrating ability following nonoliguric ischemic acute renal failure was studied in the rat. Fifty min of complete occlusion of the renal artery and vein with contralateral nephrectomy resulted in reversible, nonoliguric acute renal failure. Eight days following induction of acute renal failure, a defect in 30 hr dehydration urine osmolality was present when experimental animals were compared with uninephrectomized controls (1,425 +/- 166 versus 2,267 +/- 127 mOsm/kg water respectively, P less than 0.001). Comparable postdehydration plasma vasopressin levels in experimental and control animals and an impaired hydro-osmotic response to exogenous vasopressin in experimental animals documented a nephrogenic origin of the defect in urine concentration. Lower urinary excretion of prostaglandin E2 in experimental animals and a failure of cyclo-oxygenase inhibition with 10 mg/kg of indomethacin to improve dehydration urine osmolality suggested that prostaglandin E2 antagonism of vasopressin action did not contribute to the concentration defect. Postdehydration inner medullary (papillary) interstitial tonicity was significantly reduced in experimental animals versus controls (870 +/- 85 versus 1,499 +/- 87 mOsm/kg water respectively, P less than 0.001). To determine if this decreased interstitial tonicity was due to vascular mechanisms, papillary plasma flow was measured and found to be equivalent in experimental and control animals. To examine a role for biochemical factors in the renal concentration defect, cyclic nucleotide levels were measured in cytosol and membrane fragments. A decrease in vasopressin and sodium fluoride-stimulated adenylate cyclase was found in outer medullary tissue of experimental animals. In contrast, vasopressin-stimulated adenylate cyclase activity was comparable in the inner medullary tissue of control and experimental animals. Our study suggests a defect in generation of renal inner medullary interstitial

  10. 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...

  11. Carbonated beverages and urinary calcium excretion.

    Science.gov (United States)

    Heaney, R P; Rafferty, K

    2001-09-01

    Intake of carbonated beverages has been associated with increased fracture risk in observational studies. The usual explanation given is that one or more of the beverage constituents increase urinary calcium. We assessed the short-term effects on urinary calcium excretion of carbonated beverages of various compositions. An incomplete random block design was used to study 20-40-y-old women who customarily consumed > or =680 mL carbonated beverages daily. Four carbonated beverages were tested: 2 with caffeine and 2 without. Two contained phosphoric acid as the acidulant and 2 contained citric acid. The study included one neutral control (water) and one positive control (skim or chocolate milk). Serving size was 567 mL for the carbonated beverages and water and 340 mL for the milks. Beverages were consumed with a light breakfast after an overnight fast; no other foods were ingested until urine collection was complete. pH, titratable and total acidity, sodium, creatinine, and calcium were measured in 2-h (morning) fasting and 5-h postbeverage urine specimens. Relative to water, urinary calcium rose significantly only with the milks and the 2 caffeine-containing beverages. The excess calciuria was approximately 0.25 mmol, about the same as previously reported for caffeine alone. Phosphoric acid without caffeine produced no excess calciuria; nor did it augment the calciuria of caffeine. The excess calciuria associated with consumption of carbonated beverages is confined to caffeinated beverages. Acidulant type has no acute effect. Because the caffeine effect is known to be compensated for by reduced calciuria later in the day, we conclude that the net effect of carbonated beverage constituents on calcium economy is negligible. The skeletal effects of carbonated beverage consumption are likely due primarily to milk displacement.

  12. Excretion of Δ9-Tetrahydrocannabinol in Sweat

    Science.gov (United States)

    Huestis, Marilyn A.; Scheidweiler, Karl B.; Saito, Takeshi; Fortner, Neil; Abraham, Tsadik; Gustafson, Richard A.; Smith, Michael L.

    2008-01-01

    Sweat testing is a noninvasive technique for monitoring drug exposure over a 7-day period in treatment, criminal justice, and employment settings. We evaluated Δ9-tetrahydrocannabinol (THC) excretion in 11 daily cannabis users after cessation of drug use. PharmChek® sweat patches worn for 7 days were analyzed for THC by gas chromatography-mass spectrometry (GC/MS). The limit of quantification (LOQ) for the method was 0.4 ng THC/patch. Sweat patches worn the first week of continuously monitored abstinence had THC above the United States Substance Abuse Mental Health Services Administration’s proposed cutoff concentration for federal workplace testing of 1 ng THC/patch. Mean ± S.E.M. THC concentrations were 3.85 ± 0.86 ng THC/patch. Eight of 11 subjects had negative patches the second week and one produced THC positive patches for four weeks of monitored abstinence. We also tested daily and weekly sweat patches from 7 subjects who were administered oral doses of up to 14.8 mg THC/day for five consecutive days. In this oral THC administration study, no daily or weekly patches had THC above the LOQ; concurrent plasma THC concentrations were all less than 6.1 μg/L. In conclusion, using proposed federal cutoff concentrations, most daily cannabis users will have a positive sweat patch in the first week after ceasing drug use and a negative patch after subsequent weeks, although patches may remain positive for four weeks or more. Oral ingestion of up to 14.8 mg THC daily does not produce a THC positive sweat patch test. PMID:17481836

  13. Renal Localization of {sup 67}Ga Citrate in Noninfectious Nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu [Chungnam University College of Medicine, Deajeon (Korea, Republic of)

    1992-07-15

    {sup 67}Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of {sup 67}Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal {sup 67}Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of {sup 67}Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher {sup 67}Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal {sup 67}Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal {sup 67}Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, {sup 67}Ga citrate scan is useful in predicting renal involvement.

