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Sample records for links renal reabsorption

  1. Tubular reabsorption in normal renal function.

    PubMed

    O'Connor, W J

    1984-01-01

    The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption: (1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorption of Na. This would amount to the reabsorption by the tubules of a net reabsorbate of a composition similar to Locke's fluid. Fixed linkage of the reabsorption of a substance to the reabsorption of Na would be a very effective way of maintaining its plasma concentration within a narrow range. The substance would be retained unless its plasma concentration exceeds a threshold value and then small increase in plasma concentration determines its excretion. (2) The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals. Trying to see 'how far the observed facts can be brought into accord with a theory' reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.

  2. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice

    PubMed Central

    Corpe, Christopher P.; Tu, Hongbin; Eck, Peter; Wang, Jin; Faulhaber-Walter, Robert; Schnermann, Jurgen; Margolis, Sam; Padayatty, Sebastian; Sun, He; Wang, Yaohui; Nussbaum, Robert L.; Espey, Michael Graham; Levine, Mark

    2010-01-01

    Levels of the necessary nutrient vitamin C (ascorbate) are tightly regulated by intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Ascorbate levels are controlled in part by regulation of transport through at least 2 sodium-dependent transporters: Slc23a1 and Slc23a2 (also known as Svct1 and Svct2, respectively). Previous work indicates that Slc23a2 is essential for viability in mice, but the roles of Slc23a1 for viability and in adult physiology have not been determined. To investigate the contributions of Slc23a1 to plasma and tissue ascorbate concentrations in vivo, we generated Slc23a1–/– mice. Compared with wild-type mice, Slc23a1–/– mice increased ascorbate fractional excretion up to 18-fold. Hepatic portal ascorbate accumulation was nearly abolished, whereas intestinal absorption was marginally affected. Both heterozygous and knockout pups born to Slc23a1–/– dams exhibited approximately 45% perinatal mortality, and this was associated with lower plasma ascorbate concentrations in dams and pups. Perinatal mortality of Slc23a1–/– pups born to Slc23a1–/– dams was prevented by ascorbate supplementation during pregnancy. Taken together, these data indicate that ascorbate provided by the dam influenced perinatal survival. Although Slc23a1–/– mice lost as much as 70% of their ascorbate body stores in urine daily, we observed an unanticipated compensatory increase in ascorbate synthesis. These findings indicate a key role for Slc23a1 in renal ascorbate absorption and perinatal survival and reveal regulation of vitamin C biosynthesis in mice. PMID:20200446

  3. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice.

    PubMed

    Corpe, Christopher P; Tu, Hongbin; Eck, Peter; Wang, Jin; Faulhaber-Walter, Robert; Schnermann, Jurgen; Margolis, Sam; Padayatty, Sebastian; Sun, He; Wang, Yaohui; Nussbaum, Robert L; Espey, Michael Graham; Levine, Mark

    2010-04-01

    Levels of the necessary nutrient vitamin C (ascorbate) are tightly regulated by intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Ascorbate levels are controlled in part by regulation of transport through at least 2 sodium-dependent transporters: Slc23a1 and Slc23a2 (also known as Svct1 and Svct2, respectively). Previous work indicates that Slc23a2 is essential for viability in mice, but the roles of Slc23a1 for viability and in adult physiology have not been determined. To investigate the contributions of Slc23a1 to plasma and tissue ascorbate concentrations in vivo, we generated Slc23a1-/- mice. Compared with wild-type mice, Slc23a1-/- mice increased ascorbate fractional excretion up to 18-fold. Hepatic portal ascorbate accumulation was nearly abolished, whereas intestinal absorption was marginally affected. Both heterozygous and knockout pups born to Slc23a1-/- dams exhibited approximately 45% perinatal mortality, and this was associated with lower plasma ascorbate concentrations in dams and pups. Perinatal mortality of Slc23a1-/- pups born to Slc23a1-/- dams was prevented by ascorbate supplementation during pregnancy. Taken together, these data indicate that ascorbate provided by the dam influenced perinatal survival. Although Slc23a1-/- mice lost as much as 70% of their ascorbate body stores in urine daily, we observed an unanticipated compensatory increase in ascorbate synthesis. These findings indicate a key role for Slc23a1 in renal ascorbate absorption and perinatal survival and reveal regulation of vitamin C biosynthesis in mice.

  4. Renal sodium reabsorption after acute renal denervation in the rabbit

    PubMed Central

    Blake, William D.; Jurf, Amin N.

    1968-01-01

    1. Separate effects on the functions of left and right kidneys were examined after left-sided renal handling and acute denervation. Studies were done on pentobarbital-anaesthetized rabbits using clearance techniques to evaluate renal haemodynamics and water and electrolyte excretion. 2. When compared with its counterpart, the handled kidney exhibited some decrease in function for at least 20 min. Recovery of most functions occurred in 40-60 min. 3. The effects of denervation on renal functions were observed when the effects of handling had subsided. Renal plasma flow (R.P.F.) and glomerular filtration rate (G.F.R.) were not significantly changed, whereas the decrease in Na, K and water excretion, which was usually observed for no ascertained reason in the innervated kidney, was prevented. 4. The magnitude of the denervation natriuresis was greater in these rabbits than in dogs studied previously; other functions studied were comparable in the two species. 5. The results from thirty-five experiments are interpreted to indicate that denervation decreases Na reabsorption independently of G.F.R., perhaps by a direct effect on tubular transport, but more probably by a redistribution of filtration to nephrons of lesser reabsorptive capacity. PMID:5653887

  5. Intestinal absorption and renal reabsorption of calcium throughout postnatal development

    PubMed Central

    Beggs, Megan R

    2017-01-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  6. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    PubMed

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  7. Angiotensin II natriuresis and antinatriuresis: role of renal artery pressure, renal hemodynamics, and tubular reabsorption.

    PubMed

    Olsen, M E; Hall, J E; Montani, J P; Guyton, A C

    1985-01-01

    The aim of this study was to determine the role of changes in renal artery pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (AII). In anesthetized dogs, endogenous AII formation was blocked with SQ-14225 and AII was infused i.v. at rates of 5-1215 ng/kg/min while RAP was either servo-controlled at the normal level or permitted to increase. When RAP was servo-controlled to prevent a rise i RAP, AII infusion at all rates from 5-1215 ng/kg/min decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa), while increasing fractional reabsorption of lithium (FRLi), an index of proximal tubule fractional sodium reabsorption and distal fractional sodium reabsorption (FRDNa): When RAP was permitted to increase, AII infusion rates up to 45 ng/kg/min decreased UNaV, and FENa, while increasing FRLi and FRDNa. However, at 135 ng/kg/min and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though RBF and FF were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during AII infusion, compared to the dogs in which RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of AII cause antinatriuresis when RAP was prevented from increasing. The natriuretic effect of high dose of AII is caused by increased RAP which decreases fractional sodium reabsorption in proximal and distal tubules and causes slight increases in sodium delivery to the tubules.

  8. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption.

    PubMed

    Birn, H; Fyfe, J C; Jacobsen, C; Mounier, F; Verroust, P J; Orskov, H; Willnow, T E; Moestrup, S K; Christensen, E I

    2000-05-01

    Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

  9. Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans

    NASA Technical Reports Server (NTRS)

    Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

    2001-01-01

    We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

  10. Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans

    NASA Technical Reports Server (NTRS)

    Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

    2001-01-01

    We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

  11. Renal Sodium- and Potassium-Activated Adenosine Triphosphatase and Sodium Reabsorption in the Hypothyroid Rat

    PubMed Central

    Katz, Adrian I.; Lindheimer, Marshall D.

    1973-01-01

    The relationship between net tubular reabsorption of sodium and renal microsomal sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186±14 vs. 246±12 μeq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4±2.4 vs. 65.8±2.3 μmol inorganic phosphate (Pt)/mg protein per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5′-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 10-12 to 10-5 M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intact controls. Despite persistence of the hypothyroid state, Na-K-ATPase specific activity also increased to levels not significantly different from euthyroid animals. These data suggest that decreased tubular sodium transport is a major determinant of the reduction in renal Na-K-ATPase in thyroid deficiency since the latter can be reversed by increasing sodium reabsorption during continuing hypothyroidism. Furthermore, the modest sodium leak of hypothyroid animals does not appear to

  12. Cubilin Is Essential for Albumin Reabsorption in the Renal Proximal Tubule

    PubMed Central

    Amsellem, Sabine; Gburek, Jakub; Hamard, Ghislaine; Nielsen, Rikke; Willnow, Thomas E.; Devuyst, Olivier; Nexo, Ebba; Verroust, Pierre J.

    2010-01-01

    Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the “specific” cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases. PMID:20798259

  13. Cubilin is essential for albumin reabsorption in the renal proximal tubule.

    PubMed

    Amsellem, Sabine; Gburek, Jakub; Hamard, Ghislaine; Nielsen, Rikke; Willnow, Thomas E; Devuyst, Olivier; Nexo, Ebba; Verroust, Pierre J; Christensen, Erik I; Kozyraki, Renata

    2010-11-01

    Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the "specific" cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases.

  14. Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na(+) and restricted dietary Na().

    PubMed

    Alshahrani, Saeed; Rapoport, Robert M; Soleimani, Manoocher

    2017-03-01

    Reduced renal Na(+) reabsorption along with restricted dietary Na(+) depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na(+) reabsorption and restricted dietary Na(+) associated with considerable hypotension and renin-angiotensin system activation: (1) the Na(+)-Cl(-)-Co-transporter (NCC) knockout (KO) with Na(+) restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na(+)-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na(+)-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na(+) reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.

  15. A Model of Peritubular Capillary Control of Isotonic Fluid Reabsorption by the Renal Proximal Tubule

    PubMed Central

    Deen, W. M.; Robertson, C. R.; Brenner, B. M.

    1973-01-01

    A mathematical model of peritubular transcapillary fluid exchange has been developed to investigate the role of the peritubular environment in the regulation of net isotonic fluid transport across the mammalian renal proximal tubule. The model, derived from conservation of mass and the Starling transcapillary driving forces, has been used to examine the quantitative effects on proximal reabsorption of changes in efferent arteriolar protein concentration and plasma flow rate. Under normal physiological conditions, relatively small perturbations in protein concentration are predicted to influence reabsorption more than even large variations in plasma flow, a prediction in close accord with recent experimental observations in the rat and dog. Changes either in protein concentration or plasma flow have their most pronounced effects when the opposing transcapillary hydrostatic and osmotic pressure differences are closest to equilibrium. Comparison of these theoretical results with variations in reabsorption observed in micropuncture studies makes it possible to place upper and lower bounds on the difference between interstitial oncotic and hydrostatic pressures in the renal cortex of the rat. PMID:4696761

  16. Renal carbonic anhydrases are involved in the reabsorption of endogenous nitrite.

    PubMed

    Chobanyan-Jürgens, Kristine; Schwarz, Alexandra; Böhmer, Anke; Beckmann, Bibiana; Gutzki, Frank-Mathias; Michaelsen, Jan T; Stichtenoth, Dirk O; Tsikas, Dimitrios

    2012-02-15

    Nitrite (ONO(-)) exerts nitric oxide (NO)-related biological actions and its concentration in the circulation may be of particular importance. Nitrite is excreted in the urine. Hence, the kidney may play an important role in nitrite/NO homeostasis in the vasculature. We investigated a possible involvement of renal carbonic anhydrases (CAs) in endogenous nitrite reabsorption in the proximal tubule. The potent CA inhibitor acetazolamide was administered orally to six healthy volunteers (5 mg/kg) and nitrite was measured in spot urine samples before and after administration. Acetazolamide increased abruptly nitrite excretion in the urine, strongly suggesting that renal CAs are involved in nitrite reabsorption in healthy humans. Additional in vitro experiments support our hypothesis that nitrite reacts with CO(2), analogous to the reaction of peroxynitrite (ONOO(-)) with CO(2), to form acid-labile nitrito carbonate [ONOC(O)O(-)]. We assume that this reaction is catalyzed by CAs and that nitrito carbonate represents the nitrite form that is actively transported into the kidney. The significance of nitrite reabsorption in the kidney and the underlying mechanisms, notably a direct involvement of CAs in the reaction between nitrite and CO(2), remain to be elucidated.

  17. Aromatase Deficient Female Mice Demonstrate Altered Expression of Molecules Critical for Renal Calcium Reabsorption

    NASA Astrophysics Data System (ADS)

    Öz, Orhan K.; Hajibeigi, Asghar; Cummins, Carolyn; van Abel, Monique; Bindels, René J.; Kuro-o, Makoto; Pak, Charles Y. C.; Zerwekh, Joseph E.

    2007-04-01

    The incidence of kidney stones increases in women after the menopause, suggesting a role for estrogen deficiency. In order to determine if estrogen may be exerting an effect on renal calcium reabsorption, we measured urinary calcium excretion in the aromatase-deficient female mouse (ArKO) before and following estrogen therapy. ArKO mice had hypercalciuria that corrected during estrogen administration. To evaluate the mechanism by which estrogen deficiency leads to hypercalciuria, we examined the expression of several proteins involved in distal tubule renal calcium reabsorption, both at the message and protein levels. Messenger RNA levels of TRPV5, TRPV6, calbindin-D28K, the Na+/Ca++ exchanger (NCX1), and the plasma membrane calcium ATPase (PMCA1b) were significantly decreased in kidneys of ArKO mice. On the other hand, klotho mRNA levels were elevated in kidneys of ArKO mice. ArKO renal protein extracts had lower levels of calbindin-D28K but higher levels of the klotho protein. Immunochemistry demonstrated increased klotho expression in ArKO kidneys. Estradiol therapy normalized the expression of TRPV5, calbindin-D28K, PMCA1b and klotho. Taken together, these results demonstrate that estrogen deficiency produced by aromatase inactivation is sufficient to produce a renal leak of calcium and consequent hypercalciuria. This may represent one mechanism leading to the increased incidence of kidney stones following the menopause in women.

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

    PubMed

    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.

  19. Electro-osmosis and the reabsorption of fluid in renal proximal tubules

    PubMed Central

    1985-01-01

    The lateral intercellular spaces (LIS) are believed to be the final common pathway for fluid reabsorption from the renal proximal tubule. We postulate that electrogenic sodium pumps in the lateral membranes produce an electrical potential within the LIS, that the lateral membranes bear a net negative charge, and that fluid moves parallel to these membranes because of Helmholtz-type electro-osmosis, the field- induced movement of fluid adjacent to a charged surface. Our theoretical analysis indicates that the sodium pumps produce a longitudinal electric field of the order of 1 V/cm in the LIS. Our experimental measurements demonstrate that the electrophoretic mobility of rat renal basolateral membrane vesicles is 1 micron/s per V/cm, which is also the electro-osmotic fluid velocity in the LIS produced by a unit electric field. Thus, the fluid velocity in the LIS due to electro-osmosis should be of the order of 1 micron/s, which is sufficient to account for the observed reabsorption of fluid from renal proximal tubules. Several experimentally testable predictions emerge from our model. First, the pressure in the LIS need not increase when fluid is transported. Thus, the LIS of mammalian proximal tubules need not swell during fluid transport, a prediction consistent with the observations of Burg and Grantham (1971, Membranes and Ion Transport, pp. 49-77). Second, the reabsorption of fluid is predicted to cease when the lumen is clamped to a negative voltage. Our analysis predicts that a voltage of -15 mV will cause fluid to be secreted into the Necturus proximal tubule, a prediction consistent with the observations of Spring and Paganelli (1972, J. Gen. Physiol., 60:181). PMID:3998707

  20. Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process

    PubMed Central

    Subramanian, Veedamali S.; Subramanya, Sandeep B.

    2011-01-01

    Normal body homeostasis of biotin is critically dependent on its renal recovery by kidney proximal tubular epithelial cells, a process that is mediated by the sodium-dependent multivitamin transporter (SMVT; a product of the SLC5A6 gene). Chronic ethanol consumption interferes with the renal reabsorption process of a variety of nutrients, including water-soluble vitamins. To date, however, there is nothing known about the effect of chronic alcohol feeding on physiological and molecular parameters of the renal biotin reabsorption process. We addressed these issues using rats and transgenic mice carrying the human SLC5A6 (P1P2) 5′-regulatory region as an in vivo model systems of alcohol exposure, and cultured human renal proximal tubular epithelial HK-2 cells chronically exposed to alcohol as an in vitro model of alcohol exposure. The [3H]biotin uptake results showed that chronic ethanol feeding in rats leads to a significant inhibition in carrier-mediated biotin transport across both renal brush border and basolateral membrane domains. This inhibition was associated with a marked reduction in the level of expression of SMVT protein, mRNA, and heterogenous nuclear RNA (hnRNA). Furthermore, studies with transgenic mice carrying the SLC5A6 5′-regulatory region showed that chronic alcohol feeding leads to a significant decrease in promoter activity. Studies with HK-2 cells chronically exposed to alcohol again showed a marked reduction in carrier-mediated biotin uptake, which was associated with a significant reduction in promoter activity of the human SLC5A6 5′-regulatory region. These findings demonstrate for the first time that chronic ethanol feeding inhibits renal biotin transport and that this effect is, at least in part, being exerted at the transcriptional level. PMID:21209005

  1. Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process.

    PubMed

    Subramanian, Veedamali S; Subramanya, Sandeep B; Said, Hamid M

    2011-03-01

    Normal body homeostasis of biotin is critically dependent on its renal recovery by kidney proximal tubular epithelial cells, a process that is mediated by the sodium-dependent multivitamin transporter (SMVT; a product of the SLC5A6 gene). Chronic ethanol consumption interferes with the renal reabsorption process of a variety of nutrients, including water-soluble vitamins. To date, however, there is nothing known about the effect of chronic alcohol feeding on physiological and molecular parameters of the renal biotin reabsorption process. We addressed these issues using rats and transgenic mice carrying the human SLC5A6 (P1P2) 5'-regulatory region as an in vivo model systems of alcohol exposure, and cultured human renal proximal tubular epithelial HK-2 cells chronically exposed to alcohol as an in vitro model of alcohol exposure. The [(3)H]biotin uptake results showed that chronic ethanol feeding in rats leads to a significant inhibition in carrier-mediated biotin transport across both renal brush border and basolateral membrane domains. This inhibition was associated with a marked reduction in the level of expression of SMVT protein, mRNA, and heterogenous nuclear RNA (hnRNA). Furthermore, studies with transgenic mice carrying the SLC5A6 5'-regulatory region showed that chronic alcohol feeding leads to a significant decrease in promoter activity. Studies with HK-2 cells chronically exposed to alcohol again showed a marked reduction in carrier-mediated biotin uptake, which was associated with a significant reduction in promoter activity of the human SLC5A6 5'-regulatory region. These findings demonstrate for the first time that chronic ethanol feeding inhibits renal biotin transport and that this effect is, at least in part, being exerted at the transcriptional level.

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

    PubMed Central

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

    2009-01-01

    This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg·kg−1·min−1 iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging ∼20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs. PMID:19073906

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

    PubMed

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

    2009-02-01

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

  4. Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

    PubMed Central

    Burford, James L.; McDonough, Alicia A.; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

    2014-01-01

    The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution. PMID:25298526

  5. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.

    PubMed

    Vallon, Volker; Thomson, Scott C

    2017-02-01

    Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule. In the absence or with inhibition of SGLT2, the renal reabsorptive capacity for glucose declines to ∼80 g/day (the residual capacity of SGLT1), i.e. the safety valve opens at a lower threshold, which makes it relevant to glucose homeostasis from day-to-day. Several SGLT2 inhibitors are now approved glucose lowering agents for individuals with type 2 diabetes and preserved kidney function. By inducing glucosuria, these drugs improve glycaemic control in all stages of type 2 diabetes, while their risk of causing hypoglycaemia is low because they naturally stop working when the filtered glucose load falls below ∼80 g/day and they do not otherwise interfere with metabolic counterregulation. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. Because SGLT2 reabsorbs sodium along with glucose, SGLT2 blockers are natriuretic and antihypertensive. Also, because they work in the proximal tubule, SGLT2 inhibitors increase delivery of fluid and electrolytes to the macula densa, thereby activating tubuloglomerular feedback and increasing tubular back pressure. This mitigates glomerular hyperfiltration, reduces the kidney's demand for oxygen and lessens albuminuria. For reasons that are less well understood, SGLT2 inhibitors are

  6. Semi-mechanistic kidney model incorporating physiologically-relevant fluid reabsorption and transporter-mediated renal reabsorption: Pharmacokinetics of γ-hydroxybutyric acid and L-lactate in rats

    PubMed Central

    Dave, Rutwij A.; Morris, Marilyn E.

    2015-01-01

    This study developed a semi-mechanistic kidney model incorporating physiologically-relevant fluid reabsorption and transporter-mediated active reabsorption. The model was applied to data for the drug of abuse γ-hydroxybutyric acid (GHB), which exhibits monocarboxylate transporter (MCT1/SMCT1)-mediated renal reabsorption. The kidney model consists of various nephron segments – proximal tubules, Loop-of-Henle, distal tubules, and collecting ducts – where the segmental fluid flow rates, volumes, and sequential reabsorption were incorporated as functions of the glomerular filtration rate. The active renal reabsorption was modeled as vectorial transport across proximal tubule cells. In addition, the model included physiological blood, liver, and remainder compartments. The population pharmacokinetic modeling was performed using ADAPT5 for GHB blood concentration-time data and cumulative amount excreted unchanged into urine data (200–1000 mg/kg IV bolus doses) from rats (Felmlee et al (PMID: 20461486)). Simulations assessed the effects of inhibition (R=[I]/KI=0–100) of renal reabsorption on systemic exposure (AUC) and renal clearance of GHB. Visual predictive checks and other model diagnostic plots indicated that the model reasonably captured GHB concentrations. Simulations demonstrated that the inhibition of renal reabsorption significantly increased GHB renal clearance and decreased AUC. Model validation was performed using a separate dataset. Furthermore, our model successfully evaluated the pharmacokinetics of L-lactate using data obtained from Morse et al (PMID: 24854892). In conclusion, we developed a semi-mechanistic kidney model that can be used to evaluate transporter-mediated active renal reabsorption of drugs by the kidney. PMID:26341876

  7. Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway.

    PubMed

    Tang, Xiaojiang; Zhu, Jinqiu; Zhong, Zhiyong; Luo, Minhui; Li, Guangxian; Gong, Zhihong; Zhang, Chenzi; Fei, Fan; Ruan, Xiaolin; Zhou, Jinlin; Liu, Gaofeng; Li, Guoding; Olson, James; Ren, Xuefeng

    2016-08-15

    Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9μg/g to 1.3μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-11-01

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

  9. Interleukin-1 decreases renal sodium reabsorption: possible mechanism of endotoxin-induced natriuresis

    SciTech Connect

    Caverzasio, J.; Rizzoli, R.; Dayer, J.M.; Bonjour, J.P.

    1987-05-01

    Administration of pyrogen or endotoxins such as Escherichia coli lipopolysaccharide can elicit a marked increase in urinary sodium excretion. This response occurs without any elevation in the filtered load of sodium and it does not appear to be prostaglandin mediated. The various effects produced by endotoxins appear to have interleukin-1 as a common mediator. In the present work, the authors have studied whether human recombinant interleukin-1..beta.. (hrIL-1) could affect the renal handling of sodium and thus, could be implicated in natriuretic response to pyrogens or endotoxins. They observed that hrIL-1 intravenously injected into conscious rats provokes a marked increase in sodium excretion. This natriuretic response was not associated with any increase in glomerular filtration rate (clearance of (/sup 3/H)inulin), nor was it accompanied by significant changes in the urinary excretion of potassium, calcium, or inorganic phosphate. The only concomitant alteration was a decrease in urinary pH. Pretreatment with indomethacin abolished the effect of hrIL-1 on urinary pH but did not modify the natriuretic response. In conclusion, hrIL-1 elicits a selective decrease in tubular sodium reabsorption, which does not appear to involve a change in prostaglandin synthesis. This observation strongly suggests that interleukin-1 could be a key mediator in endotoxin-induced natriuresis.

  10. Impact of genetic knockout of PEPT2 on cefadroxil pharmacokinetics, renal tubular reabsorption, and brain penetration in mice.

    PubMed

    Shen, Hong; Ocheltree, Scott M; Hu, Yongjun; Keep, Richard F; Smith, David E

    2007-07-01

    The aim of this study was to examine the role of PEPT2, a proton-coupled oligopeptide transporter of the SLC15 family, on the disposition of the antibiotic cefadroxil in the body, particularly the kidney and brain. Pharmacokinetic, tissue distribution, and renal clearance studies were performed in wild-type and PEPT2 null mice after intravenous bolus administration of [(3)H]cefadroxil at 1, 12.5, 50, and 100 nmol/g body weight. Studies were also performed in the absence and presence of probenecid and quinine. Cefadroxil disposition kinetics was clearly nonlinear over the dose range studied (1-100 nmol/g), which was attributed to both saturable renal tubular secretion and reabsorption of the antibiotic. After an intravenous bolus dose of 1 nmol/g cefadroxil, PEPT2 null mice exhibited a 3-fold greater total clearance and 3-fold lower systemic concentrations of drug compared with wild-type animals. Renal clearance studies further demonstrated that the renal reabsorption of cefadroxil was almost completely abolished in PEPT2 null versus wild-type mice (3% versus 70%, p < 0.001). Of the 70% of cefadroxil reabsorbed in wild-type mice, PEPT2 accounted for 95% and PEPT1 accounted for 5% of reabsorbed substrate. Tissue distribution studies indicated that PEPT2 had a dramatic effect on cefadroxil tissue exposure, especially in brain where the cerebrospinal fluid (CSF)-to-blood concentration ratio of cefadroxil was 6-fold greater in PEPT2 null mice compared with wild-type animals. These findings demonstrate that renal PEPT2 is almost entirely responsible for the reabsorption of cefadroxil in kidney and that choroid plexus PEPT2 limits the exposure of cefadroxil (and perhaps other aminocephalosporins) in CSF.

  11. Renal tissue citrate: independence from citrate utilization, reabsorption, and pH.

    PubMed

    Anaizi, N H; Cohen, J J; Black, A J; Wertheim, S J

    1986-09-01

    During alkalosis in vivo, renal tissue [citrate] [( citrate]t) increases and citrate reabsorption (Tcit) and utilization (Qcit) simultaneously decrease. The decrease in Qcit is interpreted to cause the increased [citrate]t, which in turn decreases Tcit X Renal citrate handling and [citrate]t could be regulated by other mechanisms, since alkalosis changes [substrate] and [H+] in extracellular (ECF) and intracellular (ICF) fluid. Also, since high plasma [citrate] decreases ionized [Ca2+] (Cai), it is not possible to determine in vivo whether there is a maximum for Tcit or Qcit and whether change in extracellular fluid (delta ECF) pH affects these maxima. We perfused the substrate-limited isolated rat kidney for either 110 (n = 36) or 50 min (n = 44) at pH 7.2, 7.4, or 7.6; pH was changed by varying [HCO3-]; Cai was held constant at approximately 2.5 meq/liter. When citrate was the only substrate available in a Krebs-Ringer-HCO3 perfusate containing 6% substrate-free albumin, both Qcit and Tcit had maximal rates: Qcit much greater than Tcit; at pH 7.6, Qcit and Tcit were significantly reduced below their values at pH 7.2 or 7.4. In contrast to in vivo observations, [citrate]t was not significantly increased at high ECF pH. To test whether [citrate]t in the perfused kidney can increase in alkalosis, 11 additional perfusions were done in the presence of glucose plus lactate plus malate but without added citrate: [citrate]t = 0.6 mumol X g-1 at pH 7.6 and 0.3 mumol X g-1 at pH 7.2 (P less than 0.01); no citrate was detectable in the perfusate, and urinary citrate excretion was negligible. Thus, in the isolated rat kidney, an increase in [citrate]t occurred in alkalosis and was derived from precursors and not from citrate in the ECF. Overall, when only citrate was available to the isolated kidney during alkalosis, a significant rise in [citrate]t did not occur, although Vmax for Tcit and Qcit decreased. These effects of alkalosis on Tcit are consistent with observations

  12. Long-term regulation of arterial pressure, glomerular filtration and renal sodium reabsorption by angiotensin II in dogs.

    PubMed

    Hall, J E; Guyton, A C; Smith, M J; Coleman, T G

    1980-12-01

    1. This study was designed to quantify the role of angiotensin II in determining the chronic relationships between arterial pressure, renal haemodynamics and sodium excretion. 2. In six control dogs sodium balance was achieved during chronic increases in sodium intake from 5 to 495 mmol/day with small increases in arterial pressure (7mmHg), moderate increases in glomerular filtration rate (19%) and decreases in filtration fraction. Similar increases in sodium intake in dogs whose circulating levels of angiotensin II were fixed, due to a constant intravenous infusion of 4.85 pmol of angiotensin II min-1 kg-1, caused large increases in arterial pressure (42%), glomerular filtration rate (31%), filtration fraction and calculated renal sodium reabsorption above control. In six dogs whose angiotensin II formation was blocked by SQ 14 225, sodium balance at intakes of 5-80 mmol/day occurred at reduced arterial pressure, glomerular filtration rate, filtration fraction and sodium reabsorption although plasma aldosterone concentration was not substantially different from that in control dogs. At sodium intakes above 240 mmoL/day arterial pressure was not altered by SQ 14 225. 3. These data indicate that during chronic variations in sodium intake angiotensin II plays a major role, independently of changes in plasma aldosterone concentration, in allowing sodium balance without large fluctuations in glomerular filtration rate or arterial pressure. The mechanism whereby angiotensin II conserves sodium chronically is through increased sodium reabsorption, since steady-state sodium reabsorption was increased by angiotensin II and decreased by SQ 14 225.

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

    PubMed

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

    2014-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40-50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1-/-) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1-/- vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1-/- vs. WT after 24 h (-33 vs. -11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1-/-. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to -1 ± 3% in Sglt1-/-. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50-60% of filtered glucose is excreted.