  14. 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-match...

  15. Brief periods of hyperphagia cause renal injury in the obese Zucker rat

    NARCIS (Netherlands)

    Gades, MD; van Goor, H; Kaysen, GA; Johnson, PR; Horwitz, BA; Stern, JS

    1999-01-01

    Background. Female obese (fa/fa) Zucker rats are maximally hyperphagic from the beginning of access to solid food until 20 weeks of age and die primarily from renal failure. We documented that urinary albumin excretion (UAE) rises early in obese rats during this time of greatest hyperphagia. This st

  16. Biotransformation, transport and toxicity studies in rat renal proximal tubular cells.

    NARCIS (Netherlands)

    Haenen, H.E.M.G.

    1996-01-01

    SummaryRenal proximal tubular (RPT) cells can be exposed apically to glomerulary filtrated and basolaterally to non-filtrated nephrotoxic compounds. To excrete these compounds via the urine, RPT cells are equipped with transport systems able to transport nephrotoxicants from the basolateral to the a

  17. Defective renal dopamine D1 receptor function contributes to hyperinsulinemia-mediated hypertension.

    Science.gov (United States)

    Ahmad Banday, Anees; Lokhandwala, Mustafa F

    2006-11-01

    Hyperinsulinemia is reported to play a role in hypertension, as abnormalities in blood pressure regulation and sodium handling exist in diabetes mellitus. Kidney dopamine promotes sodium excretion via the activation of renal D1 receptors. Because there is a close relationship between renal D1 receptor function and sodium excretion, it is hypothesized that a defect in this mechanism may contribute to decreased sodium excretion and hypertension during hyperinsulinemia. Renal D1 receptor function was studied in insulin-induced hypertension in male Sprague Dawley rats. Insulin pellets were implanted subcutaneously for controlled insulin release for three weeks; sham rats served as a control. Compared to control rats, insulin pellets increased plasma insulin levels by eight fold and decreased blood glucose by 40%. Insulin also caused a 22 mmHg increase in mean arterial blood pressure compared to control animals. The intravenous infusion of SKF-38393, a D1 receptor agonist, increased sodium excretion in control rats, but SKF-38393 failed to produce natriuresis in hyperinsulinemic animals. Renal proximal tubules from hyperinsulinemic rats had a reduced D1 receptor number, defective receptor-G protein coupling, and blunted SKF-38393 induced Na, K-ATPase inhibition. Insulin seems to reduce D1 receptor expression and coupling to the G-protein, leading to a reduced D1 receptor-mediated Na, K-ATPase inhibition, and a diminished natriuretic response to SKF-38393. These phenomena could account for sodium retention and hypertension associated with hyperinsulinemia.

  18. THE EFFECTS OF ALPHA-ADRENOCEPTOR BLOCKADE ON DOPAMINE-INDUCED RENAL VASODILATION AND NATRIURESIS

    NARCIS (Netherlands)

    SMIT, AJ; MEIJER, S; WESSELING, H; DONKER, AJM; REITSMA, WD

    1991-01-01

    To establish the effects of alpha-adrenoceptor blockade on dopamine-induced changes in renal hemodynamics and sodium excretion, dopamine dose-response curves were performed without and with pre-treatment with the selective postsynaptic alpha-1-adrenoceptor antagonist prazosin in normal volunteers an

  19. Role of the distal convoluted tubule in renal Mg(2+) handling: molecular lessons from inherited hypomagnesemia

    NARCIS (Netherlands)

    Ferre, S.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2011-01-01

    In healthy individuals, Mg(2+) homeostasis is tightly regulated by the concerted action of intestinal absorption, exchange with bone, and renal excretion. The kidney, more precisely the distal convoluted tubule (DCT), is the final determinant of plasma Mg(2+) concentrations. Positional cloning strat

  20. Brief periods of hyperphagia cause renal injury in the obese Zucker rat

    NARCIS (Netherlands)

    Gades, MD; van Goor, H; Kaysen, GA; Johnson, PR; Horwitz, BA; Stern, JS

    1999-01-01

    Background. Female obese (fa/fa) Zucker rats are maximally hyperphagic from the beginning of access to solid food until 20 weeks of age and die primarily from renal failure. We documented that urinary albumin excretion (UAE) rises early in obese rats during this time of greatest hyperphagia. This st

  1. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption.