  14. Topographically-patterned porous membranes in a microfluidic device as an in vitro model of renal reabsorptive barriers

    PubMed Central

    Frohlich, Else M.; Alonso, José Luis; Borenstein, Jeffrey T.; Zhang, Xin; Arnaout, M. Amin

    2015-01-01

    Models of reabsorptive barriers require both a means to provide realistic physiologic cues to and quantify transport across a layer of cells forming the barrier. Here we have topographically-patterned porous membranes with several user-defined pattern types. To demonstrate the utility of the patterned membranes, we selected one type of pattern and applied it to a membrane to serve as a cell culture support in a microfluidic model of a renal reabsorptive barrier. The topographic cues in the model resemble physiological cues found in vivo while the porous structure allows quantification of transport across the cell layer. Sub-micron surface topography generated via hot-embossing onto a track-etched polycarbonate membrane, fully replicated topographical features and preserved porous architecture. Pore size and shape were analyzed with SEM and image analysis to determine the effect of hot embossing on pore morphology. The membrane was assembled into a bilayer microfluidic device and a human kidney proximal tubule epithelial cell line (HK-2) and primary renal proximal tubule epithelial cells (RPTEC) were cultured to confluency on the membrane. Immunofluorescent staining of both cell types revealed protein expression indicative of the formation of a reabsorptive barrier responsive to mechanical stimulation: ZO-1 (tight junction), paxillin (focal adhesions) and acetylated α-tubulin (primary cilia). HK-2 and RPTEC aligned in the direction of ridge/groove topography of the membrane in the device, evidence that the device has mechanical control over cell response. This topographically-patterned porous membrane provides an in vitro platform on which to model reabsorptive barriers with meaningful applications for understanding biological transport phenomenon, underlying disease mechanisms, and drug toxicity. PMID:23636129

  15. Topographically-patterned porous membranes in a microfluidic device as an in vitro model of renal reabsorptive barriers.

    PubMed

    Frohlich, Else M; Alonso, José Luis; Borenstein, Jeffrey T; Zhang, Xin; Arnaout, M Amin; Charest, Joseph L

    2013-06-21

    Models of reabsorptive barriers require both a means to provide realistic physiologic cues to and quantify transport across a layer of cells forming the barrier. Here we have topographically-patterned porous membranes with several user-defined pattern types. To demonstrate the utility of the patterned membranes, we selected one type of pattern and applied it to a membrane to serve as a cell culture support in a microfluidic model of a renal reabsorptive barrier. The topographic cues in the model resemble physiological cues found in vivo while the porous structure allows quantification of transport across the cell layer. Sub-micron surface topography generated via hot-embossing onto a track-etched polycarbonate membrane, fully replicated topographical features and preserved porous architecture. Pore size and shape were analyzed with SEM and image analysis to determine the effect of hot embossing on pore morphology. The membrane was assembled into a bilayer microfluidic device and a human kidney proximal tubule epithelial cell line (HK-2) and primary renal proximal tubule epithelial cells (RPTEC) were cultured to confluency on the membrane. Immunofluorescent staining of both cell types revealed protein expression indicative of the formation of a reabsorptive barrier responsive to mechanical stimulation: ZO-1 (tight junction), paxillin (focal adhesions) and acetylated α-tubulin (primary cilia). HK-2 and RPTEC aligned in the direction of ridge/groove topography of the membrane in the device, evidence that the device has mechanical control over cell response. This topographically-patterned porous membrane provides an in vitro platform on which to model reabsorptive barriers with meaningful applications for understanding biological transport phenomenon, underlying disease mechanisms, and drug toxicity.

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

    PubMed Central

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

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted. PMID:24226519

  17. The relationship between the renal reabsorption of cysteine and the lowered urinary pH in diabetics.

    PubMed

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

    2017-03-22

    In diabetic patients, reduced urinary pH (UpH) is a predictive factor for cardiorenal-vascular disorders. Synthesis of glutathione, an anti-oxidative stress substance, is induced to counteract renal oxidative stress. UpH declines as glutamate is consumed, as does the synthesis of ammonia from glutamate. Glutathione is synthesized from glutamate and cysteine; however, in diabetes, the relationship between lowered UpH and the roles of renal amino acids is unknown. We, therefore, examined the relationship between amino-acid kinetics, UpH, and renal function. This cross-sectional study targeted 100 non-diabetic obese individuals (OG: obese group) and 100 diabetics (DG: diabetic group). We investigated their blood amino acids, urinary amino-acid excretion, the reabsorption rates of various amino acids, and their relationship with the UpH and estimated glomerular filtration rate (eGFR). The DG subjects showed higher blood cysteine concentration, urinary glutamate, and cysteine excretions than the OG subjects. Although the glutamate reabsorption rate declined in the DG subjects, that of cysteine increased due to the lowered eGFR. The DG subjects' urinary cysteine excretion correlated positively with UpH, making this urinary cysteine excretion the sole independent risk factor for lower UpH. In patients with diabetes, the reabsorbed amount of cysteine, not glutamate, regulates the amount of glutathione synthesis in the kidneys. The more an amount of cysteine reabsorption increases concurrently with a decline in eGFR, the more its urinary excretion decreases. Under these conditions, concurrently, the glutamate consumption then increases, resulting in decreased ammonia synthesis and UpH.

  18. The Cap1–claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation

    PubMed Central

    Gong, Yongfeng; Yu, Miao; Yang, Jing; Gonzales, Ernie; Perez, Ronaldo; Hou, Mingli; Tripathi, Piyush; Hering-Smith, Kathleen S.; Hamm, L. Lee; Hou, Jianghui

    2014-01-01

    The paracellular pathway through the tight junction provides an important route for transepithelial chloride reabsorption in the kidney, which regulates extracellular salt content and blood pressure. Defects in paracellular chloride reabsorption may in theory cause deregulation of blood pressure. However, there is no evidence to prove this theory or to demonstrate the in vivo role of the paracellular pathway in renal chloride handling. Here, using a tissue-specific KO approach, we have revealed a chloride transport pathway in the kidney that requires the tight junction molecule claudin-4. The collecting duct-specific claudin-4 KO animals developed hypotension, hypochloremia, and metabolic alkalosis due to profound renal wasting of chloride. The claudin-4–mediated chloride conductance can be regulated endogenously by a protease—channel-activating protease 1 (cap1). Mechanistically, cap1 regulates claudin-4 intercellular interaction and membrane stability. A putative cap1 cleavage site has been identified in the second extracellular loop of claudin-4, mutation of which abolished its regulation by cap1. The cap1 effects on paracellular chloride permeation can be extended to other proteases such as trypsin, suggesting a general mechanism may also exist for proteases to regulate the tight junction permeabilities. Together, we have discovered a theory that paracellular chloride permeability is physiologically regulated and essential to renal salt homeostasis and blood pressure control. PMID:25157135

  19. Teaching the Renal Tubular Reabsorption of Glucose Using Two Classic Papers by Shannon et al.

    ERIC Educational Resources Information Center

    Braga, Valdir A.

    2011-01-01

    Most of the transport along the nephron uses membrane proteins and exhibits the three characteristics of mediated transport: saturation, specificity, and competition. Glucose reabsorption in the nephron is an excellent example of the consequences of saturation. Two classic papers by James A. Shannon and colleagues clearly show the ability of the…

  20. Teaching the Renal Tubular Reabsorption of Glucose Using Two Classic Papers by Shannon et al.

    ERIC Educational Resources Information Center

    Braga, Valdir A.

    2011-01-01

    Most of the transport along the nephron uses membrane proteins and exhibits the three characteristics of mediated transport: saturation, specificity, and competition. Glucose reabsorption in the nephron is an excellent example of the consequences of saturation. Two classic papers by James A. Shannon and colleagues clearly show the ability of the…

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

    PubMed

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

    PubMed Central

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

    1986-01-01

    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. PMID:3722417

  3. Local pH domains regulate NHE3-mediated Na⁺ reabsorption in the renal proximal tubule.

    PubMed

    Brasen, Jens Christian; Burford, James L; McDonough, Alicia A; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

    2014-12-01

    The proximal tubule Na(+)/H(+) exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na(+) reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.

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

    PubMed

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

    2012-07-01

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

  5. Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat.

    PubMed

    Worley, Rachel Rogers; Fisher, Jeffrey

    2015-12-15

    Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. Published by Elsevier Inc.

  6. Application of Physiologically-Based Pharmacokinetic Modeling to Explore the Role of Kidney Transporters in Renal Reabsorption of Perfluorooctanoic Acid in the Rat

    PubMed Central

    Worley, Rachel Rogers; Fisher, Jeffrey

    2015-01-01

    Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in the male and female rat to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both the male and female rat indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contributes to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. PMID:26522833

  7. AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

    PubMed Central

    Whiting, Jennifer L.; Ogier, Leah; Forbush, Katherine A.; Bucko, Paula; Gopalan, Janani; Seternes, Ole-Morten; Langeberg, Lorene K.; Scott, John D.

    2016-01-01

    Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an “actin barrier” that obstructs the passive transit of AQP2 to the plasma membrane. Bidirectional control of AQP2 trafficking is managed by hormones and signaling enzymes. We have discovered that vasopressin-independent facets of this homeostatic mechanism are under the control of A-Kinase Anchoring Protein 220 (AKAP220; product of the Akap11 gene). CRISPR/Cas9 gene editing and imaging approaches show that loss of AKAP220 disrupts apical actin networks in organoid cultures. Similar defects are evident in tissue sections from AKAP220-KO mice. Biochemical analysis of AKAP220-null kidney extracts detected reduced levels of active RhoA GTPase, a well-known modulator of the actin cytoskeleton. Fluorescent imaging of kidney sections from these genetically modified mice revealed that RhoA and AQP2 accumulate at the apical surface of the collecting duct. Consequently, these animals are unable to appropriately dilute urine in response to overhydration. We propose that membrane-proximal signaling complexes constrained by AKAP220 impact the actin barrier dynamics and AQP2 trafficking to ensure water homeostasis. PMID:27402760

  8. Renal sodium reabsorption following induction of and recovery from volume expansion

    NASA Technical Reports Server (NTRS)

    Knight, T. F.; Weinman, E. J.

    1977-01-01

    In the rat, infusion of a volume of isotonic saline equal to 2% of body weight resulted in an 82% increase in the delivery of filtrate out of the proximal tubule but little or, in some animals, no change in the urinary excretion of sodium. By contrast, further degrees of volume expansion resulted in lesser increases in the distal delivery of filtrate, but were associated with a marked increase in the urinary excretion of sodium. Sixty minutes following completion of volume expansion, while the animals were still in positive sodium balance, the urinary excretion of sodium decreased 52% compared to a decrease of only 24% in the distal delivery of filtrate. During the course of progressive volume expansion and during the recovery phase, there was a dissociation between alterations in sodium reabsorption in the proximal convoluted tubule and in the whole kidney. These studies indicate that although the proximal tubule is more sensitive to changes in the extracellular fluid volume, distal nephron sites are ultimately responsible both for the natriuresis of volume expansion and the relative antinatriuresis of the recovery periods.

  9. Renal sodium reabsorption following induction of and recovery from volume expansion

    NASA Technical Reports Server (NTRS)

    Knight, T. F.; Weinman, E. J.

    1977-01-01

    In the rat, infusion of a volume of isotonic saline equal to 2% of body weight resulted in an 82% increase in the delivery of filtrate out of the proximal tubule but little or, in some animals, no change in the urinary excretion of sodium. By contrast, further degrees of volume expansion resulted in lesser increases in the distal delivery of filtrate, but were associated with a marked increase in the urinary excretion of sodium. Sixty minutes following completion of volume expansion, while the animals were still in positive sodium balance, the urinary excretion of sodium decreased 52% compared to a decrease of only 24% in the distal delivery of filtrate. During the course of progressive volume expansion and during the recovery phase, there was a dissociation between alterations in sodium reabsorption in the proximal convoluted tubule and in the whole kidney. These studies indicate that although the proximal tubule is more sensitive to changes in the extracellular fluid volume, distal nephron sites are ultimately responsible both for the natriuresis of volume expansion and the relative antinatriuresis of the recovery periods.

  10. Response of copper deficient rats to inhibitors of renal sodium reabsorption

    SciTech Connect

    Noordewier, B.; Saari, J.T. USDA/ARS, Grand Forks, ND )

    1991-03-11

    This study examined the effects of furosemide (Furo), a Loop diuretic, and amiloride (Am), a potassium (K)-sparing diuretic, on the excretion of sodium (Na) and K in copper-adequate (CuAdeq) and copper-deficient (CuDef) rats. Weanling male Sprague Dawley rats were fed a CuDef or CuAdeq diet ad libitum and given deionized water to drink. After 5 weeks on the diets, rats were assigned to one of four treatment regimens: Furo, Am or Furo + Am. Rats were anesthetized and electrolyte excretion was measured in 2 {times} 15 min control periods followed by 3 {times} 15 min treatment periods. Furo increased Na excretion in a dose dependent manner in both the CuAdeq and the CuDef rats. The response of the CuAdeq rats was slightly greater than that of the CuDef rats in each of the 3 treatment groups in which Furo was given. K excretion following Furo increased to the same extent in the CuAdeq and CuDef rats. The natriuretic response to Am alone was slightly greater in the CuDef than the CuAdeq rats. The antikaliuretic response of the CuDef rats was similar to that of the CuAdeq rats whether Am was given alone or in combination with Furo. These data show that CuDef rats respond to Furo and Am in a manner which is similar to that of CuAdeq rats, this indicates that the sensitivity of the Na reabsorption mechanisms to inhibition by diuretics is not markedly affected by copper deficiency.

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    1987-02-01

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

  13. Renal bicarbonate reabsorption in the rat. III. Distal tubule perfusion study of load dependence and bicarbonate permeability.

    PubMed Central

    Chan, Y L; Malnic, G; Giebisch, G

    1989-01-01

    Using continuous microperfusion techniques, we studied the load dependence of bicarbonate reabsorption along cortical distal tubules of the rat kidney and their bicarbonate permeability. Net bicarbonate transport was evaluated from changes in tracer inulin concentrations and total CO2 measurements by microcalorimetry. Bicarbonate permeability was estimated from the flux of total CO2 along known electrochemical gradients into bicarbonate-and chloride-free perfusion solution containing 10(-4) M acetazolamide. Transepithelial potential differences were measured with conventional glass microelectrodes. Significant net bicarbonate reabsorption occurred at luminal bicarbonate levels from 5 to 25 mM, and at perfusion rates from 5 to 30 nl/min. Bicarbonate reabsorption increased in a load-dependent manner, both during increments in luminal bicarbonate concentration or perfusion rate, reaching saturation at a load of 250 pmol/min with a maximal reabsorption rate of approximately 75 pmol/min.mm. Rate of bicarbonate reabsorption was flow dependent at luminal concentrations of 10 but not at 25 mM. During chronic metabolic alkalosis, maximal rates of reabsorption were significantly reduced to 33 pmol/min.mm. The bicarbonate permeability was 2.32 +/- 0.13 x 10(-5) cm/s in control rats, and 2.65 +/- 0.26 x 10(-5) cm/s in volume-expanded rats. Our data indicate that at physiological bicarbonate concentrations in the distal tubule passive bicarbonate fluxes account for only 16-21% of net fluxes. At high luminal bicarbonate concentrations, passive bicarbonate reabsorption contributes moderately to net reabsorption of this anion. PMID:2760220

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

    PubMed Central

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

    2014-01-01

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

  15. pH gradient as an additional driving force in the renal re-absorption of phosphate.

    PubMed Central

    Strévey, J; Giroux, S; Béliveau, R

    1990-01-01

    The effects of the Na+ gradient and pH on phosphate uptake were studied in brush-border membrane vesicles isolated from rat kidney cortex. The initial rates of Na(+)-dependent phosphate uptake were measured at pH 6.5, 7.5 and 8.5 in the presence of sodium gluconate. At a constant total phosphate concentration, the transport values at pH 7.5 and 8.5 were similar, but at pH 6.5 the influx was 31% of that at pH 7.5. However, when the concentration of bivalent phosphate was kept constant at all three pH values, the effect of pH was less pronounced; at pH 6.5, phosphate influx was 73% of that measured at pH 7.5. The Na(+)-dependent phosphate uptake was also influenced by a transmembrane pH difference; an outwardly directed H+ gradient stimulated the uptake by 48%, whereas an inwardly directed H+ gradient inhibited the uptake by 15%. Phosphate on the trans (intravesicular) side stimulated the Na(+)-gradient-dependent phosphate transport by 59%, 93% and 49%, and the Na(+)-gradient-independent phosphate transport by 240%, 280% and 244%, at pH 6.5, 7.5 and 8.5 respectively. However, in both cases, at pH 6.5 the maximal stimulation was seen only when the concentration of bivalent trans phosphate was the same as at pH 7.5. In the absence of a Na+ gradient, but in the presence of Na+, an outwardly directed H+ gradient provided the driving force for the transient hyperaccumulation of phosphate. The rate of uptake was dependent on the magnitude of the H+ gradient. These results indicate that: (1) the bivalent form of phosphate is the form of phosphate recognized by the carrier on both sides of the membrane; (2) protons are both activators and allosteric modulators of the phosphate carrier; (3) the combined action of both the Na+ (out/in) and H+ (in/out) gradients on the phosphate carrier contribute to regulate efficiently the re-absorption of phosphate. PMID:2244874

  16. FGF23 Is Not Associated With Age-Related Changes in Phosphate, but Enhances Renal Calcium Reabsorption in Girls.

    PubMed

    Mitchell, Deborah M; Jüppner, Harald; Burnett-Bowie, Sherri-Ann M

    2017-04-01

    Fibroblast growth factor (FGF)23 is a critical determinant of phosphate homeostasis. The role of FGF23, however, in regulating physiologic changes in serum phosphate and renal phosphate handling across childhood is not well described. In addition, animal models have suggested a role for FGF23 in regulating renal calcium excretion. To assess changes in FGF23 concentrations across childhood in relation to changes in mineral ions and hormones of mineral ion homeostasis. This was a cross-sectional study. The study was conducted at a Clinical Research Center at a tertiary care hospital. Ninety healthy girls ages 9 to 18 years were recruited from the surrounding community. The associations of intact and C-terminal FGF23 concentrations with measures of mineral ion homeostasis were determined by univariable and multivariable linear regression. Serum phosphate and renal phosphate excretion varied with age, as expected (R = -0.49, P < 0.001 and R = -0.48, P < 0.001, respectively). Neither intact nor C-terminal FGF23 varied with age, and FGF23 was not correlated with serum or urinary phosphate. Intact FGF23 was positively correlated with serum calcium (R = 0.39, P < 0.001) and negatively correlated with urinary calcium/creatinine ratio (R = -0.27, P = 0.011). The changes in serum and urinary phosphate handling across childhood do not appear to be determined by alterations in FGF23 concentrations. These data may point to a role for FGF23 in calcium regulation in human physiology.

  17. Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium.

    PubMed

    Hou, Jianghui; Renigunta, Aparna; Gomes, Antonio S; Hou, Mingli; Paul, David L; Waldegger, Siegfried; Goodenough, Daniel A

    2009-09-08

    Claudins are tight junction integral membrane proteins that are key regulators of the paracellular pathway. Defects in claudin-16 (CLDN16) and CLDN19 function result in the inherited human renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Previous studies showed that siRNA knockdown of CLDN16 in mice results in a mouse model for FHHNC. Here, we show that CLDN19-siRNA mice also developed the FHHNC symptoms of chronic renal wasting of magnesium and calcium together with defective renal salt handling. siRNA knockdown of CLDN19 caused a loss of CLDN16 from tight junctions in the thick ascending limb (TAL) without a decrease in CLDN16 expression level, whereas siRNA knockdown of CLDN16 produced a similar effect on CLDN19. In both mouse lines, CLDN10, CLDN18, occludin, and ZO-1, normal constituents of TAL tight junctions, remained correctly localized. CLDN16- and CLDN19-depleted tight junctions had normal barrier function but defective ion selectivity. These data, together with yeast two-hybrid binding studies, indicate that a heteromeric CLDN16 and CLDN19 interaction was required for assembling them into the tight junction structure and generating cation-selective paracellular channels.

  18. High serum levels of soluble Fas (sFas) in CKD patients: effects of renal clearance, reabsorption and synthesis.

    PubMed

    Dalboni, M A; Cenedeze, M A; Manfredi, S R; Cruz Andreoli, M C; Pavao Dos Santos, O; Canziani, M E; Boim, M A; Goes, M A; Draibe, S A; Balakrishnan, V; Cendoroglo, M

    2008-05-01

    Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD. We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.

  19. Selective SGLT2 inhibition by tofogliflozin reduces renal glucose reabsorption under hyperglycemic but not under hypo- or euglycemic conditions in rats.

    PubMed

    Nagata, Takumi; Fukazawa, Masanori; Honda, Kiyofumi; Yata, Tatsuo; Kawai, Mio; Yamane, Mizuki; Murao, Naoaki; Yamaguchi, Koji; Kato, Motohiro; Mitsui, Tetsuya; Suzuki, Yoshiyuki; Ikeda, Sachiya; Kawabe, Yoshiki

    2013-02-15

    To understand the risk of hypoglycemia associated with urinary glucose excretion (UGE) induced by sodium-glucose cotransporter (SGLT) inhibitors, it is necessary to know the relationship between the ratio of contribution of SGLT2 vs. SGLT1 to renal glucose reabsorption (RGR) and the glycemic levels in vivo. To examine the contributions of SGLT2 and SGLT1 in normal rats, we compared the RGR inhibition by tofogliflozin, a highly specific SGLT2 inhibitor, and phlorizin, an SGLT1 and SGLT2 (SGLT1/2) inhibitor, at plasma concentrations sufficient to completely inhibit rat SGLT2 (rSGLT2) while inhibiting rSGLT1 to different degrees. Under hyperglycemic conditions by glucose titration, tofogliflozin and phlorizin achieved ≥50% inhibition of RGR. Under hypoglycemic conditions by hyperinsulinemic clamp, RGR was reduced by 20-50% with phlorizin and by 1-5% with tofogliflozin, suggesting the smaller contribution of rSGLT2 to RGR under hypoglycemic conditions than under hyperglycemic conditions. Next, to evaluate the hypoglycemic potentials of SGLT1/2 inhibition, we measured the plasma glucose (PG) and endogenous glucose production (EGP) simultaneously after UGE induction by SGLT inhibitors. Tofogliflozin (400 ng/ml) induced UGE of about 2 mg·kg⁻¹·min⁻¹ and increased EGP by 1-2 mg·kg⁻¹·min⁻¹, resulting in PG in the normal range. Phlorizin (1,333 ng/ml) induced UGE of about 6 mg·kg⁻¹·min⁻¹ and increased EGP by about 4 mg·kg⁻¹·min⁻¹; this was more than with tofogliflozin, but the minimum PG was lower. These results suggest that the contribution of SGLT1 to RGR is greater under lower glycemic conditions than under hyperglycemic conditions and that SGLT2-selective inhibitors pose a lower risk of hypoglycemia than SGLT1/2 inhibitors.

  20. TRPV5-mediated Ca2+ Reabsorption and Hypercalciuria

    NASA Astrophysics Data System (ADS)

    Renkema, Kirsten Y.; Hoenderop, Joost G. J.; Bindels, René J. M.

    2007-04-01

    The concerted action of the intestine, kidney and bone results in the maintenance of a normal Ca2+ balance, a mechanism that is tightly controlled by the calciotropic hormones vitamin D, parathyroid hormone and calcitonin. Disturbances in the Ca2+ balance have been linked to diverse pathophysiological disorders like urolithiasis, hypertension, electroencephalogram abnormalities and rickets. Importantly, the final amount of Ca2+ that is released from the body is determined in the distal part of the nephron, where active Ca2+ reabsorption occurs. Here, Transient Receptor Potential Vanilloid member 5 (TRPV5), a highly Ca2+-selective channel, has been recognized as the gatekeeper of active Ca2+ reabsorption. The in vivo relevance of TRPV5 has been further investigated by the characterization of TRPV5 knockout (TRPV5-/-) mice, which exhibit severe disturbances in renal Ca2+ handling, such as profound hypercalciuria, intestinal Ca2+ hyperabsorption and reduced bone thickness. Hypercalciuria increases the risk of kidney stone formation in these mice. This review highlights our current knowledge about TRPV5-mediated Ca2+ reabsorption and emphasizes the physiological relevance and the clinical implications related to the TRPV5-/- mice model.

  1. Genetic link between renal birth defects and congenital heart disease

    PubMed Central

    San Agustin, Jovenal T.; Klena, Nikolai; Granath, Kristi; Panigrahy, Ashok; Stewart, Eileen; Devine, William; Strittmatter, Lara; Jonassen, Julie A.; Liu, Xiaoqin; Lo, Cecilia W.; Pazour, Gregory J.

    2016-01-01

    Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD. PMID:27002738

  2. Genetic link between renal birth defects and congenital heart disease.

    PubMed

    San Agustin, Jovenal T; Klena, Nikolai; Granath, Kristi; Panigrahy, Ashok; Stewart, Eileen; Devine, William; Strittmatter, Lara; Jonassen, Julie A; Liu, Xiaoqin; Lo, Cecilia W; Pazour, Gregory J

    2016-03-22

    Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD.

  3. Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

    PubMed Central

    2011-01-01

    Background Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies. Methods Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test. Results Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013). Conclusions PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity. PMID

  4. Renal Response to L-Arginine in Diabetic Rats. A Possible Link between Nitric Oxide System and Aquaporin-2

    PubMed Central

    Ortiz, María C.; Albertoni Borghese, María F.; Balonga, Sabrina E.; Lavagna, Agustina; Filipuzzi, Ana L.; Elesgaray, Rosana; Costa, María A.; Majowicz, Mónica P.

    2014-01-01

    The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression. PMID:25111608

  5. Inhibition of sodium-linked glucose reabsorption normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A₁-receptor deficient mice.

    PubMed

    Sällström, J; Eriksson, T; Fredholm, B B; Persson, A E G; Palm, F

    2014-02-01

    Glomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. Sustained hyperglycaemia is also closely associated with kidney hypertrophy and increased electrolyte and glucose reabsorption in the proximal tubule. In this study, we investigated the role of the increased tubular sodium/glucose cotransport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback (TGF) mechanism, we used adenosine A₁-receptor deficient (A1AR(-/-)) mice known to lack a functional TGF mechanism and compared the results to corresponding wild-type animals (A1AR(+/+)). Diabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose cotransporters were inhibited by phlorizin 30 min prior to GFR measurements. Normoglycaemic animals had a similar GFR independent of genotype (A₁AR(+/+) 233 ± 11 vs. A₁AR(-/-) 241 ± 25 μL min(-1)), and induction of diabetes resulted in glomerular hyperfiltration in both groups (A₁AR(+/+) 380 ± 25 vs. A₁AR(-/-) 336 ± 35 μL min(-1); both P < 0.05). Phlorizin had no effect on GFR in normoglycaemic mice, whereas it reduced GFR in both genotypes during diabetes (A₁AR(+/+) 365 ± 18 to 295 ± 19, A₁AR(-/-) 354 ± 38 to 199 ± 15 μL min(-1); both P < 0.05). Notably, the reduction was more pronounced in the A₁AR(-/-) (P < 0.05). This study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Primary cultures of renal epithelial cells from X-linked hypophosphatemic (Hyp) mice express defects in phosphate transport and vitamin D metabolism.

    PubMed Central

    Bell, C L; Tenenhouse, H S; Scriver, C R

    1988-01-01

    Mutation in a gene (symbol Hyp) on the X chromosome causes hypophosphatemia in the mouse. The murine phenotype is a counterpart of X-linked hypophosphatemia in man. Both exhibit impaired renal reabsorption of phosphate in vivo. In vitro studies in the Hyp mouse have shown decreased Na+-dependent phosphate transport at the brush border membrane and abnormal mitochondrial vitamin D metabolism. To determine whether the mutant renal phenotype is intrinsic to the kidney or dependent upon putative extrinsic humoral factor(s) for its expression, we established primary cultures of renal epithelial cells from normal and Hyp male mouse kidneys. The cells are derived from proximal tubule. Initial uptake rates of phosphate and alpha-methyl-D-glucopyranoside (alpha-MG), a metabolically inert analogue of D-glucose, were measured simultaneously in confluent monolayers exhibiting epithelial polarity and tight junctions. The mean phosphate/alpha-MG uptake ratio in Hyp cultures was 82% of that in normal cells (P less than 0.01, n = 96). Moreover, the production of 24,25-dihydroxyvitamin D3 was significantly elevated in confluent cultures of Hyp cells relative to normal cells. These results imply that the Hyp gene is expressed in situ in renal epithelium and suggest that humoral factors are not necessary for the mutant renal phenotype in X-linked hypophosphatemia of mouse and man. PMID:3414685

  7. Role of distal reabsorption and peritubular environment in glomerulotubular balance.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.

    1972-01-01

    Total kidney glomerulotubular balance was examined during aortic constriction and release in saline-loaded dogs and in dogs undergoing water diuresis. Aortic constriction lowered the glomerular filtration rate by 45% in both groups, and glomerulotubular balance, as judged by changes in absolute sodium reabsorption, was also comparable. During water diuresis, a linear relationship was observed between free water clearance and urine flow during all maneuvers, suggesting that distal sodium reabsorption is related primarily to distal delivery. The results suggest that if alterations in the peritubular environment are responsible for the changes in tubular sodium reabsorption during aortic constriction in the saline- or water-loaded dog, then a change in renal plasma flow, and presumably delivery rate of oncotic force, may be the most likely mediator.

  8. Evidence for bicarbonate-dependent magnesium reabsorption.

    PubMed

    Hartmann, A; Langberg, H; Dibona, G; Kiil, F

    1983-01-01

    During ethacrynic acid administration about 50% of the filtered load of magnesium is reabsorbed. To examine whether the remaining component of magnesium reabsorption is bicarbonate-dependent, i.e. varies with factors known to alter passive reabsorption, experiments were performed in anesthetized dogs. During ethacrynic acid administration MgCl2 infusion raised the plasma concentration of magnesium (PMg) from 0.64 +/- 0.05 to 3.06 +/- 0.27 mM and doubled magnesium reabsorption. The infusion of acetazolamide at high PMg reduced bicarbonate reabsorption by 41 +/- 3% and magnesium reabsorption by 31 +/- 16%. When plasma pH was reduced to 7.04 +/- 0.02 and increased to 7.83 +/- 0.02 by altering PCO2 at a constant plasma bicarbonate concentration of 31.2 +/- 0.8 mM, magnesium and bicarbonate reabsorption were correlated (r = 0.82). The infusion of mannitol, which acts by reducing passive solute transport without affecting bicarbonate reabsorption, halved magnesium reabsorption. By combining mannitol and acetazolamide infusions, only 6 +/- 4% of the filtered magnesium was still reabsorbed. These results indicate that the reabsorption of magnesium remaining after the infusion of ethacrynic acid and after raising PMg varies with changes in PCO2 and is inhibited by the infusion of acetazolamide and mannitol as expected for bicarbonate-dependent passive reabsorption.