    NARCIS (Netherlands)

    Voets, T.; Nilius, B.; Hoefs, S.J.G.; Kemp, J.W.C.M. van der; Droogmans, G.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2004-01-01

    Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes and a major constituent of bone tissue. Mg2+ homeostasis in mammals depends on the equilibrium between intestinal Mg2+ absorption and renal Mg2+ excretion, but little is known about the molecular nature of

  2. Sodium intake affects urinary albumin excretion especially in overweight subjects

    NARCIS (Netherlands)

    Verhave, J C; Hillege, H L; Burgerhof, J G M; Janssen, W M T; Gansevoort, R T; Navis, G J; de Zeeuw, D; de Jong, P E; Postma, Maarten

    2004-01-01

    Objectives. To examine the relationship between sodium intake and urinary albumin excretion, being an established risk marker for later cardiovascular morbidity and mortality. Design. Cross-sectional cohort study using linear regression analysis. Setting: University hospital outpatient clinic. Subje

  3. Sodium intake affects urinary albumin excretion especially in overweight subjects

    NARCIS (Netherlands)

    Verhave, J C; Hillege, H L; Burgerhof, J G M; Janssen, W M T; Gansevoort, R T; Navis, G J; de Zeeuw, D; de Jong, P E; Postma, Maarten

    2004-01-01

    Objectives. To examine the relationship between sodium intake and urinary albumin excretion, being an established risk marker for later cardiovascular morbidity and mortality. Design. Cross-sectional cohort study using linear regression analysis. Setting: University hospital outpatient clinic. Subje

  4. Ammonia excretion in mytilid mussels is facilitated by ciliary beating.

    Science.gov (United States)

    Thomsen, J; Himmerkus, N; Holland, N; Sartoris, F J; Bleich, M; Tresguerres, M

    2016-08-01

    The excretion of nitrogenous waste products in the form of ammonia (NH3) and ammonium (NH4 (+)) is a fundamental process in aquatic organisms. For mytilid bivalves, little is known about the mechanisms and sites of excretion. This study investigated the localization and the mechanisms of ammonia excretion in mytilid mussels. An Rh protein was found to be abundantly expressed in the apical cell membrane of the plicate organ, which was previously described as a solely respiratory organ. The Rh protein was also expressed in the gill, although at significantly lower concentrations, but was not detectable in mussel kidney. Furthermore, NH3/NH4 (+) was not enriched in the urine, suggesting that kidneys are not involved in active NH3/NH4 (+) excretion. Exposure to elevated seawater pH of 8.5 transiently reduced NH3/NH4 (+) excretion rates, but they returned to control values following 24 h acclimation. These mussels had increased abundance of V-type H(+)-ATPase in the apical membranes of plicate organ cells; however, NH3/NH4 (+) excretion rates were not affected by the V-type H(+)-ATPase specific inhibitor concanamycin A (100 nmol l(-1)). In contrast, inhibition of ciliary beating with dopamine and increased seawater viscosity significantly reduced NH3 excretion rates under control pH (8.0). These results suggest that NH3/NH4 (+) excretion in mytilid mussels takes place by passive NH3 diffusion across respiratory epithelia via the Rh protein, facilitated by the water current produced for filter feeding, which prevents accumulation of NH3 in the boundary layer. This mechanism would be energy efficient for sessile organisms, as they already generate water currents for filter feeding. © 2016. Published by The Company of Biologists Ltd.

  5. [Fluoride urinary excretion in Mexico City's preschool children].

    Science.gov (United States)

    Juárez-López, María Lilia Adriana; Hernández-Guerrero, Juan Carlos; Jiménez-Farfán, Dolores; Molina-Frechero, Nelly; Murrieta-Pruneda, Francisco; López-Jiménez, Georgina

    2008-01-01

    The assessment of urinary fluoride excretion during dental developing stage has been reported for different countries with community fluoride programs. Also, one of the factors that could influence on retention and excretion of fluoride is the deficient nutrition so the aim of this study was to determine fluoride urinary excretion by a group of preschool children with and without malnutrition. Urinary samples from 24 hours were collected from 60 preschool children selected by convenience from Iztapalapa area of Mexico City, 30 with malnutrition and 30 with standard nutritrional status by weight for age. The samples were analyzed by fluoride especific electrode. Orion 720A. The average concentration of fluoride in urine from preschool children with and without malnutrition were 0.89 +/- 0.4 mg/L and 0.80 +/- 0.3 mg/L, respectively. The mean of 24 hours total fluoride excreted were 367 +/- 150 microg/24 hrs. in malnutrition children and 355 +/- 169 microg/24 hrs. for those with standard nutritional status. There were no differences statistically significant between groups. The urinary fluoride excretion for children with and without malnutrition were in the optimal range of fluoridation for the prevention of caries decay. Malnutrition was no associated with changes on fluoride orine concentration and excretion rates.

  6. 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.

  7. Effects of RuPeng15 Powder (RPP15 on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

    Directory of Open Access Journals (Sweden)

    Y.-Y. Kou

    2015-01-01

    Full Text Available RuPeng15 Powder (RPP15 is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65 in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, and interleukin-8 (IL-8 in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg. We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues.

  8. Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

    Directory of Open Access Journals (Sweden)

    Jung-Yoon Choe

    2015-01-01

    Full Text Available The aim of this study was to clarify the role of monosodium urate (MSU crystals in receptor activator of nuclear factor kB ligand- (RANKL- RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9, in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6, JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout.

  9. Diff-Quik® staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids

    Directory of Open Access Journals (Sweden)

    M. Hammoud

    2011-09-01

    Full Text Available The aim of this study was to evaluate whether DQ could prove useful to identify monosodium urate (MSU and calcium pyrophosphate dehydrate (CPPD crystals on permanent mounted stained slides. To this end, we studied 27 synovial fluid (SF samples obtained from the knees of patients with the pseudogout (n=21 and acute gouty arthritis (n=6. Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, we studied 16 inflammatory synovial effusions obtained from patients with knee arthritis not induced by crystals. For each SF, DQ stained slides were analyzed by 2 experienced doctors in SF analysis. The observers were blinded to the type of crystal present in the SF. Each slide was analyzed by compensated polarized and transmitted light microscopy. SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observers were asked to identify the type of the crystals using compensated polarized light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV, and negative predictive value (NPV of the DQ staining method were determined. 51 true positive and 28 true negative specimens were correctly classified (39 CPPD samples, 12 MSU samples, and 28 samples of crystals-unrelated arthropathies. All MSU specimens were correctly diagnosed.