  9. Cubilin and amnionless mediate protein reabsorption in Drosophila nephrocytes.

    PubMed

    Zhang, Fujian; Zhao, Ying; Chao, Yufang; Muir, Katherine; Han, Zhe

    2013-02-01

    The insect nephrocyte and the mammalian glomerular podocyte are similar with regard to filtration, but it remains unclear whether there is an organ or cell type in flies that reabsorbs proteins. Here, we show that the Drosophila nephrocyte has molecular, structural, and functional similarities to the renal proximal tubule cell. We screened for genes required for nephrocyte function and identified two Drosophila genes encoding orthologs of mammalian cubilin and amnionless (AMN), two major receptors for protein reabsorption in the proximal tubule. In Drosophila, expression of dCubilin and dAMN is specific to nephrocytes, where they function as co-receptors for protein uptake. Targeted expression of human AMN in Drosophila nephrocytes was sufficient to rescue defective protein uptake induced by dAMN knockdown, suggesting evolutionary conservation of Cubilin/AMN co-receptors function from flies to humans. Furthermore, we found that Cubilin/AMN-mediated protein reabsorption is required for the maintenance of nephrocyte ultrastructure and fly survival under conditions of toxic stress. In conclusion, the insect nephrocyte combines filtration with protein reabsorption, using evolutionarily conserved genes and subcellular structures, suggesting that it can serve as a simplified model for both podocytes and the renal proximal tubule.

  10. SGLT2 mediates glucose reabsorption in the early proximal tubule.

    PubMed

    Vallon, Volker; Platt, Kenneth A; Cunard, Robyn; Schroth, Jana; Whaley, Jean; Thomson, Scott C; Koepsell, Hermann; Rieg, Timo

    2011-01-01

    Mutations in the gene encoding for the Na(+)-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood. Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterized SGLT2-deficient mice. In wild-type (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal tubule. Sglt2(-/-) mice had glucosuria, polyuria, and increased food and fluid intake without differences in plasma glucose concentrations, GFR, or urinary excretion of other proximal tubular substrates (including amino acids) compared with WT mice. SGLT2 deficiency did not associate with volume depletion, suggested by similar body weight, BP, and hematocrit; however, plasma renin concentrations were modestly higher and plasma aldosterone levels were lower in Sglt2(-/-) mice. Whole-kidney clearance studies showed that fractional glucose reabsorption was significantly lower in Sglt2(-/-) mice compared with WT mice and varied in Sglt2(-/-) mice between 10 and 60%, inversely with the amount of filtered glucose. Free-flow micropuncture revealed that for early proximal collections, 78 ± 6% of the filtered glucose was reabsorbed in WT mice compared with no reabsorption in Sglt2(-/-) mice. For late proximal collections, fractional glucose reabsorption was 93 ± 1% in WT and 21 ± 6% in Sglt2(-/-) mice, respectively. These results demonstrate that SGLT2 mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. This mouse model mimics and explains the glucosuric phenotype of individuals carrying SLC5A2 mutations.

  11. Bicarbonate reabsorption by the kidney of the newborn rabbit.

    PubMed

    van der Heijden, A J; Guignard, J P

    1989-01-01

    Bicarbonate reabsorption by the immature kidney in response to acute acid-base changes was assessed in 50 anesthetized newborn rabbits before the end of nephrogenesis. The normal newborn rabbit (age 5-12 days) is in a state of hypochloremic metabolic alkalosis (PHCO3-, 31.9 +/- 0.6 mmol/l; PCl-, 83.1 +/- 1.0) and excretes a hypertonic (Uosmol = 578 +/- 41 mosmol/kgH2O), alkaline (UpH = 7.40 +/- 0.15) urine containing 50 +/- 9 mmol/l Cl- and 13 +/- 4 mmol/l Na+. The alkalosis is probably generated by an alkaline load contained in the mother's milk and maintained by a state of chloride wasting and volume contraction. In this alkalotic model, bicarbonate reabsorption, expressed per milliliter glomerular filtration rate (GFR), correlates positively with arterial CO2 pressure (PaCO2). The ability of the immature kidney to reclaim filtered bicarbonate in response to an elevation of the plasma carbon dioxide tension remains unlimited up to PaCO2 of 110 mmHg (y = 20.7 + 0.15 x, r = 0.82, P less than 0.001). Hypercapnia is associated with a marked fall in GFR, so that the positive correlation between bicarbonate reabsorption and PaCO2 vanishes when the bicarbonate reabsorption rate is expressed in absolute terms. Bicarbonate reabsorption is strongly dependent on the filtered load during both acutely induced metabolic acidosis and alkalosis. The acid-base state of the newborn rabbit is in sharp contrast with that of most animal species, and the renal handling of bicarbonate as a function of GFR does not show signs of tubular immaturity.

  12. Tubular maximum phosphate reabsorption capacity in living kidney donors is independently associated with one year recipient GFR.

    PubMed

    van Londen, Marco; Aarts, Brigitte M; Sanders, Jan-Stephan F; Hillebrands, Jan-Luuk; Bakker, Stephan J L; Navis, Gerjan; de Borst, Martin H

    2017-10-04

    The donor glomerular filtration rate (GFR) measured before kidney donation is a strong determinant of recipient graft outcome. No tubular function markers have been identified that can similarly be used in donors to predict recipient outcomes. In the current study we investigated whether the predonation tubular maximum reabsorption capacity of phosphate (TmP-GFR), which may be considered as a functional tubular marker in healthy kidney donors, is associated with recipient GFR at one year after transplantation, a key determinant of long-term outcome. We calculated the predonation TmP-GFR from serum and 24h-urine phosphate and creatinine levels in 165 kidney donors, and recipient 125I-iothalamate GFR and eGFR (CKD-EPI) at 12 months after transplantation. Kidney donors were 51±10 years old, 47% were men, and mean GFR was 118±26 mL/min. The donor TmP-GFR was associated with recipient GFR 12 months after transplantation (GFR 6.0 mL/min lower per 1 mg/dL decrement of TmP-GFR), which persisted after multivariable adjustment for donor age, sex, predonation GFR and blood pressure and other potential confounders. Results were highly similar when eGFR at 12 months was taken as the outcome. Tubular damage markers KIM-1 and NGAL were low and not associated with recipient GFR. A lower donor TmP-GFR before donation, which may be considered to represent a functional measure of tubular phosphate reabsorption capacity, is independently associated with a lower recipient GFR one year after transplantation. These data are the first to link donor tubular phosphate reabsorption with recipient GFR post-transplantation. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  13. Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35

    SciTech Connect

    Kos, C.H.; Tenenhouse, H.S. ); Tihy, F.; Lemieux, N. ); Econs, M.J. ); Murer, H. )

    1994-01-01

    Several Mendelian disorders of renal phosphate reabsorption, associated with hypophosphatemia and bone disease, have been described. These include X-linked hypophosphatemia (XLH), hereditary hypophosphatemic rickets with hypercalciuria, hypophosphatemic bone disease, and autosomal dominant and autosomal recessive hypophosphatemic rickets. The underlying mechanisms for renal phosphate wasting in these disorders remain unknown. The proximal tubule is the major site of renal phosphate reabsorption. Thus, mutations in genes that participate in the transepithelial transport of phosphate in this segment of the nephron may be responsible for these disorders. Recently, a cDNA encoding a renal proximal tubular, brush-border membrane Na[sup +]-phosphate cotransporter (NaP[sub i]-3) was cloned from human kidney cortex. As a first step in establishing whether mutations in the NaP[sub i]-3 gene are the cause of inherited disorders in phosphate homeostasis, the authors sought to determine its chromosomal localization. 9 refs., 1 fig.

  14. Effects of photon reabsorption phenomena in confocal micro-photoluminescence measurements in crystalline silicon

    NASA Astrophysics Data System (ADS)

    Roigé, A.; Alvarez, J.; Jaffré, A.; Desrues, T.; Muñoz, D.; Martín, I.; Alcubilla, R.; Kleider, J.-P.

    2017-02-01

    Confocal micro-photoluminescence (PL) spectroscopy has become a powerful characterization technique for studying novel photovoltaic (PV) materials and structures at the micrometer level. In this work, we present a comprehensive study about the effects and implications of photon reabsorption phenomena on confocal micro-PL measurements in crystalline silicon (c-Si), the workhorse material of the PV industry. First, supported by theoretical calculations, we show that the level of reabsorption is intrinsically linked to the selected experimental parameters, i.e., focusing lens, pinhole aperture, and excitation wavelength, as they define the spatial extension of the confocal detection volume, and therefore, the effective photon traveling distance before collection. Second, we also show that certain sample properties such as the reflectance and/or the surface recombination velocity can also have a relevant impact on reabsorption. Due to the direct relationship between the reabsorption level and the spectral line shape of the resulting PL emission signal, reabsorption phenomena play a paramount role in certain types of micro-PL measurements. This is demonstrated by means of two practical and current examples studied using confocal PL, namely, the estimation of doping densities in c-Si and the study of back-surface and/or back-contacted Si devices such as interdigitated back contact solar cells, where reabsorption processes should be taken into account for the proper interpretation and quantification of the obtained PL data.

  15. Augmented bicarbonate reabsorption by both the proximal and distal nephron maintains chloride-deplete metabolic alkalosis in rats.

    PubMed Central

    Wesson, D E

    1989-01-01

    Whether augmented bicarbonate reabsorption by renal tubular epithelium contributes to the maintenance of chloride-deplete metabolic alkalosis is not clear. This study used free-flow micropuncture to investigate bicarbonate reabsorption by surface nephron segments in a rat model of diuretic-induced alkalosis compared to control. The proximal and distal nephron of the alkalotic animals had higher values for both delivered load to and absolute reabsorption from these segments. The proximal tubules of alkalotic and control animals had similar values for the slopes of the linear regression of delivered load vs. reabsorption and for the bicarbonate tubular fluid to plasma (TF/P) ratio at the late proximal tubule. By contrast, the corresponding analysis for the distal segment of alkalotic animals revealed a greater slope (0.98 vs. 0.81, P less than 0.003) and a smaller bicarbonate TF/P ratio at the late distal tubule (0.10 vs. 0.16, P less than 0.006). The data indicate that augmented bicarbonate reabsorption by both the proximal and distal nephron contributes to maintaining the alkalosis of this model. The data suggest primary stimulation of bicarbonate reabsorption in the distal nephron and load-dependent reabsorption in the proximal tubule. PMID:2808701

  16. Nonlinear kinetics of the thiamine cation in humans: saturation of nonrenal clearance and tubular reabsorption.

    PubMed

    Weber, W; Nitz, M; Looby, M

    1990-12-01

    The pharmacokinetics of thiamine in plasma and urine was investigated in 13 healthy and 3 renal-insufficient volunteers. Doses ranging from 5 to 200 mg thiamine hydrochloride were administered either as an iv bolus or a 50-min infusion. A sum of 3 exponentials was used as the unit impulse response function to characterize plasma kinetics. Drug input was mathematically described as a rectangular pulse of length 2 or 50 min. Total clearance, defined as the reciprocal of the area under the unit impulse response function, was found to depend on dose and creatinine clearance, as shown by a multiple nonlinear regression analysis. The nonrenal component of the total clearance was demonstrated to be dose-dependent, whereas its mean renal component was only dependent on creatinine clearance. At high plasma concentrations renal clearance approached renal plasma flow, and remained constant during the decline to near physiological plasma levels. With further decline under a characteristic threshold concentration, renal clearance decreased far below the glomerular filtration rate, indicating tubular reabsorption. Binding to plasma proteins was excluded by ultrafiltration experiments. The process of renal excretion can be described by a combination of glomerular filtration, flow-dependent tubular secretion, and saturable tubular reabsorption. The concentration dependency of renal clearance was reflected in its mean value, which was only 76% of its maximum value measured in the higher concentration range. In the dose range studied, most of the given dose had already been linearly excreted before tubular reabsorption became evident, and consequently the measured mean renal clearances did not differ enough from one another to exhibit the expected dose dependency. With increasing dose a shift of the cleared dose fraction from the nonrenal to the renal side was observed. Saturated nonrenal clearance alone could explain this effect.

  17. Renal amyloidosis in a patient with X-linked agammaglobulinemia (Bruton's disease) and bronchiectasis.

    PubMed

    Gonzalo-Garijo, M A; Sánchez-Vega, S; Pérez-Calderón, R; Pérez-Rangel, I; Corrales-Vargas, S; Fernández de Mera, J J; Robles, R

    2014-01-01

    We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis. A 38 year-old man was diagnosed with X-linked agammaglobulinemia (Bruton's disease) when he was 3 years old, and he has been treated with parenteral immunoglobulin since then. Eighteen years later, he was diagnosed with central pulmonary bronchiectasis by computerized tomography (CT). In 2008, he gradually developed anemia, edema of lower limbs, and loss of weight. Laboratory studies revealed deterioration of renal function, normocytic normochromic anemia and nephrotic range proteinuria. Hepatitis B and C and HIV serology were negative. Ultrasound and CT of abdomen were normal. A renal biopsy revealed deposits with positive PAS and Congo red staining in glomeruli, interstitium, and vessel's walls. Immunohistochemistry showed positive staining of the A amyloid. Direct immunofluorescence was positive with thioflavin and showed focal and glomerular mesangial IgG deposits, suggesting renal AA amyloidosis. For 2 years the patient conducted pharmacological treatment and follow-up for the Nephrology department with poor prognosis and progression of renal function impairment. In January 2011 he began dialysis treatment with improvement, and he is currently on the waiting list for renal transplantation. We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis a finding rarely reported.

  18. Special focus on the role of α(1D)-adrenoreceptors in the assessment of renal tubular sodium re-absorptive responses in spontaneously hypertensive rats subjected to high sodium diet.

    PubMed

    Kazi, Raisa N; Sattar, Munavvar A; Abdullah, Nor A; Khan, Md A Hye; Rathore, Hassaan A; Abdulla, Mohammed H; Salman, Ibrahim M; Johns, Edward J

    2011-03-01

    α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(₁D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α₁-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(₁D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.

  19. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  20. Isosmotic volume reabsorption in rat proximal tubule

    PubMed Central

    1980-01-01

    A theoretical model incorporation both active and passive forces has been developed for fluid reabsorption from split oil droplets in rat intermediate and late proximal tubule. Of necessity, simplifying assumptions have been introduced; we have assumed that the epithelium can be treated as a single membrane and that the membrane "effective" HCO3 permeability is near zero. Based on this model with its underlying assumptions, the following conclusions are drawn. Regardless of the presence or absence of active NaCl transport, fluid reabsorption from the split oil droplet is isosmotic. The reabsorbate osmolarity can be affected by changes in tubular permeability parameters and applied forces but is not readily altered from an osmolarity essentially equal to that of plasma. In a split droplet, isosmotic flow need not be a special consequence of active Na transport, is not the result of a particular set of permeability properties, and is not merely a trivial consequence of a very high hydraulic conductivity; isosmotic flow can be obtained with hydraulic conductivity nearly an order of magnitude lower than that previously measured in the rat proximal convoluted tubule. Isosmotic reabsorption is, in part, the result of the interdependence of salt and water flows, their changing in parallel, and thus their ratio, the reabsorbate concentration being relatively invariant. Active NaCl transport can cause osmotic water flow by reducing the luminal fluid osmolarity. In the presence of passive forces the luminal fluid can be hypertonic to plasma, and active NaCl transport can still exert its osmotic effect on volume flow. There are two passive forces for volume flow: the Cl gradient and the difference in effective osmotic pressure; they have an approximately equivalent effect on volume flow. Experimentally, we have measured volume changes in a droplet made hyperosmotic by the addition of 50 mM NaCl; the experimental results are predicted reasonably well by our theoretical model

  1. Isosmotic volume reabsorption in rat proximal tubule.

    PubMed

    Warner, R R; Lechene, C

    1980-11-01

    A theoretical model incorporation both active and passive forces has been developed for fluid reabsorption from split oil droplets in rat intermediate and late proximal tubule. Of necessity, simplifying assumptions have been introduced; we have assumed that the epithelium can be treated as a single membrane and that the membrane "effective" HCO3 permeability is near zero. Based on this model with its underlying assumptions, the following conclusions are drawn. Regardless of the presence or absence of active NaCl transport, fluid reabsorption from the split oil droplet is isosmotic. The reabsorbate osmolarity can be affected by changes in tubular permeability parameters and applied forces but is not readily altered from an osmolarity essentially equal to that of plasma. In a split droplet, isosmotic flow need not be a special consequence of active Na transport, is not the result of a particular set of permeability properties, and is not merely a trivial consequence of a very high hydraulic conductivity; isosmotic flow can be obtained with hydraulic conductivity nearly an order of magnitude lower than that previously measured in the rat proximal convoluted tubule. Isosmotic reabsorption is, in part, the result of the interdependence of salt and water flows, their changing in parallel, and thus their ratio, the reabsorbate concentration being relatively invariant. Active NaCl transport can cause osmotic water flow by reducing the luminal fluid osmolarity. In the presence of passive forces the luminal fluid can be hypertonic to plasma, and active NaCl transport can still exert its osmotic effect on volume flow. There are two passive forces for volume flow: the Cl gradient and the difference in effective osmotic pressure; they have an approximately equivalent effect on volume flow. Experimentally, we have measured volume changes in a droplet made hyperosmotic by the addition of 50 mM NaCl; the experimental results are predicted reasonably well by our theoretical model.

  2. Relationship between tubular net sodium reabsorption and peritubular potassium uptake in the perfused Necturus kidney

    PubMed Central

    Giebisch, G.; Sullivan, L. P.; Whittembury, G.

    1973-01-01

    1. K influx from peritubular space into renal tubular cells, ϕiK, was measured in doubly perfused Necturus kidneys by studying tissue uptake of 42K added exclusively to the portal circulation. Concomitantly, net tubular Na reabsorption, ϕnNa, was measured by clearance techniques. ϕnNa and ϕiK were varied widely by replacing solutions of physiological composition (controls) with solutions containing high K, low K, low Na, cyclamate instead of Cl, ouabain (10-7-10-4 M) or ethacrynic acid (10-5-10-4 M). 2. The ratio of ϕnNa to ϕiK was found to vary with the experimental conditions, the control value of about 2 was maintained over a threefold variation in absolute Na reabsorption. This ratio increased with low K or ouabain to values near 4. With high K, ethacrynic acid, low Na or cyclamate the relationship was one or lower. Thus, net Na reabsorption can be uncoupled from peritubular K influx. 3. These results can be best explained if there are two Na pumps working in parallel: pump A transporting Na (with Cl) and pump B, a Na-for-K-exchange pump. The ratio of Na efflux to K influx could approach ∞ if only pump A works (if B is inhibited) and could approach one if only B works. It should vary between these limits in controls when both pumps are active, or when neither of the two pumps is completely inhibited. 4. Alternatively, the experimental findings could be explained by a Na pump with a coupling ratio that varies within two extreme values, from high Na-K ratios (with Na reabsorption at, or near, control values but with very low K influx values) to low ratios (with normal K influx values but with low Na reabsorption values). PMID:4702444

  3. Amiloride-sensitive sodium channel is linked to the cytoskeleton in renal epithelial cells

    SciTech Connect

    Smith, P.R.; Saccomani, G.; Benos, D.J. ); Eun-Hye, J.; Angelides, K.J. )

    1991-08-15

    Amiloride-sensitive sodium channels are localized to the microvillar domain of apical membranes in sodium-transporting renal epithelial cells. To elucidate the elements that maintain sodium channel distribution at the apical membrane, the authors searched for specific proteins associating with the channel. Triton X-100 extraction of A6 epithelial cells reveals that sodium channels are associated with detergent-insoluble and assembled cytoskeleton. Indirect immunofluorescence and confocal microscopy show that sodium channels are segregated to the apical microvillar membrane and colocalize with ankyrin, fodrin, and actin. They document by immunoblot analysis that ankyrin and fodrin remain associated with sodium channels after isolation and purification form bovine renal papillae. {sup 125}I-labeled ankyrin can be precipitated by anti-sodium-channel antibodies only in the presence of purified bovine sodium-channel complex. Direct binding of {sup 125}I-labeled ankyrin shows ankyrin binds to the 150-kDa sub-unit of the channel. Fluorescence photobleach lateral-diffusion measurements indicate sodium channels are severely restricted in their lateral mobility. They conclude that ankyrin links the amiloride-sensitive sodium channel to the underlying cytoskeleton and this association may sequester sodium channels at apical microvilli and maintain their polarized distribution in renal epithelial cells.

  4. Factors affecting proximal tubular reabsorption during development

    SciTech Connect

    Kaskel, F.J.; Kumar, A.M.; Lockhart, E.A.; Evan, A.; Spitzer, A.

    1987-01-01

    Studies performed in several animal species have demonstrated that glomerulotubular balance is maintained throughout development despite the many changes that occur in the factors known to control it. In an attempt to understand the nature of this phenomenon the authors quantified the magnitude and described the profile of these changes in guinea pigs. The changes in physical forces were assessed from measurements of hydrostatic and oncotic pressures, whereas those in the permeability characteristics of the proximal tubule epithelium were estimated from permanence to radioactivity-labelled macromolecules of graded radii, histologic measurements of the intercellular channels, and measurements of end-proximal ratio of tubular fluid-to-plasma osmolality (TF/P/sub osm/). Between 1 and 50 days of age the net pressure for reabsorption increased from 15.0 to 30.9 mmHg with the major change occurring during the first 2-3 wk of postnatal life. The urinary recovery of (/sup 3/H)inulin, (/sup 14/C)sucrose, and (/sup 14/C)creatinine, injected in the early segment of proximal tubules did not vary with age. The urinary recovery of (/sup 14/C)mannitol increased from 92% at birth to 100% at 49 days of age. The length of the zonulae occludens and the width of the intercellular channels did not change during this period. The findings support the hypothesis that during early postnatal life glomerulotubular balance is made possible by a high permeability of the proximal tubule, which compensates for the low net reabsorptive pressure. As the animal matures and the proximal tubule epithelium becomes tighter, for glomerulotubular balance to be maintained, an increase in the number of intercellular channels and in the active transport of sodium need to be postulated.

  5. Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis.

    PubMed

    Hunter, Robert W; Craigie, Eilidh; Homer, Natalie Z M; Mullins, John J; Bailey, Matthew A

    2014-02-15

    Na(+) reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K(+) excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K(+) balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na(+) channel (ENaC) downstream. This effect might be mediated by changes in distal Na(+) delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na(+) flux through ENaC, with a concomitant increase in renal K(+) excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K(+) excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na(+) reabsorption was not normally limited by Na(+) delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na(+) restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na(+) reabsorption through ENaC solely by increasing distal Na(+) delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.

  6. Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis

    PubMed Central

    Craigie, Eilidh; Homer, Natalie Z. M.; Mullins, John J.; Bailey, Matthew A.

    2014-01-01

    Na+ reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K+ excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K+ balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na+ channel (ENaC) downstream. This effect might be mediated by changes in distal Na+ delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na+ flux through ENaC, with a concomitant increase in renal K+ excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K+ excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na+ reabsorption was not normally limited by Na+ delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na+ restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na+ reabsorption through ENaC solely by increasing distal Na+ delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments. PMID:24402096

  7. Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia.

    PubMed

    Friedberg, C E; van Buren, M; Bijlsma, J A; Koomans, H A

    1991-08-01

    To examine the mechanism of renal sodium (Na) and potassium (K) retention during insulin infusion, seven healthy volunteers underwent clearance studies without (time control) and with insulin infusion (40 mU bolus, followed by 1 mU/kg/min for 150 min). Maximal free water clearance and fractional lithium clearance (FELi) were used to analyze renal sodium handling. Insulin decreased Na excretion (from 189 +/- 25 to 121 +/- 19 mumol/min, P less than 0.01) and K excretion (from 64 +/- 8 to 19 +/- 1 mumol/min, P less than 0.01), but did not change in glomerular filtration rate. FELi increased from 29.8 +/- 1.9 to 32.3 +/- 1.9% (P less than 0.05), minimal urine osmolality decreased from 59 +/- 3 to 46 +/- 3 mOsm/kg (P less than 0.01), and the diluting segment reabsorption index increased from 88.0 +/- 0.9 to 93.7 +/- 0.9%, P less than 0.01). Insulin also decreased plasma K, from 3.91 +/- 0.08 to 3.28 +/- 0.08 mmol/liter, P less than 0.01. In a third clearance study KCl was infused simultaneously (3.75 mumol/kg/min) to prevent this fall in plasma K. In this study insulin had no effect on Na and K excretion and diluting segment reabsorption, but the rise in FELi remained. In a fourth clearance study NaCl (3.75 mumol/kg/min) instead of KCl was infused together with insulin. This maneuver did not prevent the Na and K retaining effect of insulin, nor any of its effects on renal sodium handling parameters. These data suggest that Na and K retention during insulin infusion are largely secondary to hypokalemia, which causes increased reabsorption in the diluting segment.

  8. Sodium reabsorption in aldosterone-sensitive distal nephron: news and contributions from genetically engineered animals.

    PubMed

    Verrey, F

    2001-01-01

    The precise adaptation of renal sodium excretion to systemic needs is to a large extent achieved by the regulation of sodium re-absorption in the aldosterone-sensitive distal nephron. Transcellular sodium re-absorption by the segment-specific cells of the aldosterone-sensitive distal nephron (often called principal cells) is mainly controlled at the level of the expression and activity levels of the epithelial sodium channel, the apical amiloride-sensitive sodium influx pathway. Recent investigations have identified the first early aldosterone-induced proteins that act on epithelial sodium channel function in expression systems. Indirect evidence suggests that one of these aldosterone-induced proteins, the serum- and glucocorticoid-inducible protein kinase SGK1, plays a central integratory role in the control of epithelial sodium channel surface expression and activity, also in the mammalian kidney. Gene-modified animals lacking epithelial sodium channel subunits or expressing mutant subunits have substantiated the central role of the epithelial sodium channel in sodium re-absorption and blood pressure control, as well as for neonatal lung liquid clearance. Mice overexpressing or lacking specific hormones or their receptors have been used to study their role in sodium transport regulation, but the study of mouse physiology appears to lag behind the generation of gene-modified mice. Nonetheless, these new animal models have had a strong impact on research, by stimulating the integration of knowledge and techniques learned from reductionistic molecular approaches into tissue and animal studies, thus breaking down barriers and stimulating collaborations.

  9. Changes in Proximal and Distal Tubular Reabsorption Produced by Rapid Expansion of Extracellular Fluid*

    PubMed Central

    Hayslett, John P.; Kashgarian, Michael; Epstein, Franklin H.

    1967-01-01

    Acute infusions of isotonic saline in the rat cause an increase in glomerular filtration rate and in the excretion of salt and water. The kidney swells, due to expansion of tubular and interstitial volume. Despite the increase in tubular diameter, transit time through the proximal tubules and loops of Henle is decreased, presumably owing to a greatly accelerated rate of tubular flow. Proximal tubular reabsorption, measured in blocked tubules, is inhibited in a way that cannot be ascribed to changes in tubular diameter. The prolongation of proximal reabsorptive half-time is not affected by the administration of aldosterone. It occurs equally in rats chronically loaded with or deprived of salt, and it is therefore not likely that it is influenced by the renal content of renin. In contrast, reabsorption from the distal convoluted tubule is enhanced by saline infusion. This change is observed in segments of tubules blocked with oil and isolated from their glomeruli and thus appears to occur independently of changes in glomerular filtration or tubular flow. Images PMID:6027087

  10. Enhanced Distal Nephron Sodium Reabsorption in Chronic Angiotensin II Infused Mice

    PubMed Central

    Zhao, Di; Seth, Dale M.; Navar, L. Gabriel

    2009-01-01

    Chronic angiotensin II (Ang II) infusions enhance urinary excretion of angiotensinogen suggesting augmentation of distal nephron sodium reabsorption. To assess if chronic Ang II infusions (15 ng/min for 2 weeks) enhance distal nephron sodium reabsorption, we compared sodium excretion before and following blockade of the two main distal nephron sodium transporters by iv amiloride (5 mg/kg body weight) plus bendroflumethiazide (12 mg/kg body weight) in male C57/BL6 anesthetized control mice (n=10) and in chronic Ang II-infused mice (n=8). Chronic Ang II infusions increased systolic blood pressure to 141±6 mm Hg compared to 106±4 mm Hg in control mice. After anesthesia, mean arterial pressure averaged 97±4 mm Hg in chronic Ang II-infused mice compared with 94±3 mm Hg in control mice allowing comparison of renal function at similar arterial pressures. Ang II-infused mice had lower urinary sodium excretion (0.16±0.04 versus 0.30±0.05 μEq/min, P<0.05), higher distal sodium reabsorption (1.74±0.18 versus 1.12±0.18 μEq/min, P<0.05) and higher fractional reabsorption of distal sodium delivery (91.1±1.8% versus 77.9±4.3 %, P<0.05) than control mice. Urinary Ang II concentrations, measured during distal blockade, were greater in Ang II infused mice (1235.0±277.2 versus 468.9±146.9 fmol/ml, P<0.05). In chronic Ang II-infused mice treated with spironolactone (n=5), fractional reabsorption of distal sodium delivery was similarly augmented as in chronic Ang II infused mice (94.6±1.7%, P<0.01). These data provide in vivo evidence that there is enhanced distal sodium reabsorption dependent on sodium channel and Na+-Cl− cotransporter activity and increased urinary Ang II concentrations in mice infused chronically with Ang II. PMID:19487583

  11. Animal Models to Study Links between Cardiovascular Disease and Renal Failure and Their Relevance to Human Pathology

    PubMed Central

    Hewitson, Tim D.; Holt, Stephen G.; Smith, Edward R.

    2015-01-01

    The close association between cardiovascular pathology and renal dysfunction is well documented and significant. Patients with conventional risk factors for cardiovascular disease like diabetes and hypertension also suffer renal dysfunction. This is unsurprising if the kidney is simply regarded as a “modified blood vessel” and thus, traditional risk factors will affect both systems. Consistent with this, it is relatively easy to comprehend how patients with either sudden or gradual cardiac and or vascular compromise have changes in both renal hemodynamic and regulatory systems. However, patients with pure or primary renal dysfunction also have metabolic changes (e.g., oxidant stress, inflammation, nitric oxide, or endocrine changes) that affect the cardiovascular system. Thus, cardiovascular and renal systems are intimately, bidirectionally and inextricably linked. Whilst we understand several of these links, some of the mechanisms for these connections remain incompletely explained. Animal models of cardiovascular and renal disease allow us to explore such mechanisms, and more importantly, potential therapeutic strategies. In this article, we review various experimental models used, and examine critically how representative they are of the human condition. PMID:26441970

  12. [Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis].

    PubMed

    Kanashkina, T A; Kuznetsova, A A; Shakhmatova, E I; Natochin, Iu V

    2006-10-01

    In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.

  13. Are Sodium Transporters in Urinary Exosomes Reliable Markers of Tubular Sodium Reabsorption in Hypertensive Patients?

    PubMed Central

    Esteva-Font, Cristina; Wang, Xiaoyan; Ars, Elisabet; Guillén-Gómez, Elena; Sans, Laia; González Saavedra, Isabel; Torres, Ferran; Torra, Roser; Masilamani, Shyama; Ballarín, José Aurelio; Fernández-Llama, Patricia

    2010-01-01

    Background Altered renal sodium handling has a major pathogenic role in salt-sensitive hypertension. Renal sodium transporters are present in urinary exosomes. We hypothesized that sodium transporters would be excreted into the urine in different amounts in response to sodium intake in salt-sensitive versus salt-resistant patients. Methods Urinary exosomes were isolated by ultracentrifugation, and their content of Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC) was analyzed by immunoblotting. Animal studies: NKCC2 and NCC excretion was measured in 2 rat models to test whether changes in sodium transporter excretion are indicative of regulated changes in the kidney tissue. Human studies: in hypertensive patients (n = 41), we investigated: (1) a possible correlation between sodium reabsorption and urinary exosomal excretion of sodium transporters, and (2) the profile of sodium transporter excretion related to blood pressure (BP) changes with salt intake. A 24-hour ambulatory BP monitoring and a 24-hour urine collection were performed after 1 week on a low- and 1 week on a high-salt diet. Results Animal studies: urinary NKCC2 and NCC excretion rates correlated well with their abundance in the kidney. Human studies:6 patients (15%) were classified as salt sensitive. The NKCC2 and NCC abundance did not decrease after the high-salt period, when the urinary sodium reabsorption decreased from 99.7 to 99.0%. In addition, the changes in BP with salt intake were not associated with a specific profile of exosomal excretion. Conclusions Our results do not support the idea that excretion levels of NKCC2 and NCC via urinary exosomes are markers of tubular sodium reabsorption in hypertensive patients. PMID:20068364

  14. PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

    PubMed

    Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

    2016-06-01

    The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

  15. Evaluation of human fibroblast growth factor 23 (FGF-23) C-terminal and intact enzyme-linked immunosorbent-assays in end-stage renal disease patients.

    PubMed

    Fassbender, W J; Brandenburg, V; Schmitz, S; Sandig, D; Simon, S A; Windolf, J; Stumpf, U C

    2009-01-01

    Hyperphosphataemia, calcitriol deficency and secondary hyperparathyroidism (sHPT) are common complications in end-stage chronic kidney diseases (CKD). Fibroblast Growth Factor 23 (FGF-23) is a phosphaturic peptide, secreted by the osteoblast precursors, that also inhibits renal 1-alpha-hydroxylase activitiy and tubular phosphate reabsorption by the inhibition of sodium-dependant renal phosphate transport (Na-Pi-IIa). Consequences are a decreaese of serum 1,25 dihydroxyvitamin D3 and phosphaturia. Therefore, FGF-23 plays a role in hyperphosphataemia in association with CKD and may be involved in the pathogenesis of sHPT. Increased FGF-23 may contribute to maintaining a normal serum phoshpate level in face of a processing CKD, but if the creatinine clearance is reduced to lower than 30 ml/min the capacity of this regulative mechanism ends and hyperphosphataemia results. In our investigation of end-stage renal diseases markedly increased serum FGF-23, associated with hyperphosphataemia, phosphaturia and decreased serum calcitriol and sHPT, were found. Furthermore preanalytical testing for the stability of FGF-23 was performed by comparing samples which were stored at -20 degrees C with samples that have been stored for 6 days at +4 degrees C. The simultaneous investigation of serum and EDTA plasma FGF-23 certifies the advantage of EDTA plasma in subjects with an intact renal function.

  16. Integrin-linked kinase (ILK) expression correlates with tumor severity in clear cell renal carcinoma.

    PubMed

    Engelman, Míriam de Fátima Brasil; Grande, Rogério Mendes; Naves, Marcelo Andery; de Franco, Marcello Fabiano; de Paulo Castro Teixeira, Vicente

    2013-01-01

    Integrin-linked kinase (ILK) is an unique intracellular serine/threonine kinase and adapter protein. When dysregulated, it has been associated with increased cell proliferation, anchorage-independent cell growth, evasion of apoptosis, angiogenesis, invasion of surrounding tissues, downregulation of E-cadherin expression, nuclear translocation of β-catenin and metastasis, all features of tumoral malignancy. The objective of the present work was to evaluate the expression of ILK in clear cell renal carcinomas (CCRC) as a possible prognostic indicator. ILK immunoexpression was evaluated in a tissue microarray (TMA) with 45 human CCRCs. In addition, the apoptotic and proliferative indices and the immuno-expression of β-catenin and E-cadherin were also evaluated. E-cadherin expression was significantly decreased in tumors with positive ILK expression in relation to those with negative immunoexpression (p = 0.011). ILK immunostaining was significantly increased in high-grade in comparison to low-grade CCRCs (p = 0.0008). ILK expression was also associated with increased proliferative index (p = 0.020), tumor size >7.0 cm (p = 0.018) and with renal vein and capsule invasion (p = 0.003 and p = 0.00). Finally, tumors stage I and II (noninvasive) presented significantly reduced ILK immunoexpression when compared to stage III (locally invasive) (p = 0.0028). ILK immunoexpression in CCRC increases with loss of intercellular adhesion, nuclear grading, increased proliferative index and Robson stage. Altogether, our data suggest a possible role for ILK in the progression of CRCC.

  17. Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.

    PubMed

    Thomas, Joanna L; Pham, Hai; Li, Ying; Hall, Elanore; Perkins, Guy A; Ali, Sameh S; Patel, Hemal H; Singh, Prabhleen

    2017-08-01

    The pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch. We utilized the subtotal nephrectomy (STN) model of CKD to investigate the alterations in renal oxygenation linked to sodium (Na) transport and mitochondrial function in the surviving nephrons. Oxygen delivery was significantly reduced in STN kidneys because of lower renal blood flow. Fractional oxygen extraction was significantly higher in STN. Tubular Na reabsorption was significantly lower per mole of oxygen consumed in STN. We hypothesized that decreased mitochondrial bioenergetic capacity may account for this and uncovered significant mitochondrial dysfunction in the early STN kidney: higher oxidative metabolism without an attendant increase in ATP levels, elevated superoxide levels, and alterations in mitochondrial morphology. We further investigated the effect of activation of hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular hypoxia response. We observed significant improvement in renal blood flow, glomerular filtration rate, and tubular Na reabsorption per mole of oxygen consumed with HIF-1α activation. Importantly, HIF-1α activation significantly lowered mitochondrial oxygen consumption and superoxide production and increased mitochondrial volume density. In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism.

  18. X chromosome inactivation pattern in female carriers of X linked hypophosphataemic rickets.

    PubMed Central

    Orstavik, K H; Orstavik, R E; Halse, J; Knudtzon, J

    1996-01-01

    X linked hypophosphataemia (XLH) results from an abnormality of renal tubular phosphate reabsorption. The disorder is inherited as an X linked dominant trait and the gene has been mapped to Xp22.1-p22.2. A candidate gene (PEX) has recently been isolated. The most striking clinical features are growth retardation and skeletal abnormalities. As expected for X linked dominant disorders, females are less affected. However, such a gene dosage effect does not exist for renal phosphate reabsorption. Preferential X chromosome inactivation has been proposed as a possible explanation for this lack of gene dosage. We have examined the X inactivation pattern in peripheral blood cells from 12 females belonging to seven families with XLH using PCR analysis at the androgen receptor locus. The X inactivation pattern in these patients did not differ significantly from the pattern in 30 healthy females. The X inactivation pattern in peripheral blood cells does not necessarily reflect the X inactivation pattern in renal cells. However, the finding of a normal distribution of X inactivation in peripheral blood cells indicates that the similarity in the renal handling of phosphate in male and female patients is not related to a ubiquitous preferential X inactivation. Images PMID:8863165

  19. Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease.

    PubMed

    Nielsen, Rikke; Christensen, Erik Ilsø; Birn, Henrik

    2016-01-01

    Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated with dysfunction of these receptors have been identified and characterized, providing additional information on the importance of these receptors in humans. Using various disease models in combination with receptor gene knockout, the implications of receptor dysfunction in acute and chronic kidney injury have been explored and have pointed to potential new roles of these receptors. Based on data from animal models, this paper will review current knowledge on proximal tubule endocytic receptor function and regulation, and their role in renal development, protein reabsorption, albumin uptake, and normal renal physiology. These findings have implications for the pathophysiology and diagnosis of proteinuric renal diseases. We will examine the limitations of the different models and compare the findings to phenotypic observations in inherited human disorders associated with receptor dysfunction. Furthermore, evidence from receptor knockout mouse models as well as human observations suggesting a role of protein receptors for renal disease will be discussed in light of conditions such as chronic kidney disease, diabetes, and hypertension.

  20. Parenchymal injury in remnant-kidney model may be linked to apoptosis of renal cells mediated by nitric oxide.

    PubMed

    Hruby, Zbigniew; Rosinski, Maciej; Tyran, Bronislaw

    2008-01-01

    The importance of apoptotic cell death in the pathogenesis of progressive renal sclerosis has been well established. While activity of vasorelaxant nitric oxide is conceivable in the remnant hyperfiltrating kidney and nitric oxide has been reported to cause apoptosis, we postulated that this mechanism of cell death may be operating in progressive renal fibrosis. The intensity of apoptosis in glomerular and tubular cells was assessed (light microscopy, TUNEL method) in the remnant-kidney model of progressive renal fibrosis in rats undergoing 5/6 nephrectomy. Numbers of apoptotic cells were correlated with expression of mRNA for inducible nitric oxide synthase (iNOS; RT-PCR in situ), generation of nitrite in renal tissue, an index of glomerulosclerosis, proteinuria and creatinine clearance. A control group of 5/6 nephrectomized rats received an iNOS inhibitor, L-NAME, in drinking water during the 4 weeks after nephrectomy. Number of apoptotic cells gradually increased in experimental rats both in glomeruli and tubules, until termination of the study 3 months after 5/6 nephrectomy. At 3 months postinduction, the intensity of tubular cell apoptosis was significantly correlated with creatinine clearance (p<0.05), while glomerular cell apoptosis was correlated with the index of glomerulosclerosis, also at 3 months (p<0.0025). Along with the apoptosis, the levels of iNOS mRNA for, and generation of, nitrite in renal tissue had risen until termination of the study. The generation of nitrites correlated with the number of apoptotic glomerular cells (p<0.025). Treatment with the iNOS inhibitor resulted in a significant reduction in number of apoptotic cells (p<0.01). Apoptotic depletion of renal tubular and glomerular cells linked to activity of iNOS may contribute to progression of chronic kidney tissue injury in the 5/6 nephrectomy model.

  1. NEK8 Links the ATR-regulated Replication Stress Response and S-phase CDK Activity to Renal Ciliopathies

    PubMed Central

    Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G.; Kile, Andrew C.; Paulsen, Renee D.; Manning, Danielle K.; Beier, David R.; Giles, Rachel H.; Boulton, Simon J.; Cimprich, Karlene A.

    2013-01-01

    Summary Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) which further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

  2. NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies.

    PubMed

    Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G; Kile, Andrew C; Paulsen, Renee D; Manning, Danielle K; Beier, David R; Giles, Rachel H; Boulton, Simon J; Cimprich, Karlene A

    2013-08-22

    Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) that further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders.

  3. Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

    PubMed Central

    Cano-Peñalver, José Luis; Griera, Mercedes; García-Jerez, Andrea; Hatem-Vaquero, Marco; Ruiz-Torres, María Piedad; Rodríguez-Puyol, Diego; de Frutos, Sergio; Rodríguez-Puyol, Manuel

    2015-01-01

    Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis–related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS-dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage. PMID:26562149

  4. Patterned dye structures limit reabsorption in luminescent solar concentrators.

    PubMed

    Tsoi, Shufen; Broer, Dirk J; Bastiaansen, Cees W; Debije, Michael G

    2010-11-08

    This work describes a method for limiting internal losses of a luminescent solar concentrator (LSC) due to reabsorption through patterning the fluorescent dye doped coating of the LSC. By engineering the dye coating into regular line patterns with fill factors ranging from 20 - 80%, the surface coverage of the dye molecules were reduced, thereby decreasing the probability of the re-emitted light encountering another dye molecule and the probability of reabsorption. Two types of fluorescent dyes with different quantum yields were used to examine the effects of patterning on LSC performance. The effect of various dimension and geometry of the patterns on the efficiency and edge emission of LSC are presented and analyzed.

  5. PGC1α-dependent NAD biosynthesis links oxidative metabolism to renal protection

    PubMed Central

    Tran, Mei T.; Zsengeller, Zsuzsanna K.; Berg, Anders H.; Khankin, Eliyahu V.; Bhasin, Manoj K.; Kim, Wondong; Clish, Clary B.; Stillman, Isaac E.; Karumanchi, S. Ananth; Rhee, Eugene P.; Parikh, Samir M.

    2016-01-01

    The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischemia. Indeed, acute kidney injury (AKI) affects 3% of all hospitalized patients.1,2 Here we show that the mitochondrial biogenesis regulator, PGC1α,3,4 is a pivotal determinant of renal recovery from injury by regulating NAD biosynthesis. Following renal ischemia, PGC1α−/− mice developed local deficiency of the NAD precursor niacinamide (Nam), marked fat accumulation, and failure to re-establish normal function. Remarkably, exogenous Nam improved local NAD levels, fat accumulation, and renal function in post-ischemic PGC1α−/− mice. Inducible tubular transgenic mice (iNephPGC1α) recapitulated the effects of Nam supplementation, including more local NAD and less fat accumulation with better renal function after ischemia. PGC1α coordinately upregulated the enzymes that synthesize NAD de novo from amino acids whereas PGC1α deficiency or AKI attenuated the de novo pathway. Nam enhanced NAD via the enzyme NAMPT and augmented production of the fat breakdown product beta-hydroxybutyrate (β-OHB), leading to increased prostaglandin PGE2, a secreted autocoid that maintains renal function.5 Nam treatment reversed established ischemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of β-OHB signaling or prostaglandins similarly abolished PGC1α-dependent renoprotection. Given the importance of mitochondrial health in aging and the function of metabolically active organs, the results implicate Nam and NAD as key effectors for achieving PGC1α-dependent stress resistance. PMID:26982719

  6. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection.

    PubMed

    Tran, Mei T; Zsengeller, Zsuzsanna K; Berg, Anders H; Khankin, Eliyahu V; Bhasin, Manoj K; Kim, Wondong; Clish, Clary B; Stillman, Isaac E; Karumanchi, S Ananth; Rhee, Eugene P; Parikh, Samir M

    2016-03-24

    The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischaemia. Acute kidney injury (AKI) affects 3% of all hospitalized patients. Here we show that the mitochondrial biogenesis regulator, PGC1α, is a pivotal determinant of renal recovery from injury by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis. Following renal ischaemia, Pgc1α(-/-) (also known as Ppargc1a(-/-)) mice develop local deficiency of the NAD precursor niacinamide (NAM, also known as nicotinamide), marked fat accumulation, and failure to re-establish normal function. Notably, exogenous NAM improves local NAD levels, fat accumulation, and renal function in post-ischaemic Pgc1α(-/-) mice. Inducible tubular transgenic mice (iNephPGC1α) recapitulate the effects of NAM supplementation, including more local NAD and less fat accumulation with better renal function after ischaemia. PGC1α coordinately upregulates the enzymes that synthesize NAD de novo from amino acids whereas PGC1α deficiency or AKI attenuates the de novo pathway. NAM enhances NAD via the enzyme NAMPT and augments production of the fat breakdown product β-hydroxybutyrate, leading to increased production of prostaglandin PGE2 (ref. 5), a secreted autacoid that maintains renal function. NAM treatment reverses established ischaemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of β-hydroxybutyrate signalling or prostaglandin production similarly abolishes PGC1α-dependent renoprotection. Given the importance of mitochondrial health in ageing and the function of metabolically active organs, the results implicate NAM and NAD as key effectors for achieving PGC1α-dependent stress resistance.

  7. Pharmacokinetics of propionyl-l-carnitine in humans: evidence for saturable tubular reabsorption

    PubMed Central

    Pace, S; Longo, A; Toon, S; Rolan, P; Evans, A M

    2000-01-01

    Aims Propionyl-l-carnitine (PLC) is an endogenous compound which, along with l-carnitine (LC) and acetyl-l-carnitine (ALC), forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC is currently under investigation for the treatment of peripheral artery disease, and the present study was conducted to assess the pharmacokinetics of intravenous propionyl-l-carnitine hydrochloride. Methods This was a placebo-controlled, double-blind, parallel group, dose-escalating study in which 24 healthy males were divided into four groups of six. Four subjects from each group received propionyl-l-carnitine hydrochloride and two received placebo. The doses (1 g, 2 g, 4 g and 8 g) were administered as a constant rate infusion over 2 h and blood and urine were collected for 24 h from the start of the infusion. PLC, ALC and LC in plasma and urine were quantified by h.p.l.c. Results All 24 subjects successfully completed the study and the infusions were well tolerated. In addition to the expected increase in PLC levels, the plasma concentrations and urinary excretion of LC and ALC also increased above baseline values following intravenous propionyl-l-carnitine hydrochloride administration. At a dose of 1 g, PLC was found to have a mean (± s.d.) half-life of 1.09 ± 0.15 h, a clearance of 11.6 ± 0.24 l h−1 and a volume of distribution of 18.3 ± 2.4 l. None of these parameters changed with dose. In placebo-treated subjects, endogenous PLC, LC and ALC underwent extensive renal tubular reabsorption, as indicated by renal excretory clearance to GFR ratios of less than 0.1. The renal-excretory clearance of PLC, which was 0.33 ± 0.38 l h−1 under baseline condition, increased (P < 0.001) from 1.98 ± 0.59 l h−1 at a dose of 1 g to 5.55 ± 1.50 l h−1 at a dose of 8 g (95% confidence interval for the difference was 2.18,4.97). As a consequence, the percent of the dose excreted unchanged in urine increased (P < 0.001) from 18.1 ± 5.5% (1 g

  8. Glucagon-like peptide-1 receptor stimulation increases GFR and suppresses proximal reabsorption in the rat.

    PubMed

    Thomson, Scott C; Kashkouli, Ali; Singh, Prabhleen

    2013-01-15

    The incretin hormone glucagon-like peptide-1 (GLP-1) is released from the gut in response to fat or carbohydrate and contributes to negative feedback control of blood glucose by stimulating insulin secretion, inhibiting glucagon, and slowing gastric emptying. GLP-1 receptors (GLP-1R) are also expressed in the proximal tubule, and possibly elsewhere in the kidney. Presently, we examined the effect of a GLP-1R agonist on single-nephron glomerular filtration rate (GFR; SNGFR), proximal reabsorption (Jprox), tubuloglomerular feedback (TGF) responses, and urine flow rate in hydropenic male Wistar and Wistar-Froemter rats. Micropuncture and whole-kidney data were obtained before and during infusion of the GLP-1 agonist exenatide (1 nmol/h iv). SNGFR and Jprox were measured by late proximal collection at both extremes of TGF activation, which was achieved by perfusing Henle's loop at 0 or 50 nl/min. Primary changes in Jprox were revealed by analysis of covariance for Jprox with SNGFR as a covariate. Effects on TGF activation were determined in a separate set of experiments by comparing early distal and late proximal collections. Exenatide increased SNGFR by 33-50%, suppressed proximal tubular reabsorption by 20-40%, doubled early distal flow rate, and increased urine flow rate sixfold without altering the efficiency of glomerulotubular balance, TGF responsiveness, or the tonic influence of TGF. This implies that exenatide is both a proximal diuretic and a renal vasodilator. Since the natural agonist for the GLP-1R is regulated by intake of fat and carbohydrate, but not by salt or fluid, the control of salt excretion by the GLP-1R system departs from the usual negative-feedback paradigm for regulating salt balance.

  9. Hypouricaemia and hyperuricosuria in familial renal glucosuria

    PubMed Central

    Aires, Inês; Santos, Ana Rita; Pratas, Jorge; Nolasco, Fernando; Calado, Joaquim

    2013-01-01

    Familial renal glucosuria is a rare co-dominantly inherited benign phenotype characterized by the presence of glucose in the urine. It is caused by mutations in the SLC5A2 gene that encodes SGLT2, the Na+-glucose cotransporter responsible for the reabsorption of the bulk of glucose in the proximal tubule. We report a case of FRG displaying both severe glucosuria and renal hypouricaemia. We hypothesize that glucosuria can disrupt urate reabsorption in the proximal tubule, directly causing hyperuricosuria. PMID:26064518

  10. Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium

    PubMed Central

    Wuttke, Matthias; Wong, Craig S.; Wühl, Elke; Epting, Daniel; Luo, Li; Hoppmann, Anselm; Doyon, Anke; Li, Yong; Sözeri, Betül; Thurn, Daniela; Helmstädter, Martin; Huber, Tobias B.; Blydt-Hansen, Tom D.; Kramer-Zucker, Albrecht; Mehls, Otto; Melk, Anette; Querfeld, Uwe; Furth, Susan L.; Warady, Bradley A.; Schaefer, Franz; Köttgen, Anna

    2016-01-01

    Background Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown. Methods The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from >10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 1136 patients with measurements of serum creatinine at study enrolment. Genome-wide association studies were conducted to relate the SNPs to creatinine-based estimated glomerular filtration rate (eGFRcrea) and proteinuria (urinary albumin- or protein-to-creatinine ratio ≥300 and ≥500 mg/g, respectively). In addition, European-ancestry PediGFR patients (cases) were compared with 1347 European-ancestry children without kidney disease (controls) to identify genetic variants associated with the presence of CKD. Results SNPs with suggestive association P-values <1×10−5 were identified in 10 regions for eGFRcrea, four regions for proteinuria and six regions for CKD including some plausible biological candidates. No SNP was associated at genome-wide significance (P < 5×10−8). Investigation of the candidate genes for proteinuria in adults from the general population provided support for a region on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation of genes harboring GFR-associated variants in adults from the general population did not reveal significantly associated SNPs in

  11. Novel phosphate-regulating genes in the pathogenesis of renal phosphate wasting disorders.

    PubMed

    Tenenhouse, Harriet S; Sabbagh, Yves

    2002-06-01

    Over the past decade, three classes of Na/Pi cotransporters have been identified in mammalian kidney. The type IIa Na/Pi cotransporter, Npt2, is the most abundant and is expressed in the brush-border membrane of renal proximal tubular cells where the bulk of filtered inorganic phosphate (Pi) is reabsorbed. Disruption of the Npt2 gene in mice underscored the importance of Npt2 in the overall maintenance of Pi homeostasis and demonstrated that Npt2 is the target for regulation of proximal tubular Pi reabsorption by parathyroid hormone and dietary Pi. The regulation is post-transcriptional and largely occurs by brush-border membrane retrieval and insertion of Npt2 protein. Of great interest is the recent identification of novel Pi regulating genes, PHEX and FGF23, that play a role in the pathophysiology of inherited (X-linked hypophosphatemia and autosomal dominant hypophosphatemic rickets) and acquired (oncogenic hypophosphatemic rickets) disorders characterized by renal Pi wasting and associated skeletal abnormalities. Studies are currently underway to elucidate the molecular basis for impaired renal Pi reabsorption in these disorders and to determine the precise physiological role of PHEX and FGF-23 in the regulation of Pi homeostasis.

  12. Renal elimination of perfluorocarboxylates (PFCAs).

    PubMed

    Han, Xing; Nabb, Diane L; Russell, Mark H; Kennedy, Gerald L; Rickard, Robert W

    2012-01-13

    Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasis on their relevance to renal elimination. PFCAs vary in their affinities to bind to serum albumins in plasma, which is an important factor in determining the renal clearance of PFCAs. PFCA-albumin binding has been well characterized and is summarized in this review. The mechanism of the sex-, species-, and chain length-dependent renal PFCA elimination is a research area that has gained continuous interest since the beginning of toxicological studies of PFCAs. It is now recognized that organic anion transport proteins play a key role in PFCA renal tubular reabsorption, a process that is sex-, species-, and chain length-dependent. Recent studies on the identification of PFCA renal transport proteins and characterization of their transport kinetics have greatly improved our understanding of the PFCA renal transport mechanism at the molecular level. A mathematical representation of this renal tubular reabsorption mechanism has been incorporated in physiologically based pharmacokinetic (PBPK) modeling of perfluorooctanoate (PFOA). Improvement of PBPK models in the future will require more accurate and quantitative characterization of renal transport pathways of PFCAs. To that end, a basolateral membrane efflux pathway for the reabsorption of PFCAs in the kidney is discussed in this review, which could provide a future research direction toward a better understanding of the mechanisms of PFCA renal elimination.

  13. Job stress strengthens the link between metabolic risk factors and renal dysfunction in adult men.

    PubMed

    Tsurugano, Shinobu; Nakao, Mutsuhiro; Takeuchi, Takeaki; Nomura, Kyoko; Yano, Eiji

    2012-01-01

    Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease. The metabolic risk factors obesity, hypertension, diabetes, and dyslipidemia are closely associated with renal dysfunction. As psychosocial stress affects these risk factors, here, we examined relationships between metabolic risk factors and renal function, and their association with job stress. The participants were 1,231 Japanese male office workers attending annual health examinations. The estimated glomerular filtration rate (eGFR) was determined using the equation recommended by the Japanese Society for Nephrology: eGFR (mL/min/1.73 m(2)) = 194 × age(-0.287) × Cr(-1.094). Job stress was measured using the Job Content Questionnaire based on the job demand-control model. The job strain index equaled the job demand scores divided by the job control scores. The participants were classified into four ordinal groups of job strain index, based on previous studies (i.e., ≤ 0.4 the lowest, 0.4-0.5 lower, 0.5-0.6 higher, or ≥ 0.6 the highest). A significant correlation was found between lowered eGFR and each of the metabolic risk factors waist circumference, systolic and diastolic blood pressure, and total cholesterol (p < 0.001). Furthermore, job stress had an interactive effect on the relationships between eGFR and systolic and diastolic blood pressure, and triglycerides, depending on the job strain index (highest vs. lowest) (p < 0.05). The highly stressed workers exhibited a close association of eGFR with metabolic risk factors like hypertension and dyslipidemia. Therefore, intensive management may be important for preventing the progression of renal dysfunction and cardiovascular complications in those experiencing stress.

  14. The innervation of the kidney in renal injury and inflammation: A cause and consequence of deranged cardiovascular control.

    PubMed

    Abdulla, Mohammed H; Johns, Edward J

    2017-02-09

    Extensive investigations have revealed that renal sympathetic nerves regulate renin secretion, tubular fluid reabsorption and renal haemodynamics which can impact on cardiovascular homoeostasis normally and in pathophysiological states. The significance of the renal afferent innervation and its role in determining the autonomic control of the cardiovascular system is uncertain. The transduction pathways at the renal afferent nerves have been shown to require pro-inflammatory mediators and TRPV1 channels. Reno-renal reflexes have been described, both inhibitory and excitatory, demonstrating that a neural link exists between kidneys and may determine the distribution of excretory and haemodynamic function between the two kidneys. The impact of renal afferent nerve activity on basal and reflex regulation of global sympathetic drive remains opaque. There is clinical and experimental evidence that in states of chronic kidney disease and renal injury there is infiltration of T-helper cells with a sympatho-excitation and blunting of the high and low pressure baroreceptor reflexes regulating renal sympathetic nerve activity. The baroreceptor deficits are renal nerve-dependent as the dysregulation can be relieved by renal denervation. There is also experimental evidence that in obese states there is a sympatho-excitation and disrupted baroreflex regulation of renal sympathetic nerve activity which is mediated by the renal innervation. This body of information provides an important basis for directing greater attention to the role of renal injury/inflammation causing an inappropriate activation of the renal afferent nerves as an important initiator of aberrant autonomic cardiovascular control. This article is protected by copyright. All rights reserved.

  15. Fluid reabsorption by the ductuli efferentes testis of the rat is dependent on both sodium and chlorine.

    PubMed

    Hansen, Lyall A; Dacheux, Françoise; Man, Suet Yee; Clulow, John; Jones, Russell C

    2004-08-01

    The role of Na(+) and Cl(-) in fluid reabsorption by the efferent ducts was examined by perfusing individual ducts in vivo with preparations of 160 mM NaCl in which the ions were replaced, together or individually, with organic solutes while maintaining the osmolality at 300 mmol/kg. Progressively replacing NaCl with mannitol reduced net reabsorption of water and the ions in a concentration-dependent manner, and caused net movement into the lumen at concentrations of NaCl less than 80 mM. The net rates of flux were lower for Na(+) than for Cl(-). In collectates, [Na(+)] was greater than [Cl(-)], indicating that Cl(-) transport is probably linked with another anion. Replacing either Na(+) or Cl(-) in perfusates (with choline and isethionate, respectively) while maintaining the other inorganic ion at 160 mM also reduced net rates of reabsorption in a concentration-dependent manner to zero when either ion was completely replaced. There were no significant differences in the osmolality of perfusate and collectate, and collectates contained a mean of 3.4 mM K(+), indicating a backflux of K(+) into the lumen. It is concluded that fluid reabsorption from the efferent ducts is dependent on the transport of both Na(+) and Cl(-) from the lumen (from a luminal concentration of at least 70-80 mM), and that Cl(-) transport is dependent on another anion. The epithelium is permeable to K(+) and has a higher permeability to a range of organic solutes (mannitol, choline, and isethionate) than epithelium in the proximal kidney tubules.