  10. Effects of Extract from Mangifera indica Leaf on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2012-01-01

    Full Text Available The leaves of Mangifera indica L. (Anacardiaceae is used as a medicinal material in traditional herb medicine for a long time in India, China, and other Eastern Asian countries. Our present study investigated the therapeutic effects of the ethanol extract from Mangifera indica (EMI in rat with monosodium urate (MSU crystals-induced gouty arthritis. Effects of EMI (50, 100, and 200 mg/kg, p.o. administrated for 9 days on the ankle swelling, synovial tumor necrosis factor-alpha (TNF-α, and interleukin-1beta (IL-1β levels were assessed in MSU crystal rat. Data from our study showed that rat with gouty arthritis induced by MSU crystal demonstrated an elevation in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. Oral administration of 100 and 200 mg/kg EMI for 9 days reversed the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. The results indicated that the beneficial antigouty arthritis effect of EMI may be mediated, at least in part, by inhibiting TNF-α and IL-1β expression in the synovial tissues. Our study suggests that Mangifera indica and its extract may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.

  11. The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints.

    Science.gov (United States)

    Galozzi, Paola; Oliviero, Francesca; Frallonardo, Paola; Favero, Marta; Hoxha, Ariela; Scanu, Anna; Lorenzin, Mariagrazia; Ortolan, Augusta; Punzi, Leonardo; Ramonda, Roberta

    2016-03-01

    The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

  12. 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.

  13. 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

  14. 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...

  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. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone, a phosphodies......In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......). LPS-induced fall in GFR and proximal tubular outflow were sustained on day 2. Furthermore, LPS-treated rats showed a marked increase in fractional distal water excretion, despite significantly elevated levels of plasma vasopressin (AVP). Semiquantitative immunoblotting showed that LPS increased......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape...

  17. Approach to renal clycosuria in children: a case report

    Directory of Open Access Journals (Sweden)

    Patrícia Pais

    2016-02-01

    Full Text Available Introduction: The accidental finding of glycosuria should lead to the exclusion of diabetes mellitus. In the absence of hyperglycemia, glycosuria is probably of renal origin. It can be isolated, as in familiar renal glycosuria, or it can be part of a hereditary tubular disorder such as Fanconi-Bickel syndrome or associated with an acquired tubular dysfunction. The renal and tubular function should be investigated. Case report: The authors describe the case of a previously healthy five-year old child with persistent glycosuria of renal cause. The investigation showed the coexistence of elevated renal excretion of glycine. Discussion: Familiar renal glycosuria and hyperglycinuria are caused by genetic defects in different renal tubular membrane transporters. The rare association of glycosuria and glycinuria was only described in one family in the 1960’s. The authors discuss the possible pathophysiologic mechanisms of this association and the importance of studying other tubulopathies in a child with glycosuria as it has prognostic and clinical management implications.

  18. Cigarette smoking: an important renal risk factor – far beyond carcinogenesis

    Directory of Open Access Journals (Sweden)

    Orth SR

    2002-06-01

    Full Text Available Abstract In recent years, it has become apparent that smoking has a negative impact on renal function, being one of the most important remediable renal risk factors. It has been clearly shown that the risk for high-normal urinary albumin excretion and microalbuminuria is increased in smoking compared to non-smoking subjects of the general population. Data from the Multiple Risk Factor Intervention Trial (MRFIT indicate that at least in males, smoking increases the risk to reach end-stage renal failure. Smoking is particularly "nephrotoxic" in older subjects, subjects with essential hypertension and patients with preexisting renal disease. Of interest, the magnitude of the adverse renal effect of smoking seems to be independent of the underlying renal disease. Death-censored renal graft survival is decreased in smokers, indicating that smoking also damages the renal transplant. Cessation of smoking has been show to reduce the rate of progression of renal failure both in patients with renal disease or a renal transplant. The mechanisms of smoking-induced renal damage are only partly understood and comprise acute hemodynamic (e.g., increase in blood pressure and presumably intraglomerular pressure and chronic effects (e.g., endothelial cell dysfunction. Renal failure per se leads to an increased cardiovascular risk. The latter is further aggravated by smoking. Particularly survival of smokers with diabetes mellitus on hemodialysis is abysmal. In the present review article the current state of knowledge about the renal risks of smoking is reviewed. It is the aim of the article to point out that smoking not only increases the risk of renal cell carcinoma or uroepithelial cell carcinoma, but also the risk of a faster decline of renal function. The latter is a relatively new negative aspect which has not been widely recognized.

  19. Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

    Science.gov (United States)

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

  20. Pharmacological and clinical studies with temocapril, an angiotensin converting enzyme inhibitor that is excreted in the bile.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Yoshikawa, Junichi; Asada, Akira

    2004-01-01

    Temocapril is an angiotensin converting enzyme inhibitor (ACEI), a prodrug with a thiazepine ring. Its active form, temocaprilat, is slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of temocaprilat on isolated rat aorta is 3 times that of enalaprilat. Temocapril is excreted in the bile and urine and can be used in patients with renal insufficiency. It reduces blood pressure without causing any significant change in heart rate or cardiac output. Temocapril has been reported to improve endothelial dysfunction in vitro by suppressing increased oxidative stress. In vivo it improves reactive hyperemia in patients with essential hypertension. It has been reported to prevent coronary vascular remodeling in vivo by suppressing local ACE and increased oxidative stress. In humans temocapril has been found to improve insulin resistance partly by increasing adiponectin levels. Cardiac remodeling was improved by temocapril not only in experiment animals but also in humans. It improves renal function and decreases urinary albumin excretion in diabetics as well as in hypertensive patients. Temocapril is currently marketed only in Japan. Considering its beneficial effects and unique pharmacokinetics, temocapril, is likely to be introduced in other countries as well.

  1. Urinary oxalate excretion by very low birth weight infants receiving parenteral nutrition.

    Science.gov (United States)

    Campfield, T; Braden, G

    1989-11-01

    Renal calcifications have been described in very low birth weight (VLBW) infants, and diuretic drug-associated hypercalciuria is believed to play a role in the pathogenesis of this lesion. Hyperoxaluria is an important cause of renal stone formation in children and adults. Because parenteral nutrition solutions contain the oxalate precursors ascorbate and glycine, the relationship between total parenteral nutrition administration and oxalate excretion in VLBW infants was examined. Administration of approximately 0.5 g of total parenteral nutrition protein per kilogram per day to VLBW infants was associated with an increased urinary oxalate concentration and an increased urinary oxalate to creatinine ratio, when compared with VLBW infants receiving a glucose and electrolyte solution. A further increase in urinary oxalate concentration and oxalate to creatinine ratio was noted when total parenteral nutrition protein was increased to approximately 1.5 g of protein per kilogram per day. In VLBW infants who receive total parenteral nutrition, elevated urinary oxalate concentrations may develop and may be a factor in the pathogenesis of nephrocalcinosis in these infants.

  2. Urinary CYP eicosanoid excretion correlates with glomerular filtration in African-Americans with chronic kidney disease.

    Science.gov (United States)

    Dreisbach, Albert W; Smith, Stanley V; Kyle, Patrick B; Ramaiah, Manjunath; Amenuke, Margaret; Garrett, Michael R; Lirette, Seth T; Griswold, Michael E; Roman, Richard J

    2014-10-01

    Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005]ml/min/for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD.

  3. Urinary CYP Eicosanoid Excretion Correlates with Glomerular Filtration in African-Americans with Chronic Kidney Disease

    Science.gov (United States)

    Dreisbach, Albert W; Smith, Stanley V; Kyle, Patrick B; Ramaiah, Manjunath; Amenuke, Margaret; Garrett, Michael R; Lirette, Seth T; Griswold, Michael E; Roman, Richard J

    2015-01-01

    Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/ creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005] ml/min/ for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD. PMID:25151892

  4. Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.

    Directory of Open Access Journals (Sweden)

    Cristina Zanchi

    Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.

  5. The effect of high-dose nifedipine on renal hemodynamics of cyclosporine-treated renal allograft recipients.

    Science.gov (United States)

    Chagnac, A; Zevin, D; Ori, Y; Korzets, A; Hirsh, J; Levi, J

    1992-04-01

    Cyclosporine has been shown to reduce renal perfusion and to decrease glomerular filtration rate. Experimental studies suggest that nifedipine might reverse this renal vasoconstrictive effect of cyclosporine. We studied renal hemodynamics of 5 cyclosporine-treated renal transplant recipients before and after 2 weeks of therapy with high-dose nifedipine (up to 120 mg/day). Pretreatment GFR and renal plasma flow (RPF) were decreased. Following administration of nifedipine, RPF increased by 18% (P less than 0.01), while GFR did not change. Filtration fraction decreased by 10.5% (P less than 0.01). Mean arterial pressure declined from 111 +/- 5 to 96 +/- 3 mmHg (P less than 0.01). Renal vascular resistance dropped by 25% (P less than 0.01). Calculated postglomerular plasma flow increased by 20.5% (P less than 0.01). Urinary albumin excretion rate was unaffected. Cyclosporine whole blood levels were unchanged. The increase in RPF and in postglomerular plasma flow suggests that high-dose nifedipine might lessen cyclosporine-induced glomerular and interstitial ischemia in renal allograft recipients.