  16. Renal conservation of ketone bodies during starvation.

    PubMed

    Sapir, D G; Owen, O E

    1975-01-01

    Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

  17. Regulation of renal NaCl and water transport by the ATP/UTP/P2Y2 receptor system

    PubMed Central

    Rieg, Timo

    2011-01-01

    Extracellular nucleotides (e.g., ATP) activate ionotropic P2X and metabotropic P2Y receptors in the plasma membrane to regulate and maintain cell function and integrity. This includes the renal tubular and collecting duct system, where the locally released nucleotides act in a paracrine and autocrine way to regulate transport of electrolytes and water and maintain cell volume. A prominent role has been assigned to Gq-coupled P2Y2 receptors, which are typically activated by both ATP and UTP. Studies in gene knockout mice revealed an antihypertensive activity of P2Y2 receptors that is linked to vasodilation and an inhibitory influence on renal salt reabsorption. Flow induces apical ATP release in the thick ascending limb, and first evidence indicates an inhibitory influence of P2Y2 receptor tone on the expression and activity of the Na-K-2Cl cotransporter NKCC2 in this segment. The apical ATP/UTP/P2Y2 receptor system in the connecting tubule/cortical collecting duct mediates the inhibitory effect of dietary salt on the open probability of the epithelial sodium channel ENaC and inhibits ENaC activity during aldosterone escape. Connexin 30 has been implicated in the luminal release of the ATP involved in the regulation of ENaC. An increase in collecting duct cell volume in response to manipulating water homeostasis increases ATP release. The subsequent activation of P2Y2 receptors inhibits vasopressin-induced cAMP formation and water reabsorption, which facilitates water excretion and stabilizes cell volume. Thus recent studies have established the ATP/UTP/P2Y2 receptor system as a relevant regulator of renal salt and water homeostasis and blood pressure regulation. The pathophysiological relevance and therapeutic potential remains to be determined, but dual effects of P2Y2 receptor activation on both the vasculature and renal salt reabsorption implicate these receptors as potential therapeutic targets in hypertension. PMID:21715471

  18. Metabolic alkalosis in the rat. Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state.

    PubMed Central

    Cogan, M G; Liu, F Y

    1983-01-01

    Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5 +/- 0.9 mM (vs. 27.7 +/- 0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4 +/- 1.5 vs. 51.6 +/- 1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981 +/- 49 vs. 1,081 +/- 57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium and chloride depletion. In all cases, the rise in blood bicarbonate concentration was inversely proportional to a reduction in GFR; filtered bicarbonate load remained normal. In conclusion, a reduction in GFR is proposed as being critical for maintaining chronic metabolic alkalosis in the rat. Constancy of the filtered bicarbonate load allows normal rates of renal bicarbonate reabsorption to maintain the alkalotic state. Images PMID:6853706

  19. βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma.

    PubMed

    Quaas, Alexander; Rahvar, Amir-Hossein; Burdelski, Christoph; Koop, Christina; Eichelberg, Christian; Rink, Michael; Dahlem, Roland; Schlomm, Thorsten; Tsourlakis, Maria Christina; Simon, Ronald; Minner, Sarah; Sauter, Guido; Steurer, Stefan

    2015-10-01

    βIII-tubulin (TUBB3) is a microtubule component overexpression of which is found in many solid cancer types, often linked to poor patient prognosis, and has been suggested to predict failure of microtubule-targeting chemotherapeutics. This study was designed to determine prevalence and prognostic impact of TUBB3 expression in kidney cancers. A tissue microarray (TMA) containing more than 1,200 renal tumors was analyzed by immunohistochemistry. TUBB3 expression varied markedly between the different histological subtypes and was more frequent in 105 papillary cancers (75.2 %, p < 0.0001), 38 oncocytomas (52.6 %, p < 0.0001), and 22 chromophobic carcinomas (36.4 %, p = 0.1221) than in 555 clear cell RCC (16.4 %). In clear cell cancers, strong TUBB3 positivity was linked to high Fuhrman grade (p < 0.0001), advanced stage (0.002), nodal metastases (p = 0.0433), hematogenous metastases (p = 0.0016), and shortened overall survival (p < 0.0001). Associations with outcome and tumor phenotype were inversely for papillary RCC, where TUBB3 immunostaining was linked to low tumor stage (p = 0.0012) and prolonged survival (p = 0.0043). TUBB3 expression levels and their effects are strikingly different between ccRCC and papillary RCC. These differences may be caused by differences in VHL function between these RCC subtypes, because VHL (like TUBB3) is another strong regulator of microtubule function.

  20. [Investigation of tubular reabsorption of phosphates in patients with chronic kidney disease].

    PubMed

    Horáčková, Miroslava; Schück, Otto; Sotorník, Ivo; Franková, Janka; Štollová, Milena; Látová, Irena; Malinská, Hana; Urbanová, Jana

    2015-12-01

    nephrons). The values of in(FEPi) were higher in all patients with CKD than kr(FEPi) as expected, likely because the value CKr decreases at a slower rate than Cin (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons. The results of this study support the assumption that, provided the values of kr(FEPi) which are easily measurable in clinical practice have reached 50-60%, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered.

  1. Acetazolamide serves as selective delivery vehicle for dipeptide-linked drugs to renal cell carcinoma

    PubMed Central

    Cazzamalli, Samuele; Dal Corso, Alberto; Neri, Dario

    2016-01-01

    In most cases, cytotoxic drugs do not preferentially accumulate at the tumor site, causing unwanted toxicities and preventing dose escalation to therapeutically active regimens. Here, we show that acetazolamide derivatives, which bind to carbonic anhydrase IX (CAIX) on the surface of kidney cancer cells, selectively deliver payloads at the site of disease, sparing normal organs. Biodistribution studies, performed in tumor-bearing mice with acetazolamide derivatives bearing a technetium-99m chelator complex or a red fluorophore as payload, revealed a preferential tumor accumulation of the compound at doses up to 560 nmol/Kg. The percentage of injected dose per gram in the tumor was dose-dependent and revealed optimal tumor:organ ratios at 140 nmol/Kg, with a tumor:blood ratio of 80:1 at 6 h. Acetazolamide, coupled to potent cytotoxic drugs via a dipeptide linker, exhibited a potent antitumor activity in nude mice bearing SKRC-52 renal cell carcinomas, while drug derivatives devoid of the acetazolamide moiety did not exhibit any detectable anticancer activity at the same doses. The observation of tumor regression with a noninternalizing ligand and with different cytotoxic moieties (MMAE and PNU-159682) indicates a general mechanism of action, based on the selective accumulation of the product on tumor cells, followed by the extracellular proteolytic release of the cytotoxic payload at the neoplastic site and the subsequent drug internalization into tumor cells. Acetazolamide-based drug conjugates may represent a promising class of targeted agents for the treatment of metastatic kidney cancer, as the majority of human clear cell renal cell carcinomas are strongly positive for CAIX. PMID:27609641

  2. Renal tubular acidosis.

    PubMed

    Chan, J C

    1983-03-01

    In the past decade major advances in our understanding of renal tubular hydrogen ion secretion and bicarbonate reabsorption have provided new insight into the pathophysiology of renal tubular acidosis. Thus "fragment to fragment clings" and the number of disorders categorized within the syndrome grows, until we have come to know and name four types, with many subtypes. We hope this new perspective provides a basis for the physician to recognize renal tubular acidosis in its several forms so that an informed decision may be arrived at in choosing the best therapy. The physician may also be prepared to reasonably project the prognosis for each patient. We also hope that our detailed examination of renal acidification will provide a reference for delineation of new clinical expressions of acid-base disorders and kidney malfunction certain to be described in the years ahead.

  3. [Effect of Chinese herbal medicine with Supplement Qi and Activating Blood Circulation on tubular reabsorption function of diabetic nephropathy rats].

    PubMed

    Yin, Juan-Juan; Yang, Ye; Wang, Qing-Bao; Li, Yun; Yin, Deng-Ke

    2013-06-01

    To investigate the effect of Chinese herbal medicine with Supplement Qi and Activating Blood Circulation (huangqi and danshen) on urinary protein, kidney function and tubular reabsorption of diabetic nephropathy rats. SD rats were randomly divided into a nondiabetic control group (normal group) and three groups in which diabetes were induced by a single intraperitoneal injection of freshly prepared streptozotocin( STZ,55 mg/kg body weight). Then the diabetes rats were randomly assigned to three groups: diabetic model group, Supplement Qi and Activating Blood Circulation traditional Chinese medicine group (huangqi and danshen group) and Gliquidone group (as a reference hypoglycemic drug). Each group was treated with corresponding drugs for 6 weeks. At the end of the study, the rats from each group were injected with FITC-labeled BSA through tail vein. The 24 h urinary protein excretion were measured and blood was collected for measuring plasma glucose levels, serum creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG) and total cholesterol (T-CHO). Renal tissue was used to measure the level of LPO,SOD,GSH-Px and AGEs and Paraffin-embedded sections were stained with HE, PAS and immunohistochemistry. The plasma glucose, the 24 h urinary protein excretion, the levels of serum Cr, BUN, TG and T-CHO in STZ-induced diabetic rats were higher than those of nondiabetic rats. Diabetic rats showed significantly increase in LPO and AGEs (P < 0.01) and decrease in antioxidant enzyme activity (both GSH-Px and SOD) (P < 0.05) as compared with non-diabetic control rats. Treatment with the Supplement Qi and Activating Blood Circulation traditional Chinese medicine for 6 weeks in diabetic rats significantly reduced the 24 h urinary protein excretion compared with model control (P < 0.01), and markedly decreased the levels of serum Cr,BUN,TG and T-CHO as compared with those of diabetic rat (P < 0.05). The levels of LPO and AGEs were decreased and the activity of GSH-Px was

  4. Increased Milk Protein Concentration in a Rehydration Drink Enhances Fluid Retention Caused by Water Reabsorption in Rats.

    PubMed

    Ito, Kentaro; Saito, Yuri; Ashida, Kinya; Yamaji, Taketo; Itoh, Hiroyuki; Oda, Munehiro

    2015-01-01

    A fluid-retention effect is required for beverages that are designed to prevent dehydration. That is, fluid absorbed from the intestines should not be excreted quickly; long-term retention is desirable. Here, we focused on the effect of milk protein on fluid retention, and propose a new effective oral rehydration method that can be used daily for preventing dehydration. We first evaluated the effects of different concentrations of milk protein on fluid retention by measuring the urinary volumes of rats fed fluid containing milk protein at concentrations of 1, 5, and 10%. We next compared the fluid-retention effect of milk protein-enriched drink (MPD) with those of distilled water (DW) and a sports drink (SD) by the same method. Third, to investigate the mechanism of fluid retention, we measured plasma insulin changes in rats after ingesting these three drinks. We found that the addition of milk protein at 5 or 10% reduced urinary volume in a dose-dependent manner. Ingestion of the MPD containing 4.6% milk protein resulted in lower urinary volumes than DW and SD. MPD also showed a higher water reabsorption rate in the kidneys and higher concentrations of plasma insulin than DW and SD. These results suggest that increasing milk protein concentration in a beverage enhances fluid retention, which may allow the possibility to develop rehydration beverages that are more effective than SDs. In addition, insulin-modifying renal water reabsorption may contribute to the fluid-retention effect of MPD.

  5. Usefulness of kidney slices for functional analysis of apical reabsorptive transporters.

    PubMed

    Arakawa, Hiroshi; Washio, Ikumi; Matsuoka, Natsumi; Kubo, Hikaru; Staub, Angelina Yukiko; Nakamichi, Noritaka; Ishiguro, Naoki; Kato, Yukio; Nakanishi, Takeo; Tamai, Ikumi

    2017-10-09

    Kidney plays a key role in the elimination and reabsorption of drugs and nutrients, however in vitro methods to evaluate renal disposition are limited. In the present study, we investigated usefulness of isolated kidney slice, which had been used for transport only at basolateral membrane of tubular epithelial cells, for evaluation of apical membrane transporters. As transporters that are easy to discriminate between apical and basolateral transports, apical membrane specific and sodium-dependent transporters (SGLTs and OCTNs) and pH-dependent transporters (PEPTs) are selected. Uptake of ergothioneine, carnitine and methyl-α-D-glucopyranoside, which are substrates of apical Octn1, Octn2, and Sglt1/2, respectively, by mice kidney slices showed clear Na(+) dependence and reduction by selective inhibitors. In addition, sodium dependence of ergothioneine uptake was negligible in the kidney slice from Octn1-gene deficient mice. Moreover, uptake of PepT1/2 substrate glycyl-sarcosine, was higher than that in the presence of glycyl-leucine, a non-specific Pept inhibitor. The K m and IC 50 values for substrates and inhibitors of each transporter were mostly comparable to those obtained in transporter-transfected cells. In conclusion, it was demonstrated that kidney slices are promising tool to study transporters expressed at the apical membranes as well as basolateral membranes of kidney tubular epithelial cells.

  6. Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats.

    PubMed

    Susic, Dinko; Varagic, Jasmina; Ahn, Jwari; Frohlich, Edward D

    2004-04-01

    Increased formation of advanced glycosylation end-products on body proteins is a consequence of aging and leads to exaggerated collagen cross-linking eventually increasing cardiovascular stiffness. This study reports our initial inquires into the cardiovascular and renal effects of a cross-link breaker (ALT-711) in aged spontaneously hypertensive rats (SHR). The first experiment, in 45-week-old SHR, showed that (among four doses) the dose of 1 mg/kg/d of ALT-711 given for 4 months was most effective in reducing left ventricular and aortic mass indexes. ALT-711 also reduced left ventricular hydroxyproline concentration (5.8 +/- 0.2 v 5.1 +/- 0.3 mg/g in controls, P < .05); however, it did not affect systemic or regional hemodynamics. In older SHR, ALT-711 (1 mg/kg/d) reduced (P < .05) systolic pressure (tail-cuff) (from 203 +/- 3 mm Hg at outset to 187 +/- 3 mm Hg at 8 weeks). Systolic pressure remained unchanged in placebo-treated rats. In addition, left ventricular index (3.09 +/- 0.10 v 3.44 +/- 0.05 mg/g) and aortic mass index (1.54 +/- 0.04 v 1.74 +/- 0.05 mg/mm) were reduced by ALT-711. In the third experiment, 1-year-old SHR were given vehicle or ALT-711 (1 mg/kg/d) or placebo until natural death. After 3 months, ALT-711 markedly reduced urinary protein excretion (74.5 +/- 8.6 v 135.4 +/- 11.8 mg/24 h). Echocardiographic studies, performed at the outset and after 3 and 6 months, revealed two changed indexes. Left ventricular end-diastolic diameter increased more in control than in ALT rats, whereas E-wave deceleration time decreased more in control than in ALT rats. Therapy with ALT-711 exerted beneficial cardiovascular and renal effects in aged SHR, improving systolic pressure, left ventricular mass, geometry, and hydroxyproline content while reducing urinary protein excretion.

  7. Free-flow reabsorption of glucose, sodium, osmoles and water in rat proximal convoluted tubule.

    PubMed Central

    Bishop, J H; Green, R; Thomas, S

    1979-01-01

    1. Reabsorption of glucose, sodium, total solute (osmoles) and water in the rat proximal tubule (pars convoluta) were studied by free-flow micropuncture at normal (saline-infused), suppressed (saline with phlorizin) and elevated (glucose infusion) glucose reabsorption rates. 2. Phlorizin completely inhibited net glucose reabsorption, approximately halved reabsorption of sodium, total solutes and water, and reduced single nephron glomerular filtration rate (SNGFR). 3. In saline and glucose-infused groups, there were no significant differences between SNGFR nor between reabsorptions (fractional and absolute) of either sodium, total solute or water, which were uniformly distributed along segments assessible to micropuncture. 4. Glucose reabsorptive capacity existed along the entire pars convoluta, with highest reabsorptive rates in convolutions closest to the glomerulus (in saline-infused rats, 90% fractional reabsorption at 2 mm, over 95% at end pars convoluta; in glucose-infused rats, 55 and 90%, respectively). 5. In saline and glucose infused rats, a significant correlation existed between net glucose and sodium reabsorption, but the regression slopes differed and correlations became non-significant when the reabsorptive fluxes were factored by SNGFR. 6. For all groups, the majority of tubular fluid (TF) concentrations of osmoles and sodium were lower than those in plasma (over-all mean TFosm)Posm = 0.973 +/- 0.004, P less than 0.001; TFNa /PNa = 0.964 +/- 0.005, P less than 0.001). 7. Correspondingly, calculated osmolal and sodium concentrations in the reabsorbate were greater than those in plasma, and were significantly correlated with distance to puncture site with maximal values in the most proximal convolutions (for osmolality, approximately +79 m-osmole kg-1 water at 1 mm). PMID:469722

  8. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

    PubMed Central

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G.

    2016-01-01

    Background We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. Results We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Conclusions Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status. PMID:27132985

  9. Role of the renal sympathetic nerves in renal sodium/potassium handling and renal damage in spontaneously hypertensive rats

    PubMed Central

    Li, Jianling; He, Qiaoling; Wu, Weifeng; Li, Qingjie; Huang, Rongjie; Pan, Xiaofeng; Lai, Wenying

    2016-01-01

    Renal sympathetic nerve activity has an important role in renal disease-associated hypertension and in the modulation of fluid homeostasis. In the present study, changes in renal function and renal sodium/potassium handling were investigated in groups of 12-week-old male, spontaneously hypertensive rats with renal denervation (RDNX group) or sham denervation (sham group). The RDNX group excreted significantly more sodium than the sham group during the 2-week observation period (P<0.05). Following bilateral renal denervation, the fractional lithium excretion was elevated in the RDNX group compared with the sham group, but no significant effect was observed of renal denervation on the fractional distal reabsorption rate of sodium or the fractional excretion of potassium. Furthermore, the glomerular injury score and the wall-to-lumen ratio of the interlobular artery were significantly lower in the RDNX group than in the sham group (P<0.05). In conclusion, the present study indicates an involvement of the renal sympathetic nerves in the regulation of renal tubular sodium reabsorption in spontaneously hypertensive rats and in the renal damage associated with hypertension. PMID:27698757

  10. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    PubMed Central

    Zhu, Liye; Yu, Tao; Qi, Xiaozhe; Gao, Jing; Huang, Kunlun; He, Xiaoyun; Luo, Haoshu; Xu, Wentao

    2016-01-01

    Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD) and livers (SOD and GSH). DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model. PMID:27983637

  11. Zero-reabsorption doped-nanocrystal luminescent solar concentrators.

    PubMed

    Erickson, Christian S; Bradshaw, Liam R; McDowall, Stephen; Gilbertson, John D; Gamelin, Daniel R; Patrick, David L

    2014-04-22

    Optical concentration can lower the cost of solar energy conversion by reducing photovoltaic cell area and increasing photovoltaic efficiency. Luminescent solar concentrators offer an attractive approach to combined spectral and spatial concentration of both specular and diffuse light without tracking, but they have been plagued by luminophore self-absorption losses when employed on practical size scales. Here, we introduce doped semiconductor nanocrystals as a new class of phosphors for use in luminescent solar concentrators. In proof-of-concept experiments, visibly transparent, ultraviolet-selective luminescent solar concentrators have been prepared using colloidal Mn(2+)-doped ZnSe nanocrystals that show no luminescence reabsorption. Optical quantum efficiencies of 37% are measured, yielding a maximum projected energy concentration of ∼6× and flux gain for a-Si photovoltaics of 15.6 in the large-area limit, for the first time bounded not by luminophore self-absorption but by the transparency of the waveguide itself. Future directions in the use of colloidal doped nanocrystals as robust, processable spectrum-shifting phosphors for luminescent solar concentration on the large scales required for practical application of this technology are discussed.

  12. Characterization and reduction of reabsorption losses in luminescent solar concentrators.

    PubMed

    Wilson, Lindsay R; Rowan, Brenda C; Robertson, Neil; Moudam, Omar; Jones, Anita C; Richards, Bryce S

    2010-03-20

    The effects of excitation wavelength on the optical properties (emission spectrum and quantum yield) of a luminescent solar concentrator (LSC) containing a fluorescent organic dye (Lumogen F Rot 305) are studied. Excitation at wavelengths on the long-wavelength edge of the absorption spectrum of the dye results in redshifted emission, but the quantum yield remains constant at 100%. The origin of this effect and its consequences are discussed. The extent of the long-wavelength tail of the absorption spectrum of the dye is determined and the importance in reabsorption losses is shown. The optical efficiencies and photon transport probabilities of LSCs containing either an organic dye or a rare-earth lanthanide complex are compared using ray-tracing simulations and experiment. The optical efficiency is shown to depend strongly on the Stokes shift of the fluorophore. The lanthanide complex, which has a very large Stokes shift, exhibits a higher optical efficiency than the dye (64% cf. 50%), despite its lower quantum yield (86% cf. 100%).

  13. Observations on the mechanism and location of ascites reabsorption in man

    SciTech Connect

    Rector, W.G. Jr.; Ibarra, F.

    1987-04-01

    Animal data indicate that ascites is reabsorbed by a lymphatic mechanism and that these vessels are subdiaphragmatic in location. We evaluated the relative role of lymphatics in ascites reabsorption in man by comparing the ascites clearance and plasma appearance rates of intraperitoneally injected radiolabeled albumin to those of intraperitoneally injected labeled autologous red blood cells, which require, owing to their large size, lymphatic removal, in patients with cirrhosis and ascites. To evaluate the location of reabsorption, we repeated these measurements after replacing ascites in the subdiaphragmatic region with 500-1000 ml of intraperitoneally injected air, reasoning that this maneuver should slow or eliminate ascites reabsorption occurring at this site. We found that the transfer rates of albumin and red cells out of ascites were similar and that creation of pneumoperitoneum did not influence these rates. These data confirm that ascites protein reabsorption occurs via a lymphatic mechanism in man. They suggest, however, that these vessels may not be subdiaphragmatic in location.

  14. Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis.

    PubMed Central

    Santella, R N; Maddox, D A; Gennari, F J

    1991-01-01

    In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule (EP) is strongly dependent on delivery. Independent of delivery, metabolic acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated whether systemic pH changes induced by acute or chronic respiratory acid-base disorders also affect EP HCO3- reabsorption, independent of delivery (FLHCO3, filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h) and chronically (4-5 d) by increasing inspired PCO2. Hypocapnia was induced acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using hypoxemia to stimulate ventilation. When compared with normocapneic rats with similar FLHCO3, no stimulation of EP or overall proximal HCO3 reabsorption was found with either acute hypercapnia (PaCO2 = 74 mmHg, pH = 7.23) or chronic hypercapnia (PaCO2 = 84 mmHg, pH = 7.31). Acute hypocapnia (PaCO2 = 29 mmHg, pH = 7.56) did not suppress EP or overall HCO3 reabsorption. Chronic hypocapnia (PaCO2 = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was reversed when FLHCO3 was increased to levels comparable to euvolemic normocapneic rats. Thus, when delivery is accounted for, we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and, except at low delivery rates, no reduction in bicarbonate reabsorption in respiratory alkalosis. PMID:1991847

  15. Methylene blue solder re-absorption in microvascular anastomoses

    NASA Astrophysics Data System (ADS)

    Birch, Jeremy F.; Hepplewhite, J.; Frier, Malcolm; Bell, Peter R. F.

    2003-06-01

    Soldered vascular anastomoses have been reported using several chromophores but little is known of the optimal conditions for microvascular anastomosis. There are some indications of the optimal protein contents of a solder, and the effects of methylene blue on anastomotic strength. The effects of varying laser power density in vivo have also been described, showing a high rate of thrombosis with laser power over 22.9Wcm-2. However no evidence exists to describe how long the solder remains at the site of the anastomosis. Oz et al reported that the fibrin used in their study had been almost completely removed by 90 days but without objective evidence of solder removal. In order to address the issue of solder re-absorption from the site of an anastomosis we used radio-labelled albumin (I-125) incorporated into methylene blue based solder. This was investigated in both the situation of the patent and thrombosed anastomosis with anastomoses formed at high and low power. Iodine-125 (half life: 60.2 days) was covalently bonded to porcine albumin and mixed with the solder solution. Radio-iodine has been used over many years to determine protein turnover using either I-125 or I-131. Iodine-125 labelled human albumin is regularly used as a radiopharmaceutical tool for the determination of plasma volume. Radio-iodine has the advantages of not affecting protein metabolism and the label is rapidly excreted after metabolic breakdown. Labelling with chromium (Cr-51) causes protein denaturation and is lost from the protein with time. Labelled albumin has been reported in human studies over a 21-day period, with similar results reported by Matthews. Most significantly McFarlane reported a different rate of catabolism of I-131 and I-125 over a 22-day period. The conclusion from this is that the rate of iodine clearance is a good indicator of protein catabolism. In parallel with the surgery a series of blank standards were prepared with a known mass of solder to correct for isotope

  16. A light in the shadow: the use of Lucifer Yellow technique to demonstrate nectar reabsorption.

    PubMed

    Cardoso-Gustavson, Poliana; Robazzi Bignelli Valente Aguiar, João Marcelo; Ricardo Pansarin, Emerson; de Barros, Fábio

    2013-06-19

    Nectar reabsorption is a widely known phenomenon, related to the strategy of resource-recovery and also to maintain the nectar homeostasis at the nectary. The method currently performed to demonstrate nectar being reabsorbed involves the use of radioactive tracers applied to the nectary. Although this method works perfectly, it is complex and requires specific supplies and equipment. Therefore, here we propose an efficient method to obtain a visual demonstration of nectar reabsorption, adapting the use of Lucifer Yellow CH (LYCH), a fluorescent membrane-impermeable dye that can enter the vacuole by endocytosis. We applied a LYCH solution to the floral nectary (FN) of Cucurbita pepo L., which is a species known for its ability of nectar reabsorption, and to the extrafloral nectary (EFN) of Passiflora edulis Sims which does not reabsorb the secreted nectar. In all tests performed, we observed that LYCH stained the nectary tissues differentially according to the reabsorption ability of the nectary. The treated FN of C. pepo presented a concentrated fluorescence at the epidermis that decreased at the deeper nectary parenchyma, until reaching the vascular bundles, indicating nectar reabsorption in the flowers of the species. In contrast, treated EFN of P. edulis presented fluorescence only at the cuticle surface, indicating that nectar is not reabsorbed by that particular tissue. LYCH is an efficient marker to demonstrate nectar reabsorption.

  17. Water reabsorption capacity of the proximal convoluted tubule: a microperfusion study on rat kidney.

    PubMed Central

    Corman, B; Roinel, N; De Rouffignac, C

    1981-01-01

    1. The differences in the water reabsorption capacity observed from one proximal tubule to another were investigated in vivo by continuous microperfusion. 2. Two to seven loops were punctured along the same tubule. The [3H]inulin, 22Na, [14C]glucose, sodium, chloride and magnesium concentrations as well as the osmolality of the collected samples were studied as a function of the perfused length. 3. With Ringer bicarbonate solution perfused in Saclay Wistar rats, the water reabsorption capacity ranged from 0 to 3 nl . min-1 . mm-1 depending on the tubule. This reabsorption rate was closely correlated with the unidirectional reabsorption flux of sodium, and with the rise in tubular chloride and magnesium concentrations. 4. In Munich Wistar rats with glomeruli accessible at the kidney surface, tubule perfusion with a Ringer bicarbonate solution showed that the highest water reabsorption rates per mm of tubule were found for the perfusion sites closest to the glomerulus; water fluxes were also positively correlated with glucose transport. 5. In a second series of experiments on Saclay rats, perfusion of a Ringer solution containing a high chloride concentration (137 m-equiv/l.) was unable to increase the water reabsorption rate compared to the control perfusion; here again, water fluxes were positively correlated with glucose transport. PMID:7320874

  18. A light in the shadow: the use of Lucifer Yellow technique to demonstrate nectar reabsorption

    PubMed Central

    2013-01-01

    Background Nectar reabsorption is a widely known phenomenon, related to the strategy of resource-recovery and also to maintain the nectar homeostasis at the nectary. The method currently performed to demonstrate nectar being reabsorbed involves the use of radioactive tracers applied to the nectary. Although this method works perfectly, it is complex and requires specific supplies and equipment. Therefore, here we propose an efficient method to obtain a visual demonstration of nectar reabsorption, adapting the use of Lucifer Yellow CH (LYCH), a fluorescent membrane-impermeable dye that can enter the vacuole by endocytosis. Results We applied a LYCH solution to the floral nectary (FN) of Cucurbita pepo L., which is a species known for its ability of nectar reabsorption, and to the extrafloral nectary (EFN) of Passiflora edulis Sims which does not reabsorb the secreted nectar. In all tests performed, we observed that LYCH stained the nectary tissues differentially according to the reabsorption ability of the nectary. The treated FN of C. pepo presented a concentrated fluorescence at the epidermis that decreased at the deeper nectary parenchyma, until reaching the vascular bundles, indicating nectar reabsorption in the flowers of the species. In contrast, treated EFN of P. edulis presented fluorescence only at the cuticle surface, indicating that nectar is not reabsorbed by that particular tissue. Conclusion LYCH is an efficient marker to demonstrate nectar reabsorption. PMID:23783170

  19. Renal handling of fleroxacin in rabbits, dogs, and humans.

    PubMed Central

    Shiba, K; Saito, A; Shimada, J; Hori, S; Kaji, M; Miyahara, T; Kusajima, H; Kaneko, S; Saito, S; Ooie, T

    1990-01-01

    The renal handling of fleroxacin was studied by renal clearance and stop-flow techniques in rabbits and dogs and by analyzing the pharmacokinetics with and without probenecid in humans. In rabbits the excretion ratios (fleroxacin intrinsic renal clearance/glomerular filtration rate) were greater than unity (2.01) without probenecid and were decreased to a value below unity (0.680) with probenecid. In dogs, on the other hand, the excretion ratios were less than unity (0.608 and 0.456) both without and with probenecid, and so were not affected by probenecid. This fact suggested that fleroxacin was excreted into urine by both glomerular filtration and renal tubular secretion in rabbits, but only by glomerular filtration in dogs, accompanied by partial renal tubular reabsorption in both species; these mechanisms were also supported by stop-flow experiments. In humans probenecid treatment induced increases in the elimination half-life and area under the serum concentration-time curve and decreases in apparent serum clearance, renal clearance, and urinary recovery of fleroxacin. The excretion ratio without probenecid was 1.13, which was significantly decreased to 0.750 with probenecid. These results indicated that both renal tubular secretion and reabsorption contributed to renal excretion of fleroxacin in humans. The contribution of tubular secretion was species dependent and was extensive in rabbits, minimal in dogs, and moderate in humans. Renal tubular reabsorption was commonly found in every species. The long elimination half-life of fleroxacin in humans might be explained by its small total serum clearance and small renal clearance, which are attributed to less tubular secretion and more tubular reabsorption. PMID:2109576

  20. Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption.