  6. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

  7. Drug administration in patients with renal insufficiency. Minimising renal and extrarenal toxicity.

    Science.gov (United States)

    Matzke, G R; Frye, R F

    1997-03-01

    Renal insufficiency has been associated with an increased risk of adverse effects with many classes of medications. The risk of some, but not all, adverse effects has been linked to the patient's degree of residual renal function. This may be the result of inappropriate individualisation of those agents that are primarily eliminated by the kidney, or an alteration in the pharmacodynamic response as a result of renal insufficiency. The pathophysiological mechanism responsible for alterations in drug disposition, especially metabolism and renal excretion, is the accumulation of uraemic toxins that may modulate cytochrome P450 enzyme activity and decrease glomerular filtration as well as tubular secretion. The general principles to enhance the safety of drug therapy in patients with renal insufficiency include knowledge of the potential toxicities and interactions of the therapeutic agent, consideration of possible alternatives therapies and individualisation of drug therapy based on patient level of renal function. Although optimisation of the desired therapeutic outcomes are of paramount importance, additional pharmacotherapeutic issues for patients with reduced renal function are the prevention or minimisation of future acute or chronic nephrotoxic insults, as well as the severity and occurrence of adverse effects on other organ systems. Risk factors for the development of nephrotoxicity for selected high-risk therapies (e.g. aminoglycosides, nonsteroidal anti-inflammatory drugs, ACE inhibitors and radiographic contrast media) are quite similar and include pre-existing renal insufficiency, concomitant administration of other nephrotoxins, volume depletion and concomitant hepatic disease or congestive heart failure. Investigations of prophylactic approaches to enhance the safety of these agents in patients with renal insufficiency have yielded inconsistent outcomes. Hydration with saline prior to drug exposure has given the most consistent benefit, while sodium

  8. Amorphous Silica Based Nanomedicine with Safe Carrier Excretion and Enhanced Drug Efficacy

    Science.gov (United States)

    Zhang, Silu

    With recent development of nanoscience and nanotechnology, a great amount of efforts have been devoted to nanomedicine development. Among various nanomaterials, silica nanoparticle (NP) is generally accepted as non-toxic, and can provide a versatile platform for drug loading. In addition, the surface of the silica NP is hydrophilic, being favorable for cellular uptake. Therefore, it is considered as one of the most promising candidates to serve as carriers for drugs. The present thesis mainly focuses on the design of silica based nanocarrier-drug systems, aiming at achieving safe nanocarrier excretion from the biological system and enhanced drug efficacy, which two are considered as most important issues in nanomedicine development. To address the safe carrier excretion issue, we have developed a special type of selfdecomposable SiO2-drug composite NPs. By creating a radial concentration gradient of drug in the NP, the drug release occurred simultaneously with the silica carrier decomposition. Such unique characteristic was different from the conventional dense SiO2-drug NP, in which drug was uniformly distributed and can hardly escape the carrier. We found that the controllable release of the drug was primarily determined by diffusion, which was caused by the radial drug concentration gradient in the NP. Escape of the drug molecules then triggered the silica carrier decomposition, which started from the center of the NP and eventually led to its complete fragmentation. The small size of the final carrier fragments enabled their easy excretion via renal systems. Apart from the feature of safe carrier excretion, we also found the controlled release of drugs contribute significantly to the drug efficacy enhancement. By loading an anticancer drug doxorubicin (Dox) to the decomposable SiO 2-methylene blue (MB) NPs, we achieved a self-decomposable SiO 2(MB)-Dox nanomedicine. The gradual escape of drug molecules from NPs and their enabled cytosolic release by optical

  9. Renal tubular function in children with beta-thalassemia minor.

    Science.gov (United States)

    Kalman, Süleyman; Atay, A Avni; Sakallioglu, Onur; Ozgürtaş, Taner; Gök, Faysal; Kurt, Ismail; Kürekçi, A Emin; Ozcan, Okan; Gökçay, Erdal

    2005-10-01

    beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

  10. Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Holstein-Rathlou, N H

    2001-01-01

    To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits...... sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P Renal free water clearance increased during WI in control subjects but not in HF......, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast...

  11. Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation.

    Science.gov (United States)

    Kawai, Yoshiko; Taniuchi, Saburo; Okahara, Shigeki; Nakamura, Masuhisa; Gemba, Munekazu

    2005-08-01

    Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation. Kidney tissue accumulation of cisplatin administered at 3.75 mg/kg was similar to that of nedaplatin administered at 24 mg/kg. At these doses, the plasma creatinine level and urinary excretion of glucose and N-acetyl-beta-D-glucosaminidase (NAG) similarly increased. There was a correlation between kidney accumulation of cisplatin and nedaplatin and the increases in plasma creatinine level and urinary excretion of NAG. Therefore, our results suggest that nedaplatin less frequently causes renal toxicity in comparison to cisplatin due to lower kidney accumulation.

  12. [Renal markers and predictors, and renal and cardiovascular risk factors].

    Science.gov (United States)

    Fernández-Andrade, C

    2002-01-01

    prediction. And also, its possible association nexuses, its injuring mechanisms, and the characterization of the new "emergent" renal and cardiovascular risk's markers and factors. 4. The impact on the possibility to treat the end stage renal disease with effective and prolonged procedures, by hemodialisis or kidney transplantation, has been occurred. The affected population's survival with the adequacy renal-sustitution treatment, and the possibility of indefinite duration of its treatment, has also impacted on the public health, and its resources, in an evident way. Simultaneously to increase of the incidence in the population, the electivity for the treatment has been enlarged and extended increasing it exponentially. These facts are documented here, and are defined the characteristics of the factors and markers of risk, of renal and cardiovascular diseases. The defined factors are valued to mark, so far as with the well-known evidence is possible, the prediction and the progression of the renal and cardiovascular functional deterioration: The hypertension, cardiovascular remodeling, the arterial stiffness, the heart rate, the sympathetic activation, the modification of the physiological response of the target organ to the overcharge, the metabolic syndrome, the obesity, the insulin resistance, the altered lipid profile, and metabolism of the fatty acids, the salt-sensibility, the decrease of the renal functional reserve, the glomerular hyperfiltration, the absence of the arterial pressure nocturnal descent, the abnormal excretion of proteins for the urine, the phenomenon induced by dysfunctions of the clotting, superoxide production, growth factors, the production of chronic inflammation and its markers, the factors of the glomerulosclerosis progression, the hyperuricemic status, the endothelial dysfunction and others, are evaluated. As well as their association among them and with other factors of risk not changeable like the age, and in turn, with other acquired

  13. Ureteral growth in animal models with increased renal excretion of urine

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    1999-01-01

    The influence of increased functional load on the macroscopical and histological appearance of the ureter was investigated. Sixty rats were divided into five groups: (1) sucrose-fed rats with non-osmotic polyuria; (2) diabetic rats with osmotic polyuria; (3) uninephrectomized rats; (4) sham-opera...

  14. Inactivation of extrahepatic vascular Akt improves systemic hemodynamics and sodium excretion in cirrhotic rats.

    Science.gov (United States)

    Fernández-Varo, G; Melgar-Lesmes, P; Casals, G; Pauta, M; Arroyo, V; Morales-Ruiz, M; Ros, J; Jiménez, W

    2010-12-01

    Increased activity of the vascular Akt/eNOS signaling pathway is involved in the hemodynamic and renal complications developed by patients and rats with cirrhosis and ascites. This occurs in the setting of impaired Akt/eNOS activity within the cirrhotic liver. Here we assessed the feasibility of selectively inhibiting vascular eNOS without further impairing the intrahepatic activity of this enzyme. Ultimately, we sought to determine whether endothelial transduction of a constitutively inactive mutant of Akt (AA-Akt) improves circulatory function and sodium excretion in cirrhotic rats with ascites. First, we administered recombinant adenoviruses that encode the β-galactosidase gene (β-gal) to 5 control rats and 5 cirrhotic rats with ascites and analyzed their tissue distribution by chemiluminescence. Next, urine samples were obtained from 18 cirrhotic rats with ascites and then the animal randomly received saline or adenoviruses containing the β-gal or the AA-Akt genes. Following a 24-h urine collection period, hemodynamic studies were performed and tissue samples were obtained to analyze Akt and eNOS expressions. No β-gal activity was detected in the liver of cirrhotic rats compared to that of controls. This was paralleled by increased β-gal activity in other territories such as the thoracic aorta. AA-Akt transduction improved systemic hemodynamics, splanchnic perfusion pressure and renal excretory function in comparison with cirrhotic rats transduced with β-gal adenoviruses or receiving saline. Moreover, the AA-Akt transgene did not modify portal pressure. Inactivation of extrahepatic vascular Akt and the concomitant decrease in nitric oxide expression ameliorate systemic hemodynamics and renal excretory function in experimental cirrhosis. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

    Directory of Open Access Journals (Sweden)

    Marcelo Roberto Choi

    2014-01-01

    Full Text Available Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways.

  16. Renal dopaminergic defect in C57Bl/6J mice.

    Science.gov (United States)

    Escano, Crisanto S; Armando, Ines; Wang, Xiaoyan; Asico, Laureano D; Pascua, Annabelle; Yang, Yu; Wang, Zheng; Lau, Yuen-Sum; Jose, Pedro A

    2009-12-01

    The C57Bl/6J mouse strain, the genetic background of many transgenic and gene knockout models, is salt sensitive and resistant to renal injury. We tested the hypothesis that renal dopaminergic function is defective in C57Bl/6J mice. On normal NaCl (0.8%, 1 wk) diet, anesthetized and conscious (telemetry) blood pressures were similar in C57Bl/6J and SJL/J mice. High NaCl (6%, 1 wk) increased blood pressure (approximately 30%) in C57Bl/6J but not in SJL/J mice and urinary dopamine to greater extent in SJL/J than in C57Bl/6J mice. Absolute and fractional sodium excretions were lower in SJL/J than in C57Bl/6J mice. The blood pressure-natriuresis plot was shifted to the right in C57Bl/6J mice. Renal expressions of D(1)-like (D(1)R and D(5)R) and angiotensin II AT(1) receptors were similar on normal salt, but high salt increased D(5)R only in C57Bl/6J. GRK4 expression was lower on normal but higher on high salt in C57Bl/6J than in SJL/J mice. Salt increased the excretion of microalbumin and 8-isoprostane (oxidative stress marker) and the degree of renal injury to a greater extent in SJL/J than in C57Bl/6J mice. A D(1)-like receptor agonist increased sodium excretion whereas a D(1)-like receptor antagonist decreased sodium excretion in SJL/J but not in C57Bl/6J mice. In contrast, parathyroid hormone had a similar natriuretic effect in both strains. These results show that defective D(1)-like receptor function is a major cause of salt sensitivity in C57Bl/6J mice, decreased renal dopamine production might also contribute. The relative resistance to renal injury of C57Bl/6J may be a consequence of decreased production of reactive oxygen species.