    PubMed

    Pavlov, Tengis S; Levchenko, Vladislav; Staruschenko, Alexander

    2014-10-10

    The epithelial sodium channel (ENaC) is expressed in the aldosterone-sensitive distal nephron where it performs sodium reabsorption from the lumen. We have recently shown that ENaC activity contributes to the development of salt-induced hypertension as a result of deficiency of EGF level. Previous studies revealed that Rho GDP-dissociation inhibitor α (RhoGDIα) is involved in the control of salt-sensitive hypertension and renal injury via Rac1, which is one of the small GTPases activating ENaC. Here we investigated the intracellular mechanism mediating the involvement of the RhoGDIα/Rac1 axis in the control of ENaC and the effect of EGF on ENaC in this pathway. We demonstrated that RhoGDIα is highly expressed in the cortical collecting ducts of mice and rats, and its expression is down-regulated in Dahl salt-sensitive rats fed a high salt diet. Knockdown of RhoGDIα in cultured cortical collecting duct principal cells increased ENaC subunits expression and ENaC-mediated sodium reabsorption. Furthermore, RhoGDIα deficiency causes enhanced response to EGF treatment. Patch clamp analysis reveals that RhoGDIα significantly decreases ENaC current density and prevents its up-regulation by RhoA and Rac1. Inhibition of Rho kinase with Y27632 had no effects on ENaC response to EGF either in control or RhoGDIα knocked down cells. However, EGF treatment increased levels of active Rac1, which was further enhanced in RhoGDIα-deficient cells. We conclude that changes in the RhoGDIα-dependent pathway have a permissive role in the Rac1-mediated enhancement of ENaC activity observed in salt-induced hypertension.

  1. Taurine and the renal system

    PubMed Central

    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

  2. A photoactivatable probe for the Na+/H+ exchanger cross-links a 66-kDa renal brush border membrane protein

    SciTech Connect

    Ross, W.; Bertrand, W.; Morrison, A. )

    1990-04-05

    Earlier studies on LLC-PK1 cells have demonstrated two pharmacologically distinct Na+/H+ exchangers in renal epithelia. In addition, the cDNA clone for the human Na+/H+ antiporter which is growth factor activatable has been isolated and expressed. We report here the synthesis of an amiloride analogue that can be photoactivated and labeled with 125I. This analogue covalently cross-links a 66-kDa protein of bovine renal brush border membranes. A rabbit polyclonal antibody that was directed against a 20-amino acid peptide of the cytoplasmic domain of its human Na+/H+ antiporter also gives a positive Western against 66-kDa protein of bovine brush border membranes. Thus, the photoactive probe may be helpful in the isolation and purification of the brush border Na+/H+ exchanger.

  3. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

  4. Metabolism of 25-hydroxyvitamin D3 in renal slices from the X-linked hypophosphatemic (Hyp) mouse: abnormal response to fall in serum calcium.

    PubMed

    Tenenhouse, H S

    1984-02-01

    The effect of the X-linked Hyp mutation on 25-hydroxyvitamin D3 (25-OH-D3) metabolism in mouse renal cortical slices was investigated. Vitamin D replete normal mice and Hyp littermates fed the control diet synthesized primarily 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3); only minimal synthesis of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was detected in both genotypes and 1,25-(OH)2D3 formation was not significantly greater in Hyp mice relative to normal littermates, despite hypophosphatemia and hypocalcemia in the mutants. Calcium-deficient diet fed to normal mice reduced serum calcium (p less than 0.01), increased renal 25-hydroxyvitamin D3-1-hydroxylase (1-OHase) activity (p less than 0.05), and decreased 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) activity (p less than 0.05). In contrast, Hyp littermates on the calcium-deficient diet had decreased serum calcium (p less than 0.01), without significant changes in the renal metabolism of 25-OH-D3. Both normal and Hyp mice responded to the vitamin D-deficient diet with a fall in serum calcium (p less than 0.01), significantly increased renal 1-OHase, and significantly decreased renal 24-OHase activities. In Hyp mice, the fall in serum calcium on the vitamin D-deficient diet was significantly greater than that observed on the calcium-deficient diet. Therefore the ability of Hyp mice to increase renal 1-OHase activity when fed the vitamin D-deficient diet and their failure to do so on the calcium-deficient diet may be related to the resulting degree of hypocalcemia. The results suggest that although Hyp mice can respond to a disturbance of calcium homeostasis, the in vivo signal for the stimulation of renal 1-OHase activity may be set at a different threshold in the Hyp mouse; i.e. a lower serum calcium concentration is necessary for Hyp mice to initiate increased synthesis of 1,25(-OH)2D3.

  5. Reabsorption of ascites and the factors that affect this process in cirrhosis.

    PubMed

    Akay, Sinan; Ozutemiz, Omer; Kilic, Murat; Karasu, Zeki; Akyildiz, Murat; Karasulu, Ercument; Baka, Meral; Doganavsargil, Basak; Ersoz, Galip; Ulukaya, Sezgin; Alper, Isik; Ates, Utku; Batur, Yucel

    2008-10-01

    Ascites is one of the main features of liver decompensation in cirrhosis, and it is considered to be a dynamic process. In this study, we aimed to (1) measure the reabsorption rate of ascites; (2) evaluate whether these findings were related to features of ascites, hemodynamics, and serum measurements; and (3) examine morphologic changes in the diaphragm of cirrhotic patients. In all, 42 cirrhotic patients with ascites were enrolled in the study to comprise our study group. Using the dextran 70 test, patient ascites volumes and reabsorption rates were measured. Biopsies from the peritoneal side of the diaphragm were also processed for scanning electron microscopy and lymphatic immunohistochemical studies from the cirrhotic patients and control cadavers. The mean ascites reabsorption rate was 4.5 +/- 4.5 (0.18-14.6) mL/min, which correlated significantly with the calculated ascites volume (r = 0.75, P < 0.001). The mean ascites viscosity was 1.07 +/- 0.07 (0.99-1.17) centipoise, which demonstrated a high degree of negative correlation with the ascites reabsorption rate (r = -0.77, P < 0.001). Patients with a history of spontaneous bacterial peritonitis had significantly lesser ascites reabsorption rates than patients without this particular history. The size of lymphatic stomata in scanning electron microscopy depictions was increased, and lymphatic lacunae were dilated in immunohistochemical studies in the cirrhotic patients with ascites. However, these findings were not uniform in every cirrhotic patient with ascites. The volume and viscosity of ascites seem to influence its reabsorption rate. Additionally, previous episodes of spontaneous bacterial peritonitis may be responsible for the decreased ascites reabsorption rates observed in certain patient populations.

  6. Acute effects of ethanol on renal folate clearance in rats

    SciTech Connect

    Eisenga, B.H.; McMartin, K.E.

    1986-03-05

    Studies of the renal clearance of folic acid in primates demonstrate net reabsorption of folate by a saturable system. The acute administration of ethanol to rats causes a significant increase in urinary folate excretion. The mechanism for this effect is unknown and thus the effect of acute administration of ethanol on the renal absorption and urinary clearance of folate was studied in rats. Folic acid was administered to male Sprague-Dawley rats via continuous intravenous infusion in doses ranging from 3-75 micromoles/kg and renal clearance relative to inulin was determined. The effects of various dose levels of ethanol on these parameters were then determined. At a dose of 15 micromoles/kg, the renal clearance of folate relative to that of inulin was about 0.65 mg/min. At a plasma ethanol level about 100 mg/dl, the renal clearance of folate was not markedly altered. These results suggests that there is net reabsorption of folate in the rat kidney and that moderate doses of ethanol have little effect on renal effect on renal folate reabsorption.

  7. Extreme hypernatraemia in association with renal failure following caecocystoplasty.

    PubMed Central

    Walker, W. S.; Thurston, C. J.

    1984-01-01

    A case of extreme hypernatraemia (serum sodium 212 mmol/l) occurring in association with renal failure following a caecocystoplasty procedure is reported. The causative factors in extreme hypernatraemia are reviewed and an unusual reabsorptive mechanism via the transposed intestinal segment is proposed to explain the degree of hypernatraemia present in this case. PMID:6494095

  8. Osteomalacia associated with increased renal tubular resorption of phosphate (hypohyperparathyroidism)

    PubMed Central

    Kanis, J. A.; Walton, R. J.

    1976-01-01

    A 12-year-old girl, who presented with joint pains, was found to have hypocalcaemia, hyperphosphataemia due to increased renal tubular reabsorption, increased serum alkaline phosphatase activity, and osteomalacia. These features, which resemble those found in so-called hypohyperparathyroidism, were all rapidly reversed by small doses of cholecalciferol. PMID:183195

  9. The renal effects of SGLT2 inhibitors and a mini-review of the literature

    PubMed Central

    Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

    2016-01-01

    Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors’ efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors. PMID:28203358

  10. The renal effects of SGLT2 inhibitors and a mini-review of the literature.

    PubMed

    Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

    2016-12-01

    Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors' efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors.

  11. A model considering light reabsorption processes to correct in vivo chlorophyll fluorescence spectra in apples.

    PubMed

    Ramos, María E; Lagorio, María G

    2006-05-01

    Chlorophyll-a contained in the peel of Granny Smith apples emits fluorescence upon excitation with blue light. The observed emission, collected by an external detector and corrected by its spectral response, is still distorted by light reabsorption processes taking place in the fruit skin and differs appreciably from the true spectral distribution of fluorescence emerging from chlorophyll molecules in the biological tissue. Reabsorption processes particularly affect the ratio of fluorescence intensities at 680 nm and at 730 nm. A model to obtain the correct spectral distribution of the emission, from the experimental fluorescence recorded at a fluorometer detector and corrected for the detector spectral sensitivity, is developed in the present work. Measurements of the whole fruit reflectance, the peel transmittance and the flesh reflectance allow the calculation of the reabsorption-corrected spectra. The model is validated by comparing the corrected emission spectra with that obtained for a thin layer of apple-peel-chloroplasts, where no reabsorption takes place. It is recommended to correct distortions in emission spectra of intact fruits due to light reabsorption effects whenever a correlation between the physiological state of the fruit and its fluorescence spectra is investigated.

  12. Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury

    PubMed Central

    ZHANG, BAIYU; RONG, RONG; LI, HUIYAN; PENG, XUAN; XIONG, LIPING; WANG, YIHAN; YU, XUEQING; MAO, HAIPING

    2015-01-01

    X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic pathways at a post-mitochondrial level. XIAP functions by directly binding and inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low PI (DIABLO) is released into the cytosol, which results in displacement of XIAP from caspases. Heat shock protein 72 (HSP72), an anti-apoptotic protein, prevents mitochondrial injury resulting from acute renal ischemia/reperfusion (I/R), its role in Smac/DIABLO and XIAP signaling remains to be elucidated. In the present study, the hypothesis that HSP72 prevents XIAP degradation in vivo and in vitro was assessed. To this purpose, a rat model of I/R injury was used to investigate the renoprotective role of HSP72 by treatment with geranylgeranylacetone (GGA), a specific inducer of HSP72. The mechanism of the cytoprotective properties of HSP72 was also investigated in vitro using adenovirus-mediated overexpression of HSP72 in adenosine triphosphate (ATP)-depleted human kidney 2 (HK-2) cells. Pre-conditioning rats with GGA attenuated renal tubular cell damage, reduced cell apoptosis, preserved XIAP protein content and improved renal function following I/R injury. An in vitro study was performed in which cells were transiently exposed to 5 mM sodium cyanide in a glucose-free medium in order to induce apoptosis. Compared with the control, overexpression of HSP72 inhibited Smac/DIABLO release from the mitochondria and increased levels of XIAP and pro-caspase 3 in ATP-depleted HK-2 cells. In addition, HSP72 interacted with Smac/DIABLO. The present data demonstrates that HSP72 preserves renal function in I/R injury through its anti-apoptotic effects, which act by suppressing mitochondrial Smac/DIABLO release and preserving XIAP protein content. PMID:25394481

  13. Neural control of renal function.

    PubMed

    Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

    2011-04-01

    The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

  14. Fluorescence reabsorption calculation and influence on solid-state optical cooling.

    PubMed

    Wang, Xiaofeng; Chang, Shengli; Yang, Jiankun; Zhou, Mu; Cao, Dingxiang; Tan, Jichun

    2007-12-10

    The calculation model of fluorescence reabsorption and reemission with consideration of reflection on the boundary and material size using Monte Carlo method is proposed. To validate this stochastic model, experiments were conducted, and the calculated steady state spectra showed a good agreement with measurements. Using the absorption and fluorescence spectra of Yb-doped phosphate glass by careful measurements and corrections, we calculated the redshift in the observed fluorescence spectra and external quantum efficiency caused by fluorescence reabsorption and re-emission for the samples with the geometries of cylinder and cuboid. The calculation results show that the fluorescence reabsorption and re-emission have significant influence on the cooling efficiency. The calculation results also show that the cylinder with small waist beam incident (the incident light beam diameter is much less than the size of the sample, and goes through the center of the sample) is suitable for optical cooling.

  15. Depression of fractional sodium reabsorption by the proximal tubule of the dog without sodium diuresis

    PubMed Central

    Howards, Stuart S.; Davis, Bernard B.; Knox, Franklyn G.; Wright, Fred S.; Berliner, Robert W.

    1968-01-01

    The effect of infusions of hyperoncotic solutions on fractional sodium reabsorption by the proximal tubule of the dog was studied by the recollection micropuncture method. Tubule fluid to plasma inulin concentration ratios were measured for identified proximal tubule segments before and after infusion of 25% albumin or dextran solutions. Results were compared with changes in fractional reabsorption during saline diuresis. Plasma volume increased 66% ± SE 5.8 after infusion of albumin solution and 94% ± SE 8.2 after infusion of dextran solution. Fractional sodium reabosorption by the proximal tubule was depressed after infusion of both of these hyperoncotic solutions. Nevertheless, changes in sodium excretion after infusion of albumin and dextran were small. In contrast, after infusions of isotonic sodium chloride solution, which increased plasma volume 61% ± SE 5.8, a decrease in fractional reabsorption of 50.7% ± SE 7.2 was associated with large changes in sodium excretion. PMID:5658588

  16. An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats.

    PubMed Central

    Levine, D Z

    1985-01-01

    For many years it has been thought that distal nephron hydrogen ion secretion can be importantly modulated by factors such as sodium delivery, sodium avidity, and potassium stores. Free flow micropuncture studies have also indicated that the rate of bicarbonate delivery may also alter the rate of bicarbonate reabsorption. The present studies were undertaken to examine possible luminal influences on total CO2 reabsorption in microperfused distal tubules in the rat in vivo. Tubules from normal and acidotic rats were perfused with five solutions in a manner that induced changes in bicarbonate load, sodium and potassium fluxes (JNa, JK), and luminal sulfate concentration. in each collected perfusate, simultaneous analyses were undertaken to determine water reabsorption, Na, and K concentrations using graphite furnace atomic absorption spectroscopy and total CO2 by microcalorimetry. Using factorial analysis of covariance to account for confounding effects on total CO2 flux (JtCO2) such as water reabsorption, distal tubules of acidotic rats reabsorbed CO2 in the range of 50-112 pmol X min-1 X mm-1 X These JtCO2 values were not significantly correlated with HCO3 load, JNa, or JK despite changes in the latter from net reabsorption to net secretion. Distal tubules of rats with normal acid-base status had JtCO2 values which were neither significantly different from zero nor correlated with changes in JK and JNa. Further, doubling the load from 250-500 pmol/min (by doubling the perfusion rate of 25-mM HCO3 solutions) did not stimulate JtCO2 in these normal animals. Accordingly, these acute in vivo microperfusion studies indicate for the first time that neither load nor potassium or sodium fluxes are important modulators of distal tubule bicarbonate reabsorption. PMID:2982915

  17. Is nectar reabsorption restricted by the stalk cells of floral and extrafloral nectary trichomes?

    PubMed

    Cardoso-Gustavson, P; Davis, A R

    2015-01-01

    Reabsorption is a phase of nectar dynamics that occurs concurrently with secretion; it has been described in floral nectaries that exude nectar through stomata or unicellular trichomes, but has not yet been recorded in extrafloral glands. Apparently, nectar reabsorption does not occur in multicellular secretory trichomes (MST) due to the presence of lipophilic impregnations - which resemble Casparian strips - in the anticlinal walls of the stalk cells. It has been assumed that these impregnations restrict solute movement within MST to occur unidirectionally and exclusively by the symplast, thereby preventing nectar reflux toward the underlying nectary tissues. We hypothesised that reabsorption is absent in nectaries possessing MST. The fluorochrome lucifer yellow (LYCH) was applied to standing nectar of two floral and extrafloral glands of distantly related species, and then emission spectra from nectary sections were systematically analysed using confocal microscopy. Passive uptake of LYCH via the stalk cells to the nectary tissues occurred in all MST examined. Moreover, we present evidence of nectar reabsorption in extrafloral nectaries, demonstrating that LYCH passed the stalk cells of MST, although it did not reach the deepest nectary tissues. Identical (control) experiments performed with neutral red (NR) demonstrated no uptake of this stain by actively secreting MST, whereas diffusion of NR did occur in plasmolysed MST of floral nectaries at the post-secretory phase, indicating that nectar reabsorption by MST is governed by stalk cell physiology. Interestingly, non-secretory trichomes failed to reabsorb nectar. The role of various nectary components is discussed in relation to the control of nectar reabsorption by secretory trichomes. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  18. Occupational exposure to lead: effects on renal function

    SciTech Connect

    Hong, C.D.; Hanenson, I.B.; Lerner, S.; Hammond, P.B.; Pesce, A.J.; Pollak, V.E.

    1980-10-01

    Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.

  19. Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats.

    PubMed

    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. Role of claudins in renal calcium handling.

    PubMed

    Negri, Armando Luis

    2015-01-01

    Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline. Copyright © 2015 The Author. Published by Elsevier España, S.L.U. All rights reserved.

  1. Relation between BK-α/β4-mediated potassium secretion and ENaC-mediated sodium reabsorption.

    PubMed

    Wen, Donghai; Cornelius, Ryan J; Rivero-Hernandez, Dianelys; Yuan, Yang; Li, Huaqing; Weinstein, Alan M; Sansom, Steven C

    2014-07-01

    The large-conductance, calcium-activated BK-α/β4 potassium channel, localized to the intercalated cells of the distal nephron, mediates potassium secretion during high-potassium, alkaline diets. Here we determine whether BK-α/β4-mediated potassium transport is dependent on epithelial sodium channel (ENaC)-mediated sodium reabsorption. We maximized sodium-potassium exchange in the distal nephron by feeding mice a low-sodium, high-potassium diet. Wild-type and BK-β4 knockout mice were maintained on a low-sodium, high-potassium, alkaline diet or a low-sodium, high-potassium, acidic diet for 7-10 days. Wild-type mice maintained potassium homeostasis on the alkaline, but not acid, diet. BK-β4 knockout mice could not maintain potassium homeostasis on either diet. During the last 12 h of diet, wild-type mice on either a regular, alkaline, or an acid diet, or knockout mice on an alkaline diet, were administered amiloride (an ENaC inhibitor). Amiloride enhanced sodium excretion in all wild-type and knockout groups to similar values; however, amiloride diminished potassium excretion by 59% in wild-type but only by 33% in knockout mice on an alkaline diet. Similarly, amiloride decreased the trans-tubular potassium gradient by 68% in wild-type but only by 42% in knockout mice on an alkaline diet. Amiloride treatment equally enhanced sodium excretion and diminished potassium secretion in knockout mice on an alkaline diet and wild-type mice on an acid diet. Thus, the enhanced effect of amiloride on potassium secretion in wild-type compared to knockout mice on the alkaline diet clarify a BK- α/β4-mediated potassium secretory pathway in intercalated cells driven by ENaC-mediated sodium reabsorption linked to bicarbonate secretion.

  2. Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old

    PubMed Central

    Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio

    2012-01-01

    Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249

  3. Renal imaging techniques.

    PubMed

    Hierholzer, K; Hierholzer, J

    1997-01-01

    The ancient approach to obtain an image of the kidneys (and other internal organs) was 'section-inspection-imaging' by drawing, painting, sculpturing, and modelling. The present study follows chronologically the development and use of sectioning techniques from ancient (often forbidden) methods to modern microdissection and maceration of silicone-rubber-injected tubules. Inspection evolved from the use of the naked eye to magnifying lenses, microscopes and finally electron microscopy. Pertinent examples such as the description of the kidneys as the site of urine formation, the visualization of loop structures in the renal medulla and the imaging of tight junction strands are discussed. Inspection or visualization of renal structure and function has been revolutionized by modern noninvasive techniques, such as X-ray imaging, imaging by radioisotopes, ultrasound, computer tomography and nuclear magnetic resonance. Pertinent examples are given demonstrating the potency of the various techniques. The contribution of computerized data evaluation is discussed. The development of micropuncture and microperfusion techniques has opened the field for direct imaging not only of renal (sub)structural details but also of functional parameters such as transtubular reabsorption rates, single glomerular capillary filtration and conductance of the paracellular pathway. We focus particularly on techniques specifically designed to visualize renal hemodynamic and transport parameters.

  4. Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption.

    PubMed

    Hyodo, Susumu; Kakumura, Keigo; Takagi, Wataru; Hasegawa, Kumi; Yamaguchi, Yoko

    2014-12-15

    For adaptation to high-salinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na(+)/K(+)-ATPase, Na(+)-K(+)-Cl(-) cotransporters, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes.

  5. Effects of Reabsorption and Spatial Trap Distributions on the Radiative Quantum Efficiencies of ZnO

    DTIC Science & Technology

    2010-06-06

    in (a)] due to reabsorption, and the probability f reflesc of photon escape due to Fresnel reflection [derived from Eq. (1) and a Kramers- Kronig ...according to Eq. (1) using an index of refraction n(h̄ω) derived from a Kramers- Kronig transformation of the estimated absorption spectrum in Fig. 3(a

  6. Role of N-linked oligosaccharides in the transport activity of the Na+/H+ antiporter in rat renal brush-border membrane

    SciTech Connect

    Yusufi, A.N.; Szczepanska-Konkel, M.; Dousa, T.P.

    1988-09-25

    The role of N-linked oligosaccharide side chains in the biogenesis and function of Na+-coupled transporters in renal luminal brush-border membrane (BBM) is not known. We examined the question of how in vivo inhibition by alkaloid swainsonine of alpha-mannosidase, a key enzyme in processing of glycoproteins in the Golgi apparatus, affects Na+/H+ antiport and Na+/Pi symport as well as activities of other transporters and enzymes in rat renal BBM. Administration of swainsonine to thyroparathyroidectomized rats, control or treated with 3,5,3'-triiodothyronine, markedly decreased the rate of Na+/H+ antiport, but had no effect on the rate of Na+/Pi symport across renal BBM vesicles (BBMV). Moreover, administration of swainsonine did not change activities of Na+ gradient, ((extravesicular Na+) greater than (intravesicular Na+))-dependent transport of D-glucose, L-proline, or the amiloride-insensitive 22Na+ uptake by BBMV; the activities of the BBM enzymes alkaline phosphatase, gamma-glutamyltransferase, or leucine aminopeptidase in BBMV were also not changed. The in vitro enzymatic deglycosylation of BBM by incubating freshly isolated BBMV with bacterial endoglycosidase F also resulted in a decreased rate of Na+/H+ antiport, but not Na+-coupled symports of Pi, L-proline, and D-glucose, or the activities of the BBM enzymes were not significantly affected. Similar incubation with endoglycosidase H was without effect on any of these parameters. Both the modification of BBMV glycoproteins by administration fo swainsonine in vivo as well as the in vitro incubation of BBMV with endoglycosidase F resulted in a decrease of the apparent Vmax of Na+/H+ antiport, but did not change the apparent Km of this antiporter for extravesicular Na+ and did not increase H+ conductance of BBM.

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

    PubMed

    Blaine, Judith; Chonchol, Michel; Levi, Moshe

    2015-07-07

    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. Copyright © 2015 by the American Society of Nephrology.

  8. Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

    PubMed Central

    Chonchol, Michel; Levi, Moshe

    2015-01-01

    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. PMID:25287933

  9. Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney.

    PubMed Central

    Neumann, K H; Rector, F C

    1976-01-01

    The role of chloride concentration gradients in proximal NaCl and water reabsorption was examined in superficial proximal tubules of the rat by using perfusion and collection techniques. Reabsorptive rates (Jv), chloride concentrations, and transtubular potential difference were measured during perfusion with solutions (A) simulating an ultrafiltrate of plasma; (B) similar to (A) except that 20 meq/liter bicarbonate was replaced with acetate; (C) resembling late proximal fluid (glucose, amino acid, acetate-free, low bicarbonate, and high chloride); and (D) in which glucose and amino acids were replaced with raffinose and bicarbonate was partially replaced by poorly reabsorbable anions (cyclamate,sulfate, and methyl sulfate). In tubules perfused with solutions A and B, Jv were 2.17 and 2.7 nl mm-1 min-1 and chloride concentrations were 131.5 +/- 3.1 and 135 +/- 395 meq/liter, respectively, indicating that reabsorption is qualitatively similar to free-flow conditions and that acetate adequately replaces bicarbonate. With solution C, Jv was 2.10 nl mm-1 min-1 and potential difference was +1.5 +/- 0.2 mV, indicating that the combined presence of glucose, alanine, acetate, and bicarbonate per se is not an absolute requirement. Fluid reabsorption was virtually abolished when tubules were perfused with D solutions; Jv was not significantly different from zero despite sodium and chloride concentrations similar to plasma; chloride concentration was 110.8 +/- 0.2 meq/liter and potential difference was -0.98 mV indicating that chloride was close to electrochemical equilibrium. These results suggest the importance of the chloride gradient to proximal tubule reabsorption in regions where actively reabsorbable solutes (glucose, alanine, acetate, and bicarbonate) are lacking and provide further evidence for a passive model of NaCl and water transport. PMID:993334

  10. FGF23 regulates renal sodium handling and blood pressure.

    PubMed

    Andrukhova, Olena; Slavic, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E; Erben, Reinhold G

    2014-06-01

    Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na(+):Cl(-) co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (Na(+)) reabsorption and distal tubular membrane expression of NCC are reduced in mouse models of Fgf23 and αKlotho deficiency. Conversely, gain of FGF23 function by injection of wild-type mice with recombinant FGF23 or by elevated circulating levels of endogenous Fgf23 in Hyp mice increases distal tubular Na(+) uptake and membrane abundance of NCC, leading to volume expansion, hypertension, and heart hypertrophy in a αKlotho and dietary Na(+)-dependent fashion. The NCC inhibitor chlorothiazide abrogates FGF23-induced volume expansion and heart hypertrophy. Our findings suggest that FGF23 is a key regulator of renal Na(+) reabsorption and plasma volume, and may explain the association of FGF23 with cardiovascular risk in chronic kidney disease patients. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  11. FGF23 regulates renal sodium handling and blood pressure

    PubMed Central

    Andrukhova, Olena; Slavic, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E; Erben, Reinhold G

    2014-01-01

    Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na+:Cl− co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (Na+) reabsorption and distal tubular membrane expression of NCC are reduced in mouse models of Fgf23 and αKlotho deficiency. Conversely, gain of FGF23 function by injection of wild-type mice with recombinant FGF23 or by elevated circulating levels of endogenous Fgf23 in Hyp mice increases distal tubular Na+ uptake and membrane abundance of NCC, leading to volume expansion, hypertension, and heart hypertrophy in a αKlotho and dietary Na+-dependent fashion. The NCC inhibitor chlorothiazide abrogates FGF23-induced volume expansion and heart hypertrophy. Our findings suggest that FGF23 is a key regulator of renal Na+ reabsorption and plasma volume, and may explain the association of FGF23 with cardiovascular risk in chronic kidney disease patients. PMID:24797667

  12. Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region.

    PubMed

    Pruijm, Menno; Wuerzner, Grégoire; Maillard, Marc; Bovet, Pascal; Renaud, Claude; Bochud, Murielle; Burnier, Michel

    2010-07-01

    BACKGROUND. Glomerular hyperfiltration (GHF) is a well-recognized early renal alteration in diabetic patients. As the prevalence of GHF is largely unknown in populations in the African region with respect to normal fasting glucose (NFG), impaired fasting glucose (IFG) and type 2 diabetes [diabetes mellitus (DM)], we conducted a cross-sectional study in the Seychelles islands among families including at least one member with hypertension. METHODS. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and proximal tubular sodium reabsorption were measured using inulin, p-aminohippurate (PAH) and endogenous lithium clearance, respectively. Twenty-four-hour urine was collected on the preceding day. RESULTS. Of the 363 participants (mean age 44.7 years), 6.6% had IFG, 9.9% had DM and 63.3% had hypertension. The prevalence of GHF, defined as a GFR >140 ml/min, was 17.2%, 29.2% and 52.8% in NFG, IFG and DM, respectively (P trend <0.001). Compared to NFG, the adjusted odds ratio for GHF was 1.99 [95% confidence interval (CI) 0.73-5.44] for IFG and 5.88 (2.39-14.45) for DM. Lithium clearance and fractional excretion of lithium were lower in DM and IFG than NFG (P < 0.001). CONCLUSION. In this population of African descent, subjects with impaired fasting glucose or type 2 diabetes had a high prevalence of GHF and enhanced proximal sodium reabsorption. These findings provide further insight on the elevated incidence of nephropathy reported among African diabetic individuals.

  13. Theoretical and experimental study on reabsorption effect and temperature characteristic of a quasi-three-level 946nm Nd:YAG laser

    NASA Astrophysics Data System (ADS)

    Huang, Jing; Wan, Yuan; Chen, Weibiao

    2015-02-01

    The influence of temperature and incident pump power on reabsorption loss is theoretically discussed. Temperature characteristic and reabsorption loss rate of a diode-pumped quasi-three-level 946 nm Nd:YAG laser are investigated. Reabsorption effect has a significant impact on laser performance. The results indicate that reabsorption loss increases as the working temperature rises and decreases with the increased incident pump power.