  17. Changes in parasite transmission stage excretion after pheasant release.

    Science.gov (United States)

    Villanúa, D; Acevedo, P; Höfle, U; Rodríguez, O; Gortázar, C

    2006-09-01

    The production of parasite transmission stages was investigated in the faeces of 77 farm-bred ring-necked pheasants (Phasianus colchicus). Coccidian oocysts (Eimeria sp.), and nematode eggs (Heterakis sp., and Capillaria-like eggs) were recovered before and after release but all birds were treated prior to release. Treatment with fenbendazole significantly reduced the abundance of transmission-stage excretion for all parasites, and reduced the prevalence in the case of Eimeria sp. and Heterakis sp. Nonetheless, a significant increase in the excretion abundance for all parasites and in the prevalence of Eimeria sp. and Heterakis sp. was found after release. Eggs of Ascaridia sp. were found only after releasing, suggesting infection ocurred in the wild. A negative relationship was found between the pheasant body condition and Heterakis excretion abundance and a higher abundance of Capillaria sp. eggs in female birds. No significant relationship was found between parasite excretion abundance and pheasant survival. Despite this, results suggest that an increase in the excretion of parasite transmission stages follows the release of captive pheasants into the wild. This can in part explain restocking failures, but also means that autochtonous free-living birds may become exposed to new and potentially harmful pathogens. To avoid these risks it is proposed that improved prophylactic measures should be taken.

  18. Iron deficiency anemia and increased urinary norepinephrine excretion.

    Science.gov (United States)

    Voorhess, M L; Stuart, M J; Stockman, J A; Oski, F A

    1975-04-01

    Chronic iron deficiency in rats resulted in decreased MAO activity both in vitro and in vivo. Since MAO is an important enzyme in inactivation of catecholamines, urinary excretion of DA, NE, E, MN-NMN, and VMA was measured in 24-hour samples from 11 iron-deficient children before and after treatment with intramuscular iron. Pretreatment NE excretion was abnormally high and returned to normal (P=0.001) within one week of therapy. VMA excretion also was higher before than after treatment (P greater than 0.05), but most values were within the normal range for healthy children of comparable size. There was no significant difference between DA, E, and MN-NMN excretion before and after iron therapy. Anemic, non-iron-deficient children had normal urinary NE, E, and VMA excretion before and after transfusion. These findings suggest that the irritability, lack of attentiveness, and low performance scores of iron-deficient children may be related to alterations in catecholamine metabolic pathways secondary to dependence of MAO on adequate iron stores.

  19. Urine excretion strategy for stem cell-generated embryonic kidneys

    Science.gov (United States)

    Yokote, Shinya; Matsunari, Hitomi; Iwai, Satomi; Yamanaka, Shuichiro; Uchikura, Ayuko; Fujimoto, Eisuke; Matsumoto, Kei; Nagashima, Hiroshi; Kobayashi, Eiji; Yokoo, Takashi

    2015-01-01

    There have been several recent attempts to generate, de novo, a functional whole kidney from stem cells using the organogenic niche or blastocyst complementation methods. However, none of these attempts succeeded in constructing a urinary excretion pathway for the stem cell-generated embryonic kidney. First, we transplanted metanephroi from cloned pig fetuses into gilts; the metanephroi grew to about 3 cm and produced urine, although hydronephrosis eventually was observed because of the lack of an excretion pathway. Second, we demonstrated the construction of urine excretion pathways in rats. Rat metanephroi or metanephroi with bladders (developed from cloacas) were transplanted into host rats. Histopathologic analysis showed that tubular lumina dilation and interstitial fibrosis were reduced in kidneys developed from cloacal transplants compared with metanephroi transplantation. Then we connected the host animal’s ureter to the cloacal-developed bladder, a technique we called the “stepwise peristaltic ureter” (SWPU) system. The application of the SWPU system avoided hydronephrosis and permitted the cloacas to differentiate well, with cloacal urine being excreted persistently through the recipient ureter. Finally, we demonstrated a viable preclinical application of the SWPU system in cloned pigs. The SWPU system also inhibited hydronephrosis in the pig study. To our knowledge, this is the first report showing that the SWPU system may resolve two important problems in the generation of kidneys from stem cells: construction of a urine excretion pathway and continued growth of the newly generated kidney. PMID:26392557

  20. Urinary carnitine excretion in surgical patients on total parenteral nutrition.

    Science.gov (United States)

    Tanphaichitr, V; Lerdvuthisopon, N

    1981-01-01

    Urinary free and total carnitine excretions were measured in 41 normal adults and seven surgical patients on fat-free total parenteral nutrition for 8 to 45 days. The means (+/-SEM) of urinary free and total carnitine excretion in normal adults were 162 +/- 19 and 328 +/- 28 micrometers/days, respectively. All of the patients exhibited protein-calorie malnutrition with a mean carnitine intake of 11.6 +/- 1.5 micrometers/day. Under this stringent carnitine economy with the adequate supply of lysine and methionine, urinary total carnitine excretion significantly reduced to 127 to 162 micrometers/day. This probably reflects the carnitine biosynthetic rate. However, during the periods of operation and/or infection, urinary total carnitine excretion significantly increased 2- to 7-fold that of normal levels. Significant positive correlation was found between the two forms of urinary carnitine and total nitrogen excretions. Serum free and total carnitine levels in patients were significantly higher than normal adults. Such findings can be explained by the endocrine responses to the stress phenomenon and indicate a catabolic response of skeletal muscle in which most of the body carnitine resides. This can impair their carnitine status.