  14. Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats.

    PubMed

    O'Neill, Julie; Fasching, Angelica; Pihl, Liselotte; Patinha, Daniela; Franzén, Stephanie; Palm, Fredrik

    2015-08-01

    Early stage diabetic nephropathy is characterized by glomerular hyperfiltration and reduced renal tissue Po2. Recent observations have indicated that increased tubular Na(+)-glucose linked transport (SGLT) plays a role in the development of diabetes-induced hyperfiltration. The aim of the present study was to determine how inhibition of SLGT impacts upon Po2 in the diabetic rat kidney. Diabetes was induced by streptozotocin in Sprague-Dawley rats 2 wk before experimentation. Renal hemodynamics, excretory function, and renal O2 homeostasis were measured in anesthetized control and diabetic rats during baseline and after acute SGLT inhibition using phlorizin (200 mg/kg ip). Baseline arterial pressure was similar in both groups and unaffected by SGLT inhibition. Diabetic animals displayed reduced baseline Po2 in both the cortex and medulla. SGLT inhibition improved cortical Po2 in the diabetic kidney, whereas it reduced medullary Po2 in both groups. SGLT inhibition reduced Na(+) transport efficiency [tubular Na(+) transport (TNa)/renal O2 consumption (Qo2)] in the control kidney, whereas the already reduced TNa/Qo2 in the diabetic kidney was unaffected by SGLT inhibition. In conclusion, these data demonstrate that when SGLT is inhibited, renal cortex Po2 in the diabetic rat kidney is normalized, which implies that increased proximal tubule transport contributes to the development of hypoxia in the diabetic kidney. The reduction in medullary Po2 in both control and diabetic kidneys during the inhibition of proximal Na(+) reabsorption suggests the redistribution of active Na(+) transport to less efficient nephron segments, such as the medullary thick ascending limb, which results in medullary hypoxia.

  15. The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome.

    PubMed

    Thethi, Tina; Kamiyama, Masumi; Kobori, Hiroyuki

    2012-04-01

    Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome.

  16. Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

    PubMed

    Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

    2015-06-01

    Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD.

  17. The Link Between the Renin-Angiotensin-Aldosterone System and Renal Injury in Obesity and the Metabolic Syndrome

    PubMed Central

    Thethi, Tina; Kamiyama, Masumi; Kobori, Hiroyuki

    2012-01-01

    Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome. PMID:22302531

  18. [Inherited tubular renal acidosis].

    PubMed

    Bouzidi, Hassan; Hayek, Donia; Nasr, Dhekra; Daudon, Michel; Fadhel Najjar, Mohamed

    2011-01-01

    Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

  19. Altered renal sodium handling and risk of incident hypertension: Results of the Olivetti Heart Study

    PubMed Central

    D’Elia, Lanfranco; Cappuccio, Francesco P.; Iacone, Roberto; Russo, Ornella; Galletti, Ferruccio; Strazzullo, Pasquale

    2017-01-01

    Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study). The study included 294 untreated normotensive non-diabetic men with normal renal function examined twice (1994–95 and 2002–04). Renal tubular Na handling was estimated by exogenous lithium clearance. Fractional reabsorption of Na in proximal and distal tubules was calculated and included in the analysis. At baseline, there was no association between BP and either proximal or distal fractional reabsorption of Na. At the end of the 8-year follow-up, direct associations were observed between baseline proximal (but not distal) Na fractional reabsorption and the changes occurred in systolic and diastolic BP over time (+2.79 and +1.53 mmHg, respectively, per 1SD difference in proximal Na-FR; p<0.01). Also multivariable analysis showed a direct association between baseline proximal Na fractional reabsorption and risk of incident hypertension, independently of potential confounders (OR: 1.34, 95%CI:1.06–1.70). The results of this prospective investigation strongly suggest a causal relationship between an enhanced rate of Na reabsorption in the proximal tubule and the risk of incident hypertension in initially normotensive men. PMID:28196131

  20. Red shift in the photoluminescence of colloidal carbon quantum dots induced by photon reabsorption

    NASA Astrophysics Data System (ADS)

    Zhang, Wenxia; Fan, Jiyang; Department of Physics, Southeast University, Nanjing 211189, People's Republic of China Team

    We synthesize the colloidal carbon/graphene quantum dots 1-9 nm in diameter through a novel alkaline-assisted method and deeply studied their photoluminescence properties. Surprisingly, the luminescence properties of a fixed collection of carbon dots can be systematically changed as the concentration varies. A model based on photon reabsorption is proposed which explains well the experiment. Infrared spectral study indicates that the surfaces of the carbon dots are totally terminated by three bonding-types of oxygen atoms, which result in their ultra-high hydrophilicity. Our result clarifies the mystery of distinct emission colors in carbon dots and indicates that photon reabsorption can strongly affect the luminescence properties of colloidal nanocrystals.This mechanism can be generalized to help understand the complex luminescence properties of other colloidal quantum dots. and should be seriously considered,otherwise, distinct conclusions may be drawn if different concentrations of quantum dots have been utilized in studying their luminescence properies.

  1. The role of reabsorption in the spectral distribution of phytoplankton fluorescence emission

    NASA Technical Reports Server (NTRS)

    Collins, D. J.; Mcdermid, I. S.; Kiefer, D. A.; Soohoo, J. B.

    1985-01-01

    A theoretical model has been developed to describe an experimentally observed spectral shift in the fluorescence emission from phytoplankton as a result of the internal reabsorption of that emission. This model accounts for both the absorption of the primary excitation and the modification of the fluorescence through the reabsorption of the emitted light by the chloroplast and by the surrounding medium. Comparisons are made between the results of the theoretical model and data derived from experiments using a number of different phytoplankton species, each adapted to varying light conditions. The details of the model are discussed, and the consequences of its interpretation on the spectral distribution of the fluorescence emission from phytoplankton are examined.

  2. Impact of Reabsorption on the Emission Spectra and Recombination Dynamics of Hybrid Perovskite Single Crystals.

    PubMed

    Diab, Hiba; Arnold, Christophe; Lédée, Ferdinand; Trippé-Allard, Gaëlle; Delport, Géraud; Vilar, Christèle; Bretenaker, Fabien; Barjon, Julien; Lauret, Jean-Sébastien; Deleporte, Emmanuelle; Garrot, Damien

    2017-07-06

    Understanding the surface properties of organic-inorganic lead-based perovskites is of high importance to improve the device's performance. Here, we have investigated the differences between surface and bulk optical properties of CH3NH3PbBr3 single crystals. Depth-resolved cathodoluminescence was used to probe the near-surface region on a depth of a few microns. In addition, we have studied the transmitted luminescence through thicknesses between 50 and 600 μm. In both experiments, the expected spectral shift due to the reabsorption effect has been precisely calculated. We demonstrate that reabsorption explains the important variations reported for the emission energy of single crystals. Single crystals are partially transparent to their own luminescence, and radiative transport is the dominant mechanism for propagation of the excitation in thick crystals. The transmitted luminescence dynamics are characterized by a long rise time and a lengthening of their decay due to photon recycling and light trapping.

  3. The role of reabsorption in the spectral distribution of phytoplankton fluorescence emission

    NASA Technical Reports Server (NTRS)

    Collins, D. J.; Mcdermid, I. S.; Kiefer, D. A.; Soohoo, J. B.

    1985-01-01

    A theoretical model has been developed to describe an experimentally observed spectral shift in the fluorescence emission from phytoplankton as a result of the internal reabsorption of that emission. This model accounts for both the absorption of the primary excitation and the modification of the fluorescence through the reabsorption of the emitted light by the chloroplast and by the surrounding medium. Comparisons are made between the results of the theoretical model and data derived from experiments using a number of different phytoplankton species, each adapted to varying light conditions. The details of the model are discussed, and the consequences of its interpretation on the spectral distribution of the fluorescence emission from phytoplankton are examined.

  4. Circulating biomarkers in renal cell carcinoma: the link between microRNAs and extracellular vesicles, where are we now?

    PubMed Central

    Teixeira, Ana L; Dias, Francisca; Gomes, Mónica; Fernandes, Mara

    2014-01-01

    Renal cell carcinoma (RCC) is a lethal urological cancer, with incidence and mortality rates increasing by 2-3% per decade. The lack of standard screening tests contributes to the fact that one-third of patients are diagnosed with locally invasive or metastatic disease. Moreover, 20-40% of RCC patients submitted to surgical nephrectomy will develop metastasis. MicroRNAs (miRNAs) are small non-coding RNAs responsible for gene regulation at a post-transcriptional level. It is accepted that they are deregulated in cancer and can influence tumor development. Thus, miRNAs are promising RCC biomarkers, since they can be detected using non-invasive methods. They are highly stable and easier to quantify in circulating biofluids. The elevated miRNA stability in circulating samples may be the consequence of their capacity to circulate inside of extracellular microvesicles (EMVs), for example, the exosomes. The EMVs are bilayered membrane vesicles secreted by all cell types. They can be released in the interstitial space or into circulating biofluids, which allows the travelling, binding and entrance of these vesicles in receptor cells. This type of cell communication can shuttle bioactive molecules between cells, allowing the horizontal transference of genetic material. In this review, we focus on circulating miRNAs (miR-210, miR-1233, miR-221, miR-15a, miR-451, miR-508, miR-378) in the biofluids of RCC patients and attempt to establish the diagnostic and prognostic accuracy, their synergic effects, and the pathways involved in RCC biology. PMID:28326253

  5. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition.

    PubMed

    DeFronzo, Ralph A; Norton, Luke; Abdul-Ghani, Muhammad

    2017-01-01

    The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, however, with new studies demonstrating that inhibition of renal glucose reabsorption reduces blood pressure, ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. In this Review we examine the role of SGLT2 and SGLT1 in the regulation of renal glucose reabsorption in health and disease and the effect of SGLT2 inhibition on renal function, glucose homeostasis, and cardiovascular disease.

  6. The effects of anions on fluid reabsorption from the proximal convoluted tubule of the rat.

    PubMed Central

    Green, R; Greenwood, S L; White, S

    1988-01-01

    1. Fluid reabsorption from surface proximal tubules of the rat was measured in vivo using stationary microperfusion techniques. Reabsorptive rate (Jv) was measured from droplets containing chloride as the main reabsorbable anion and when chloride was substituted by bromide, iodide, nitrate, acetate, isethionate or methylsulphate in either the tubular lumen alone or in both lumen and peritubular capillaries. 2. In tubules with an intact blood supply, droplet volume decreased in a manner best described by a single exponential and substitution of chloride by nitrate or bromide had no effect on Jv. Substitution by iodide or acetate inhibited Jv by approximately 17% but substitution by methylsulphate or isethionate caused droplets to transiently increase in volume before shrinkage which was itself inhibited by approximately 50%. The inhibitory action of isethionate was found to be concentration dependent. 3. Recollection and analysis of droplets which were initially free of chloride, containing either nitrate or isethionate, showed that chloride entered these droplets, but that the initial rate of chloride entry was greater for nitrate than isethionate droplets. 4. When tubules and capillaries were perfused with chloride solutions containing no bicarbonate, Jv was reduced to about 20% of the value when peritubular capillary blood flow was intact. Substituting chloride in the tubular and capillary perfusion revealed a sequence for supporting fluid reabsorption that was identical to that when chloride was substituted in tubule fluid alone: bromide = nitrate greater than iodide = acetate greater than isethionate. Addition of 2.0 mmol l-1 NaCN reduced the reabsorptive flux to zero. 5. The results of this study are consistent with transcellular transport of anions across the proximal tubular epithelium. The pathways for anion transport are likely to involve a series of non-selective mechanisms such as anion exchangers. PMID:3256612

  7. The Association of Albuminuria With Tubular Reabsorption of Uric Acid: Results From a General Population Cohort

    PubMed Central

    Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.

    2014-01-01

    Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow‐up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520

  8. Nonsaturable amino acid reabsorption in kidneys of normal and mercury-poisoned rabbits

    SciTech Connect

    Foulkes, E.C.; Blanck, S. )

    1988-11-01

    At high plasma concentrations, a high-capacity, low-affinity or nonsaturable flux (J{sub hc}) accounts for a residual fractional reabsorption of cycloleucine, aspartate, and AIB of approximately 50% of the filtered load in rabbits; J{sub hc} in micromoles per milliliter glomerular filtrate is reduced in Hg-poisoned animals. The nonsaturable flux of cycloleucine is characterized by a transepithelial transit time (TET) of approximately 2 min in control animals; it was consistently much longer in Hg-poisoned animals. The clearance ratio of creatinine/inulin averaged 1.0, and no J{sub hc} could be demonstrated for glucose. We conclude that J{sub hc} is a high-capacity, low-affinity amino acid flux which passes through an intracellular solute pool, and which is sensitive to Hg at both the brush border and the basolateral cell membrane. If calculation of the saturation constants of aspartate reabsorption is restricted to experiments in which U/P <1.0, i.e. where J{sub hc} is unlikely too contribute greatly to reabsorption, values some 20% lower than those previously reported are obtained; the Hg inhibition still is apparently uncompetitive in nature.

  9. Effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans.

    PubMed

    Shamsuddin, A K M; Kuwahara, T; Oue, A; Nomura, C; Koga, S; Inoue, Y; Kondo, N

    2005-07-01

    The effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans is unknown. In this study, eight healthy subjects performed a 60-min cycling exercise at a constant intensity (60% VO(2max)) under moderate (25 degrees C) and cool (15 degrees C) ambient temperatures at a constant relative humidity of 40%. The sweating rate (SR), index of sweat ion concentration (ISIC) by using sweat conductivity, esophageal temperature (Tes), mean skin temperature, and heart rate (HR) were measured continuously under both ambient temperatures. The SR and ISIC were significantly lower at the cool ambient temperature versus the moderate temperature. There were no significant differences in the changes in HR and esophageal temperature between these ambient temperature conditions, while the mean skin temperature was significantly lower at the cool ambient temperature by almost 3 degrees C (P < 0.05). The slopes of the relationships between Tes and the SR and ISIC were significantly lower and the thresholds of these relationships were significantly higher at the cool ambient temperature (P < 0.05). The ion reabsorption capacity of the sweat glands was significantly lower (P < 0.05) in a cool environment (0.21 +/- 0.04 vs. 0.52 +/- 0.06 mg/cm(2)/min at 15 and 25 degrees C, respectively) as evaluated using the relationships for SR and ISIC. The results suggest that the ion reabsorption capacity of the sweat glands is influenced by skin temperature during exercise in humans.

  10. Correlation between fluid reabsorption and proximal tubule ultrastructure during development of the rat kidney.

    PubMed

    Aperia, A; Larsson, L

    1979-01-01

    Parallel functional and ultrastructural studies were performed in maturing rats in order to elucidate factors determining the development of proximal tubular fluid reabsorption. Three groups of hydropenic animals, which were 22 to 24, 28 to 32 and 40 to 45 days old, were studied. Nephron function was evaluated at the single nephron level by micropuncture technique. The ultrastructure of the developing proximal tubules was analysed by morphometric techniques following fixation of single nephrons. Kidney weight, proximal convoluted tubule length and diameter increased during postnatal development. SNGFR increased from 2.98 to 8.57 and to 20.5 nl/min in respective group of rats whereas proximal tubular fluid reabsorption Jv (a) increased from 0.15 to 0.22 and 0.34 micron3.micron-2.s-1. Parallel to the functional development the relative area of lateral and basal cell membrane increased, resulting in a constant relationship between net fluid reabsorption and the lateral and basal cell membrane area during the fourth postnatal week and then only a slight increase in this relation during the further development. The results suggest that net fluid transport during hydropenia is determined by the amount of available lateral and basal cell membranes where the transporting enzyme for sodium is located.

  11. Synthesis of Reabsorption-Suppressed Type-II/Type-I ZnSe/CdS/ZnS Core/Shell Quantum Dots and Their Application for Immunosorbent Assay.

    PubMed

    Wang, Sheng; Li, Jin Jie; Lv, Yanbing; Wu, Ruili; Xing, Ming; Shen, Huaibin; Wang, Hongzhe; Li, Lin Song; Chen, Xia

    2017-12-01

    We report a phosphine-free one-pot method to synthesize ZnSe/CdS/ZnS core-shell quantum dots (QDs) with composite type-II/type-I structures and consequent reabsorption suppression properties. The as-synthesized QDs possess high efficient red emission (with quantum yield of 82%) and high optical stability. Compared to type-I QDs, the ZnSe/CdS/ZnS QDs show larger Stokes shift and lower reabsorption which can reduce the emission loss and improve the level of fluorescence output. The ZnSe/CdS/ZnS QDs are used as fluorescent labels to exploit their application in fluorescence-linked immunosorbent assay (FLISA) for the first time in the detection of C-reactive protein (CRP) with a limit of detection (LOD) of 0.85 ng/mL, which is more sensitive than that of CdSe/ZnS type-I QDs based FLISA (1.00 ng/mL). The results indicate that the ZnSe/CdS/ZnS type-II/type-I QDs may be good candidates for applications in biomedical information detection.

  12. Synthesis of Reabsorption-Suppressed Type-II/Type-I ZnSe/CdS/ZnS Core/Shell Quantum Dots and Their Application for Immunosorbent Assay

    NASA Astrophysics Data System (ADS)

    Wang, Sheng; Li, Jin Jie; Lv, Yanbing; Wu, Ruili; Xing, Ming; Shen, Huaibin; Wang, Hongzhe; Li, Lin Song; Chen, Xia

    2017-06-01

    We report a phosphine-free one-pot method to synthesize ZnSe/CdS/ZnS core-shell quantum dots (QDs) with composite type-II/type-I structures and consequent reabsorption suppression properties. The as-synthesized QDs possess high efficient red emission (with quantum yield of 82%) and high optical stability. Compared to type-I QDs, the ZnSe/CdS/ZnS QDs show larger Stokes shift and lower reabsorption which can reduce the emission loss and improve the level of fluorescence output. The ZnSe/CdS/ZnS QDs are used as fluorescent labels to exploit their application in fluorescence-linked immunosorbent assay (FLISA) for the first time in the detection of C-reactive protein (CRP) with a limit of detection (LOD) of 0.85 ng/mL, which is more sensitive than that of CdSe/ZnS type-I QDs based FLISA (1.00 ng/mL). The results indicate that the ZnSe/CdS/ZnS type-II/type-I QDs may be good candidates for applications in biomedical information detection.

  13. Development of bioartificial renal tubule devices with lifespan-extended human renal proximal tubular epithelial cells.

    PubMed

    Sanechika, Noriyuki; Sawada, Kaichiro; Usui, Yukio; Hanai, Kazuya; Kakuta, Takatoshi; Suzuki, Hajime; Kanai, Genta; Fujimura, Satoshi; Yokoyama, Tun Aung; Fukagawa, Masafumi; Terachi, Toshiro; Saito, Akira

    2011-09-01

    The bioartificial renal tubule device is a cell therapy system for renal failure. The major obstacle in the development of the bioartificial renal tubule device is the obtainment of a large number of viable renal tubule cells to seed on the inner surface of hollow fibers. Although our previous studies had used a transformed cell line, they may be dangerous for clinical uses. Therefore, different approaches to amplify renal proximal tubular epithelial cells (RPTEC) in culture without oncogenes, vectors and carcinogens have been required. The limitation of the replicative lifespan of human RPTEC, which is ∼12 population doublings (PDs), was extended by invalidating messenger RNA of cell cycle-related genes with antisense oligonucleotide or small interfering RNA (siRNA). Periodic transfection of siRNA to a tumor suppressor p53 or a cyclin-dependent kinase inhibitor p16(INK4a) extended the lifespan by 33 and 63 PDs, respectively, in 3 months of culture. The siRNA-mediated lifespan extension was controllable because cell division ceased within 2 weeks after the transfection was discontinued. Expressions of γ-glutamyltransferase 1 and glucose transporter 1 were recovered in siRNA-transfected RPTEC cultured on porous membranes. Bioartificial renal tubule devices (0.8 m(2)) constructed with these cells showed reabsorption of water (122.3 ± 4.2 mL/30 min), sodium (18.1 ± 0.7 mEq/30 min) and glucose (121.7 ± 4.4 mg/30 min) after 1 week of circulation. Furthermore, β2-microglobulin and pentosidine were metabolized by RPTEC in mini-devices (65 cm(2)) within 48 h of circulation. These approaches enabled us to yield a high enough number of RPTEC for construction of bioartificial renal tubule devices repeatedly. Lifespan-extended RPTEC could recover their specific characteristics by culturing on porous membranes, and bioartificial renal tubule devices constructed with these cells showed good performances of reabsorption and metabolism. A large number of human renal tubular

  14. Circadian regulation of renal function.

    PubMed

    Firsov, Dmitri; Bonny, Olivier

    2010-10-01

    Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms.

  15. The lipid composition of high-density lipoprotein affects its re-absorption in the kidney by proximal tubule epithelial cells.

    PubMed Central

    Breznan, Dalibor; Veereswaran, Vasanthi; Viau, France J; Neville, Tracey A-M; Sparks, Daniel L

    2004-01-01

    The kidney is believed to play a major role in the clearance of apoA-I (apolipoprotein A-I) and HDL (high-density lipoprotein) particles from the bloodstream. Proximal tubule epithelial cells of the kidney appear to prevent the loss of these proteins in the urine by re-absorbing them from the urinary filtrate. Experiments were undertaken to investigate the factors that regulate the renal re-absorption of apoA-I and small HDL in a transformed human proximal tubule epithelial (HKC-8) cell line. Fluorescent microscopic studies show that HKC-8 cells can readily bind and take up HDL particles. Intracellular localization of fluorescently labelled native HDL shows its accumulation in endocytotic vesicles, in a perinuclear region after 1 h. Binding studies reveal a saturable cell association of (125)I-HDL with the HKC-8 cell surface after 2 h. HKC-8 cells do not degrade apoA-I or other HDL-apoproteins. The specific cell association of lipid-free apoA-I is approx. 2-fold less than that observed for native HDL. Similarly, reconstituted HDL prepared from HDL-apoproteins and pure phospholipids also exhibits a low cell association with the HKC-8 cells. In contrast, reconstituted HDL prepared with the extracted lipids of HDL and pure apoA-I exhibits an even higher cell association than that observed with the native lipoprotein. A detailed characterization of the major lipid classes in reconstituted HDL shows that only cholesteryl ester increases the cell association of the recombinant particles. These results show that the cholesteryl ester content of HDL may play an important role in the re-absorptive salvage of HDL by the proximal tubule cells of the kidney. PMID:14711371

  16. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling

    PubMed Central

    Chaki, Moumita; Airik, Rannar; Ghosh, Amiya K.; Giles, Rachel H.; Chen, Rui; Slaats, Gisela G.; Wang, Hui; Hurd, Toby W.; Zhou, Weibin; Cluckey, Andrew; Gee, Heon-Yung; Ramaswami, Gokul; Hong, Chen-Jei; Hamilton, Bruce A.; Červenka, Igor; Ganji, Ranjani Sri; Bryja, Vitezslav; Arts, Heleen H.; van Reeuwijk, Jeroen; Oud, Machteld M.; Letteboer, Stef J.F.; Roepman, Ronald; Husson, Hervé; Ibraghimov-Beskrovnaya, Oxana; Ysunaga, Takayuki; Walz, Gerd; Eley, Lorraine; Sayer, John A.; Schermer, Bernhard; Liebau, Max C.; Benzing, Thomas; Le Corre, Stephanie; Drummond, Iain; Joles, Jaap A.; Janssen, Sabine; Allen, Susan J.; Natarajan, Sivakumar; O Toole, John F.; Attanasio, Massimo; Saunier, Sophie; Antignac, Corinne; Koenekoop, Robert K.; Ren, Huanan; Lopez, Irma; Nayir, Ahmet; Stoetzel, Corinne; Dollfus, Helene; Massoudi, Rustin; Gleeson, Joseph G.; Andreoli, Sharon P.; Doherty, Dan G.; Lindstrad, Anna; Golzio, Christelle; Katsanis, Nicholas; Pape, Lars; Abboud, Emad B.; Al-Rajhi, Ali A.; Lewis, Richard A.; Lupski, James R.; Omran, Heymut; Lee, Eva; Wang, Shaohui; Sekiguchi, JoAnn M.; Saunders, Rudel; Johnson, Colin A.; Garner, Elizabeth; Vanselow, Katja; Andersen, Jens S.; Shlomai, Joseph; Nurnberg, Gudrun; Nurnberg, Peter; Levy, Shawn; Smogorzewska, Agata; Otto, Edgar A.; Hildebrandt, Friedhelm

    2012-01-01

    SUMMARY Nephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive diseases that affect kidney, retina and brain. Genetic defects in NPHP gene products that localize to cilia and centrosomes defined them as ‘ciliopathies’. However, disease mechanisms remain poorly understood. Here we identify by whole exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC. All three genes function within the DNA damage response (DDR) pathway, hitherto not implicated in ciliopathies. We demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164 and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents, and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype. We identify TTBK2, CCDC92, NPHP3 and DVL3 as novel CEP164 interaction partners. Our findings link degenerative diseases of kidney and retina, disorders of increasing prevalence, to mechanisms of DDR. PMID:22863007

  17. A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation.

    PubMed

    Lah, Melissa; Niranjan, Tejasvi; Srikanth, Sujata; Holloway, Lynda; Schwartz, Charles E; Wang, Tao; Weaver, David D

    2016-04-01

    We further evaluated a previously reported family with an apparently undescribed X-linked syndrome involving joint contractures, keloids, an increased optic cup-to-disc ratio, and renal stones to elucidate the genetic cause. To do this, we obtained medical histories and performed physical examination on 14 individuals in the family, five of whom are affected males and three are obligate carrier females. Linkage analysis was performed on all but one individual and chromosome X-exome sequencing was done on two affected males. The analysis localized the putative gene to Xq27-qter and chromosome X-exome sequencing revealed a mutation in exon 28 (c.4726G>A) of the filamin A (FLNA) gene, predicting that a conserved glycine had been replaced by arginine at amino acid 1576 (p.G1576R). Segregation analysis demonstrated that all known carrier females tested were heterozygous (G/A), all affected males were hemizygous for the mutation (A allele) and all normal males were hemizygous for the normal G allele. The data and the bioinformatic analysis indicate that the G1576R mutation in the FLNA gene is very likely pathogenic in this family. The syndrome affecting the family shares phenotypic overlap with other syndromes caused by FLNA mutations, but appears to be a distinct phenotype, likely representing a unique genetic syndrome. © 2016 Wiley Periodicals, Inc.

  18. Renal response to environmental toxics

    PubMed Central

    Finn, William F.

    1977-01-01

    Several characteristics of normal renal function increase the risk to the kidney of damage by environmental toxins. Due to the magnitude of renal blood flow the total amount of noxious substance delivered may be disproportionately high. Furthermore, the capacity to concentrate substances within the kidney by processes of filtration, reabsorption and secretion has the potential to increase the toxicity of agents which would otherwise not lead to tissue injury. Unfortunately, there are few tests of renal function which are able to detect early functional abnormalities and which, at the same time, are suited for screening purposes by virtue of their simplicity, cost and safety. Furthermore, interpretation of the tests is complicated by adaptive changes in renal function which occur with aging and in response to other disease processes. Environmental agents produce a wide spectrum of renal dysfunction. Acute renal damage follows exposure to glycols, organic solvents, heavy metals, diagnostic and therapeutic agents and a variety of miscellaneous substances. Chronic renal disease may take the form of isolated tubular defects as seen with cadmium, interstitial nephritis due to the ingestion of lead, or vascular damage induced by external radiation. Some forms of glomerulonephritis may also be related to environmental toxins as are certain tumors of the urinary tract. In a somewhat different fashion, patients whose renal function is limited by the presence of pre-existing disease may manifest toxicity from substances ordinarily excreted in the urine. Particular problems exist with the patients on dialysis, as they are at considerable risk to alterations in the environment. PMID:598348

  19. Renal disposition of colistin in the isolated perfused rat kidney.

    PubMed

    Ma, Zheng; Wang, Jiping; Nation, Roger L; Li, Jian; Turnidge, John D; Coulthard, Kingsley; Milne, Robert W

    2009-07-01

    Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

  20. Activation of the epithelial Na+ channel in the collecting duct by vasopressin contributes to water reabsorption.

    PubMed

    Bugaj, Vladislav; Pochynyuk, Oleh; Stockand, James D

    2009-11-01

    We used patch-clamp electrophysiology on isolated, split-open murine collecting ducts (CD) to test the hypothesis that regulation of epithelial sodium channel (ENaC) activity is a physiologically important effect of vasopressin. Surprisingly, this has not been tested directly before. We ask whether vasopressin affects ENaC activity distinguishing between acute and chronic effects, as well as, parsing the cellular signaling pathway and molecular mechanism of regulation. In addition, we quantified possible synergistic regulation of ENaC by vasopressin and aldosterone associating this with a requirement for distal nephron Na+ reabsorption during water conservation vs. maintenance of Na+ balance. We find that vasopressin significantly increases ENaC activity within 2-3 min by increasing open probability (P(o)). This activation was dependent on adenylyl cyclase (AC) and PKA. Water restriction (18-24 h) and pretreatment of isolated CD with vasopressin (approximately 30 min) resulted in a similar increase in P(o). In addition, this also increased the number (N) of active ENaC in the apical membrane. Similar to P(o), increases in N were sensitive to inhibitors of AC. Stressing animals with water and salt restriction separately and jointly revealed an important effect of vasopressin: conservation of water and Na+ each independently increased ENaC activity and jointly had a synergistic effect on channel activity. These results demonstrate a quantitatively important action of vasopressin on ENaC suggesting that distal nephron Na+ reabsorption mediated by this channel contributes to maintenance of water reabsorption. In addition, our results support that the combined actions of vasopressin and aldosterone are required to achieve maximally activated ENaC.

  1. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.

    PubMed

    Shigematsu, Takashi; Kazama, Junichiro James; Yamashita, Takeyoshi; Fukumoto, Seiji; Hosoya, Tatsuo; Gejyo, Fumitake; Fukagawa, Masafumi

    2004-08-01

    Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001). Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.

  2. Genetics Home Reference: action myoclonus-renal failure syndrome

    MedlinePlus

    ... Management Genetic Testing (1 link) Genetic Testing Registry: Epilepsy, progressive myoclonic 4, with or without renal failure ... failure syndrome action myoclonus–renal failure syndrome AMRF epilepsy, progressive myoclonic 4, with or without renal failure ...

  3. Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study.

    PubMed

    Tomai, Fabrizio; Ribichini, Flavio; De Luca, Leonardo; Petrolini, Alessandro; Ghini, Anna S; Weltert, Luca; Spaccarotella, Carmen; Proietti, Igino; Trani, Carlo; Nudi, Francesco; Pighi, Michele; Vassanelli, Corrado

    2014-03-11

    Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the rate of target vessel revascularization in comparison with bare-metal stents (BMS) in patients with chronic kidney disease. However, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess. Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease (estimated glomerular filtration rate <60 mL/min). The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months. In 215 patients, 512 coronary vessels were successfully treated with the randomly assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7% (95% confidence interval, 1.1%-5.6%) and 11.4% (95% confidence interval, 7.8% to 16%), respectively, P<0.001. For the multivariate analysis, independent predictors of the ischemia-driven target vessel revascularization were BMS implantation (odds ratio, 4.95; 95% confidence interval, 2.1-11.6; P<0.001) and vessel size (odds ratio, 0.32; 95% confidence interval, 0.1-0.7; P=0.006). This is the first randomized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design, in patients who have chronic kidney disease with multivessel coronary artery disease. http

  4. Does High Alveolar Fluid Reabsorption Prevent HAPE in Individuals with Exaggerated Pulmonary Hypertension in Hypoxia?

    PubMed

    Betz, Theresa; Dehnert, Christoph; Bärtsch, Peter; Schommer, Kai; Mairbäurl, Heimo

    2015-12-01

    An exaggerated increase in pulmonary arterial systolic pressure (PAsP) is a highlight of high altitude pulmonary edema (HAPE). However, the incidence of HAPE at 4559 m was much lower in altitude-naïve individuals with exaggerated pulmonary vasoconstriction (HPV) in normobaric hypoxia than in known HAPE-susceptibles, indicating that elevated PAsP alone is insufficient to induce HAPE. A decreased nasal potential difference (NPD) has been found in HAPE-susceptibles, where, based on animal models, NPD serves as surrogate of alveolar epithelial ion transport. We hypothesize that those HAPE-resistant individuals with high HPV may be protected by elevated alveolar Na and fluid reabsorption, which might be detected as increased NPD. To test this hypothesis, we measured NPD in normoxia of subjects who were phenotyped in previous studies as high altitude tolerant (controls), known HAPE-susceptibles with high HPV (HP+HAPE), as well as individuals with high HPV but without HAPE (HP-no-HAPE) at 4559 m. NPD and amiloride-sensitive NPD were lower in HP+HAPE than in controls, whereas HP-no-HAPE were not different from either group. There were no differences in Cl-transport between groups. Our results show low nasal ion transport in HAPE but higher transport in those individuals with the highest HPV but without HAPE. This indicates that in some individuals with high PAsP at high altitude high alveolar fluid reabsorption might protect them from HAPE.

  5. The discovery of the synovial lymphatic stomata and lymphatic reabsorption in knee effusion.

    PubMed

    Ping, Zepeng; Jiang, Tingting; Wang, Chong; Chen, Zhongyi; Chen, Zhongliang; Wang, Jiaxiong; Wang, Li; Wang, Beibei; Xu, Dandan; Liu, Changming; Li, Zhongjie; Li, Ji-Cheng

    2015-06-01

    To illustrate the mechanism of lymphatic reabsorption in knee joint effusion. The current investigation employed transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques to reveal the ultrastructure of the knee synovial membrane in New Zealand rabbits and human. Ultrastructural changes of the synovial lymphatic stomata were observed by using trypan blue absorption and sodium hydroxide (NaOH) digestion methods, and the animal models of synovitis. New Zealand rabbits and human synovial membranes were composed of two types of synovial cells: type A and type B. No lymphatic stomata were found among type A synovial cells, whereas lymphatic stomata with the diameters ranging 0.74-3.26 µm were found in type B synovial cells, and some stomata were closed. After the NaOH digestion, a number of sieve pores, similar to lymphatic stomata in size and shape, were observed in the dense fibrous connective tissue underneath the type B synovial cells. After injecting trypan blue into the rabbit knee joint cavity, absorption of trypan blue through the lymphatic stomata was observed, suggesting the absorption function of the synovial lymphatic stomata. In the rabbit knee joint synovitis models, the synovial lymphatic stomata diameter enlarged. Some macrophages migrated from the lymphatic stomata, indicating that the synovial lymphatic stomata were involved in the joint effusion absorption and inflammatory response. Our study is the first to report the existence of synovial lymphatic stomata in the New Zealand rabbits and human knee joints. Lymphatic stomata may have an important role in the reabsorption of joint effusion.

  6. Reduced Renal Calcium Excretion in the Absence of Sclerostin Expression: Evidence for a Novel Calcium-Regulating Bone Kidney Axis

    PubMed Central

    Vallon, Volker

    2014-01-01

    The kidneys contribute to calcium homeostasis by adjusting the reabsorption and excretion of filtered calcium through processes that are regulated by parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). Most of the filtered calcium is reabsorbed in the proximal tubule, primarily by paracellular mechanisms that are not sensitive to calcium-regulating hormones in physiologically relevant ways. In the distal tubule, however, calcium is reabsorbed by channels and transporters, the activity or expression of which is highly regulated and increased by PTH and 1α,25(OH)2D3. Recent research suggests that other, heretofore unrecognized factors, such as the osteocyte-specific protein sclerostin, also regulate renal calcium excretion. Clues in this regard have come from the study of humans and mice with inactivating mutations of the sclerostin gene that both have increased skeletal density, which would necessitate an increase in intestinal absorption and/or renal reabsorption of calcium. Deletion of the sclerostin gene in mice significantly diminishes urinary calcium excretion and increases fractional renal calcium reabsorption. This is associated with increased circulating 1α,25(OH)2D3 levels, whereas sclerostin directly suppresses 1α-hydroxylase in immortalized proximal tubular cells. Thus, evidence is accumulating that sclerostin directly or indirectly reduces renal calcium reabsorption, suggesting the presence of a novel calcium-excreting bone-kidney axis. PMID:24876121

  7. Acute compensatory adaptation of renal function following contralateral kidney exclusion in Brattleboro rats with diabetes insipidus.

    PubMed Central

    Shirley, D G; Skinner, J

    1978-01-01

    1. The function of the remaining kidney following ligation of a single renal pedicle in anaesthetized rats with hereditary hypothalamic diabetes insipidus (DI) was studied using clearance methods. Values were compared with those obtained in DI rats which had been sham operated. 2. A small increase in the glomerular filtration rate of the remaining kidney was observed, which was statistically significant after 150 min. Increases in effective renal plasma flow were also observed, but these were not statistically significant. 3. The fractional excretion rates of Na and K increased immediately after contralateral kidney ligation; as a result total Na and K excretion rates remained similar to values in sham operated animals with both kidneys intact. 4. Fractional urine flow (V/GFR) increased by approximately 40% after contralateral ligation. It is argued that, since water reabsorption in the diluting segments of the nephron was unlikely to have been reduced, the increase in V/GFR was an indication that fractional fluid reabsorption in the proximal nephron had been inhibited. 5. Clearance determinations showed that the fractional reabsorption of Na in the proximal nephron was similarly reduced after contralateral ligation. However, Na reabsorption in the distal nephron increased, though not by enough to prevent a doubling of fractional sodium excretion. 6. The osmolalities of interstitial fluids obtained from the medulla and papilla of the contralateral kidney 2 hr after unilateral renal pedicle ligation were slightly, but significantly, higher than corresponding values in sham operated rats. This raises the possibility that salt reabsorption in the ascending limb of Henle might be enhanced immediately after contralateral renal exclusion. PMID:722584

  8. Renal abnormalities in sickle cell disease.

    PubMed

    Ataga, K I; Orringer, E P

    2000-04-01

    Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the

  9. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

    PubMed

    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.

  10. Evidence for altered renal tubule function in idiopathic calcium stone formers

    PubMed Central

    Worcester, Elaine M.; Coe, Fredric L.

    2013-01-01

    Patients who form calcium kidney stones often have metabolic disorders such as idiopathic hypercalciuria (IH) that reflect abnormalities in mineral handling in the kidney. Renal handling of calcium is altered by ingestion of nutrients such as carbohydrates, protein, and sodium, and patients with IH appear to be more sensitive to these stimuli. Studies using probes such as diuretics or lithium clearance have the ability to clarify which nephron segments are involved in the altered renal calcium transport with nutrient seen in IH. Studies in the genetic hypercalciuric rat demonstrate alterations in both proximal tubule and thick ascending limb calcium reabsorption. Similar studies in humans have begun to provide evidence about the corresponding abnormalities in stone formers with IH. A pattern of altered renal tubule transport in calcium stone formers is suggested by the frequency of such findings as decreased tubular maximal reabsorption of phosphate and abnormal urine acidification as well as hypercalciuria in such patients, not explained by monogenic transport abnormalities. PMID:20632168

  11. Inhibition of renal Na{sup +}/H{sup +} exchange in cadmium-intoxicated rats

    SciTech Connect

    Ahn, Do Whan; Chung, Jin Mo; Kim, Jee Yeun; Kim, Kyoung Ryong; Park, Yang Saeng . E-mail: yspark@ns.kosinmed.or.kr

    2005-04-01

    Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl{sub 2} (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in V{sub max} of Na{sup +}/H{sup +} antiport with no changes in K{sub Na} in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na{sup +}/H{sup +} exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na{sup +}-HCO{sub 3}{sup -} cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na{sup +}-K{sup +}-ATPase {alpha}-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading to bicarbonaturia in an intact animal.

  12. Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct.

    PubMed

    Cheng, Chih-Jen; Baum, Michel; Huang, Chou-Long

    2013-02-15

    Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is a kinase-deficient variant of WNK1 that is expressed exclusively in the kidney. It is abundantly expressed in the distal convoluted tubule (DCT) and to a lesser extent in the cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct (CCD). KS-WNK1 inhibits Na(+)-K(+)-2Cl(-)- and sodium chloride cotransporter-mediated Na(+) reabsorption in cTAL and DCT, respectively. Here, we investigated the role of KS-WNK1 in regulating Na(+) and K(+) transport in CCD using in vitro microperfusion of tubules isolated from KS-WNK1 knockout mice and control wild-type littermates. Because baseline K(+) secretion and Na(+) reabsorption were negligible in mouse CCD, we studied tubules isolated from mice fed a high-K(+) diet for 2 wk. Compared with that in wild-type tubules, K(+) secretion was reduced in KS-WNK1 knockout CCD perfused at a low luminal fluid rate of ~1.5 nl/min. Na(+) reabsorption and the lumen-negative transepithelial potential difference were also lower in the KS-WNK1 knockout CCD compared with control CCD. Increasing the perfusion rate to ~5.5 nl/min stimulated K(+) secretion in the wild-type as well as knockout CCD. The magnitudes of flow-stimulated increase in K(+) secretion were similar in wild-type and knockout CCD. Maxi-K(+) channel inhibitor iberiotoxin had no effect on K(+) secretion when tubules were perfused at ~1.5 nl/min, but completely abrogated the flow-dependent increase in K(+) secretion at ~5.5 nl/min. These findings support the notion that KS-WNK1 stimulates ROMK-mediated K(+) secretion, but not flow-dependent K(+) secretion mediated by maxi-K(+) channels in CCD. In addition, KS-WNK1 plays a role in regulating Na(+) transport in the CCD.

  13. Fluid filtration and reabsorption across microvascular walls: control by oncotic or osmotic pressure? (secondary publication).

    PubMed

    Bulat, Marin; Klarica, Marijan

    2014-08-28

    Relationships between hydrostatic and oncotic (colloid osmotic) pressures in both capillaries and interstitium are used to explain fluid filtration and reabsorption across microvascular walls. These pressures are incorporated in the Starling oncotic hypothesis of capillaries which fails, however, to explain fluid homeostasis when hydrostatic capillary pressure is high (in feet during orthostasis) and low (in lungs), or when oncotic plasma pressure is significantly decreased in experiments and some clinical states such as genetic analbuminaemia. To explain fluid homeostasis we propose osmotic counterpressure hypothesis of capillaries which claims: 1) during water filtration across microvascular wall in arterial capillary, the plasma osmolytes are sieved (retained) so that plasma osmotic counterpressure is generated, 2) this osmotic counterpressure rises along the length of capillary and when it reaches capillary hydrostatic pressure the water filtration is halted, and 3) in venous capillaries and postcapillary venules where hydrostatic pressure is low, the osmotic counterpressure is instrumental in water reabsorption from interstitium what leads to dissipation of osmotic counterpressure. According to modified van’t Hoff’s equation the generation of osmotic counterpressure depends on plasma concentration of osmolytes and their restricted passage (reflection coefficient) across microvascular wall in comparison to water. Plasma NaCl makes 83% of plasma osmolarity and shows restricted passage across the walls of cerebral and peripheral continuous capillaries, so that Na and Cl are the most important osmolytes for generation of osmotic counterpressure. Our calculation indicates that at various rates of water filtration the osmotic counterpressure of NaCl acts as negative feedback control: higher hydrostatic pressure and water filtration rate create higher osmotic counterpressure which opposes filtration and leads to higher water reabsorption rate. Furthermore, our

  14. Renal neurohormonal regulation in heart failure decompensation.

    PubMed

    Jönsson, Sofia; Agic, Mediha Becirovic; Narfström, Fredrik; Melville, Jacqueline M; Hultström, Michael

    2014-09-01

    Decompensation in heart failure occurs when the heart fails to balance venous return with cardiac output, leading to fluid congestion and contributing to mortality. Decompensated heart failure can cause acute kidney injury (AKI), which further increases mortality. Heart failure activates signaling systems that are deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin-angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal blood flow (RBF) and increase tubular sodium reabsorption, which may increase renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin contributes to venous congestion through aquaporin-mediated water retention. Additional water retention may be mediated through vasopressin-induced medullary urea transport and hyaluronan but needs further study. In addition, there are several systems that could protect the kidneys and reduce fluid retention such as natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of natriuretic peptides and nitric oxide are blunted in decompensation, partly due to oxidative stress. This review considers how neurohormonal signaling in heart failure drives fluid retention by the kidneys and thus exacerbates decompensation. It further identifies areas where there is limited data, such as signaling systems 20-HETE, purines, endothelin, the role of renal water retention mechanisms for congestion, and renal hypoxia in AKI during heart failure.

  15. Fluid reabsorption and ion transport by the lower Malpighian tubules of adult female Drosophila.

    PubMed

    O'Donnell, M J; Maddrell, S H

    1995-08-01

    The properties of the Malpighian tubules of Drosophila melanogaster change along their length. The upstream main segments secrete K(+)-rich fluid at a high rate. From this, the lower tubules reabsorb significant amounts of water and K+. Under stimulation, K+ reabsorption is accelerated. In addition, the lower tubules acidify the fluid passed to them by the main segments and secrete Ca2+ into it, adding to that transported there by the upstream epithelium. In contrast to the lumen-positive transepithelial potential difference (TEP) of the main segments, the TEP in the lower tubules is much lower and becomes lumen-negative close to their downstream junction with the common ureter. We suggest that the role of the lower tubule is to reduce the flow of K(+)-rich fluid that passes to the hindgut; this allows the hindgut to process the flow of excretory fluid more thoroughly.

  16. Tuning luminescence and reducing reabsorption of CdSe quantum disks forluminescent solar concentrators.

    PubMed

    Lin, Huichuan; Xie, Peng; Liu, Yong; Zhou, Xiang; Li, Baojun

    2015-08-21

    Cadmium selenide (CdSe) quantum disks (QDs) have been synthesized for application in luminescent solar concentrators (LSCs). Luminescence tuning and reabsorption reduction of the QDs were achieved by controlling their size using a hot injection method. The overlap of the absorption and photoluminescence spectra of the as-prepared CdSe QDs was negligible. The as-prepared CdSe QDs were incorporated into polymethylmethacrylate without aggregation and luminescence quenching. The obtained highly transparent composites with non-affecting light-emitting properties were used as LSCs. The placement of a CdSe QDs doped LSC prototype (10 × 1 × 0.1 cm) on a Si-cell resulted in a 201% increase in the electrical power output of the Si-cell compared with that of the bare Si-cell.

  17. Tuning luminescence and reducing reabsorption of CdSe quantum disks for luminescent solar concentrators

    NASA Astrophysics Data System (ADS)

    Lin, Huichuan; Xie, Peng; Liu, Yong; Zhou, Xiang; Li, Baojun

    2015-08-01

    Cadmium selenide (CdSe) quantum disks (QDs) have been synthesized for application in luminescent solar concentrators (LSCs). Luminescence tuning and reabsorption reduction of the QDs were achieved by controlling their size using a hot injection method. The overlap of the absorption and photoluminescence spectra of the as-prepared CdSe QDs was negligible. The as-prepared CdSe QDs were incorporated into polymethylmethacrylate without aggregation and luminescence quenching. The obtained highly transparent composites with non-affecting light-emitting properties were used as LSCs. The placement of a CdSe QDs doped LSC prototype (10 × 1 × 0.1 cm) on a Si-cell resulted in a 201% increase in the electrical power output of the Si-cell compared with that of the bare Si-cell.

  18. Core/shell quantum dot based luminescent solar concentrators with reduced reabsorption and enhanced efficiency.

    PubMed

    Coropceanu, Igor; Bawendi, Moungi G

    2014-07-09

    CdSe/CdS core/shell quantum dots (QDs) have been optimized toward luminescent solar concentration (LSC) applications. Systematically increasing the shell thickness continuously reduced reabsorption up to a factor of 45 for the thickest QDs studied (with ca. 14 monolayers of CdS) compared to the initial CdSe cores. Moreover, an improved synthetic method was developed that retains a high-fluorescence quantum yield, even for particles with the thickest shell volume, for which a quantum yield of 86% was measured in solution. These high quantum yield thick shell quantum dots were embedded in a polymer matrix, yielding highly transparent composites to serve as prototype LSCs, which exhibited an optical efficiency as high as 48%. A Monte Carlo simulation was developed to model LSC performance and to identify the major loss channels for LSCs incorporating the materials developed. The results of the simulation are in excellent agreement with the experimental data.

  19. Ion transporters for fluid reabsorption in the rooster (Gallus domesticus) epididymal region.

    PubMed

    Bahr, J M; Dalponte, M; Janssen, S; Bunick, D; Nakai, M

    2006-10-01

    Testicular fluid is highly condensed during its passage through the epididymal region in the avian species. In the present study, major ion transporters that are responsible for condensation mainly by water resorption in the reproductive tract as identified in the mammalian epididymis were localized within the rooster (Gallus domesticus) epididymis by immunohistochemistry. The results show that the efferent ductule epithelium expressed sodium-potassium ATPase (Na(+),K(+)-ATPase), carbonic anhydrase II (CAII) and sodium hydrogen exchanger isoform 3 (NHE3) and that the connecting ductule and epididymal duct epithelia expressed Na(+),K(+)-ATPase and CAII. These data suggest that a model proposed for reabsorption in mammalian efferent ductules can be applied to avian efferent ductules.

  20. Urinary and renal papillary solutes during cyclooxygenase inhibition with ibuprofen

    SciTech Connect

    Passmore, J.C.; Hartupee, D.A.; Jackson, B.A.

    1987-12-01

    We investigated the mechanisms by which prostaglandin synthetase (cyclooxygenase) inhibitors cause antidiuresis and antinatriuresis in anesthetized dogs. Cyclooxygenase inhibition with ibuprofen caused an increased total solute (Na+, K+, and urea) concentration in the renal papilla. Xenon 133 washout studies revealed no change in medullary blood flow. Ibuprofen induced a 147% increase in papillary Na+ concentration, while increasing urea and K+ only 98% and 35%, respectively, suggesting that a Na+ reabsorption mechanism rather than decreased papillary blood flow was responsible for a majority of the increased papillary solute concentration. A decrease in the excretion of Na+, but not of K+ or urea, in treated dogs further implies increased Na+ reabsorption. Thus, it appears that cyclooxygenase inhibition increases papillary solute concentration primarily by increasing Na+ transport into the papilla.

  1. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero g or space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast 5 of the 7 remaining rats increased the fraction of the filtered sodium excreted (C sub Na/GFR, p .05) and their urinary flow rate (V, p .05). Potassium excretion increased (U sub k V, p .05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause, in rats, a decrease in distal tubular sodium, water and potassium reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis.

  2. Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

    PubMed

    Mudaliar, Sunder; Polidori, David; Zambrowicz, Brian; Henry, Robert R

    2015-12-01

    Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors.

  3. Cellular mechanisms of renal adaptation of sodium dependent sulfate cotransport to altered dietary sulfate in rats.

    PubMed

    Sagawa, K; DuBois, D C; Almon, R R; Murer, H; Morris, M E

    1998-12-01

    The renal transport and fractional reabsorption of inorganic sulfate is altered under conditions of sulfate deficiency or excess. The objective of this study was to examine the cellular mechanisms of adaptation of renal sodium/sulfate cotransport after varying dietary intakes of a sulfur containing amino acid, methionine. Female Lewis rats were divided into four groups and fed diets containing various concentrations of methionine (0, 0.3, 0.82 and 2.46%) for 8 days. Urinary excretion rates and renal clearance of sulfate were significantly decreased in the animals fed a 0% methionine diet or a 0.3% methionine diet, and significantly increased in the animals fed a 2.46% methionine diet when evaluated on days 4 and 7. Serum sulfate concentrations were unchanged by diet treatment in all animals. The fractional reabsorption of sulfate was significantly increased in the animals fed the 0% methionine diet and the 0.3% methionine diets, and decreased in the animals fed the 2.46% methionine diet. Increased mRNA and protein levels for the sodium/sulfate transporter (NaSi-1) were found in the kidney cortex following treatment with the 0 and 0.3% methionine diet groups. Sulfate homeostasis by renal reabsorption is maintained by an up-regulation of steady state levels of NaSi-1 mRNA and protein when the diet is low in methionine.

  4. Challenges and intriguing problems in comparative renal physiology.

    PubMed

    Dantzler, William H

    2005-02-01

    The comparative approach has proved important many times in understanding renal function and continues to offer possible approaches to unsolved problems today, in three general areas. (1) Quantification of glomerular ultrafiltration. In contrast to the complex capillary network in the mammalian glomerulus, the glomerulus of the superficial loopless (reptilian-type) avian nephrons consists of a single capillary loop. This structure, in an avian species where it can be approached directly, should for the first time permit accurate determinations of the pressure profiles and the capillary area involved in glomerular ultrafiltration in an animal with high arterial pressure. (2) Fluid reabsorption by proximal renal tubules. In some reptilian proximal renal tubules, isolated and perfused in vitro, isosmotic fluid reabsorption can occur at control rates when lithium replaces sodium or when some other substance replaces sodium or chloride or both in the perfusate and bathing medium simultaneously. Reabsorption at the control rates, regardless of the composition of the perfusate and bathing medium, can be at least partially inhibited by cold and cyanide, but not by blockers of Na(+)-K(+)-ATPase. It is also independent of the buffer system used, but it is reduced about 20% by removal of colloid from the peritubular fluid. During the substitutions, the surface area of the proximal tubule cells increases dramatically and might permit some insignificant force to be more effective in the reabsorptive process. Understanding the process involved in this, apparently unique coupling of solute and fluid transport, certainly would be very valuable in understanding coupled transport of solutes and water across epithelia in general. (3) Urate secretion by proximal renal tubules. Urate is the major excretory end product of nitrogen metabolism in birds, most reptiles, and a few amphibians. It undergoes net secretion by the renal tubules. It has been possible to learn much about the

  5. Renal clearance of endogenous creatinine, urea, sodium, and potassium in normal cats and cats with chronic renal failure.

    PubMed

    Deguchi, E; Akuzawa, M

    1997-07-01

    The renal clearance test was carried out in 6 normal male cats and 12 male cats with chronic renal failure. The average concentrations of creatinine (Cr), urea, sodium (Na), and potassium (K) in the serum of the cats with chronic renal failure were 5.09, 136.7 (mg/100 ml), 143.9 and 3.71 (mEq/l) respectively, and the specific gravity of urine was 1.009. The renal clearances of Cr, urea, Na, and K (ml/min/kg of body weight) were 2.639 +/- 0.217, 1.034 +/- 0.110, 0.024 +/- 0.007 and 0.266 +/- 0.028, respectively in normal cats, and were 0.789 +/- 0.407, 0.358 +/- 0.211, 0.095 +/- 0.084 and 0.872 +/- 0.204 in cats with chronic renal failure. Clearance of Cr and urea was significantly lower in cats with chronic renal failure than in normal cats, while the values of Na and K were significantly higher in cats with chronic renal failure. The glomerular filtration of Cr and urea and the urinary excretion of these 4 substances were significantly higher in cats with chronic renal failure. The tubular reabsorption rates of Na and K were significantly lower in cats with chronic renal failure compared to those in normal cats, but there was no significant difference in urea and creatinine.

  6. Cryoglobulinemia and renal disease.

    PubMed

    Alpers, Charles E; Smith, Kelly D

    2008-05-01

    Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy. The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease. The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.

  7. Renal function in cyanotic congenital heart disease.

    PubMed

    Burlet, A; Drukker, A; Guignard, J P

    1999-01-01

    We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.

  8. PTH modulation of NCC activity regulates TRPV5 Ca2+ reabsorption.

    PubMed

    Hoover, Robert S; Tomilin, Viktor; Hanson, Lauren; Pochynyuk, Oleh; Ko, Benjamin

    2016-01-15

    Since parathyroid hormone (PTH) is known to increase transient receptor potential vanilloid (TRPV)5 activity and decrease Na(+)-Cl(-) cotransporter (NCC) activity, we hypothesized that decreased NCC-mediated Na(+) reabsorption contributes to the enhanced TRPV5 Ca(2+) reabsorption seen with PTH. To test this, we used mDCT15 cells expressing functional TRPV5 and ruthenium red-sensitive (45)Ca(2+) uptake. PTH increased (45)Ca(2+) uptake to 8.8 ± 0.7 nmol·mg(-1)·min(-1) (n = 4, P < 0.01) and decreased NCC activity from 75.4 ± 2.7 to 20.3 ± 1.3 nmol·mg(-1)·min(-1) (n = 4, P < 0.01). Knockdown of Ras guanyl-releasing protein (RasGRP)1 had no baseline effect on (45)Ca(2+) uptake but significantly attenuated the response to PTH from a 45% increase (6.0 ± 0.2 to 8.7 ± 0.4 nmol·mg(-1)·min(-1)) in control cells to only 20% in knockdown cells (6.1 ± 0.1 to 7.3 ± 0.2 nmol·mg(-1)·min(-1), n = 4, P < 0.01). Inhibition of PKC and PKA resulted in further attenuation of the PTH effect. RasGRP1 knockdown decreased the magnitude of the TRPV5 response to PTH (7.9 ± 0.1 nmol·mg(-1)·min(-1) for knockdown compared with 9.1 ± 0.1 nmol·mg(-1)·min(-1) in control), and the addition of thiazide eliminated this effect (a nearly identical 9.0 ± 0.1 nmol·mg(-1)·min(-1)). This indicates that functionally active NCC is required for RasGRP1 knockdown to impact the PTH effect on TRPV5 activity. Knockdown of with no lysine kinase (WNK)4 resulted in an attenuation of the increase in PTH-mediated TRPV5 activity. TRPV5 activity increased by 36% compared with 45% in control (n = 4, P < 0.01 between PTH-treated groups). PKC blockade further attenuated the PTH effect, whereas combined PKC and PKA blockade in WNK4KD cells abolished the effect. We conclude that modulation of NCC activity contributes to the response to PTH, implying a role for hormonal modulation of NCC activity in distal Ca(2+) handling.

  9. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males.

    PubMed

    Shen, Zancong; Rowlings, Colin; Kerr, Brad; Hingorani, Vijay; Manhard, Kimberly; Quart, Barry; Yeh, Li-Tain; Storgard, Chris

    2015-01-01

    Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration-time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated.

  10. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males

    PubMed Central

    Shen, Zancong; Rowlings, Colin; Kerr, Brad; Hingorani, Vijay; Manhard, Kimberly; Quart, Barry; Yeh, Li-Tain; Storgard, Chris

    2015-01-01

    Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration–time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated. PMID:26170627

  11. The iron reabsorption index: a new phenotypic and pathophysiological descriptor in HFE hemochromatosis.

    PubMed

    Manet, Ghislain; Bardou-Jacquet, Edouard; Perrin, Michèle; Morcet, Jeff; Sinteff, Jean-Paul; Lainé, Fabrice; Moirand, Romain; Deugnier, Yves

    2013-11-01

    The current phenotypic descriptors of high Fe gene hemochromatosis are hardly specific and time dependent in a context of highly variable expressivity. We hypothesized that the rate of iron removed during maintenance therapy and corresponding to the iron reabsorption index (IRI) could be patient specific and may then represent a new useful phenotypic marker. The present study aimed to describe IRI with respect to its phenotypic specificity and to its potential usefulness. We studied a cohort of 316 p.Cys282Tyr homozygous patients with stable low serum ferritin levels on maintenance therapy for at least 12 months. Characteristics at diagnosis, date and volume of phlebotomies, and parameters of iron metabolism throughout maintenance therapy were determined. IRI ranged from 1.3 to 6.1 mg/day (median: 2.44). It was lower in women (difference: 1.26 mg/day), mainly explained by physiological blood loss, weight, and alcohol consumption. IRI was correlated to iron burden and fibrosis stage at diagnosis, was stable over time (variation: 11.5%), and depended on serum ferritin level during therapy. Its independence from disease duration, its stability, its wide distribution, and its significant correlation with iron burden markers make IRI a valuable potential phenotypic indicator of the daily iron overabsorption in hemochromatosis. Moreover, IRI provides a conceptual frame for empiric adaptation of maintenance therapy.

  12. Icodextrin re-absorption varies with age in children on automated peritoneal dialysis.

    PubMed

    Dart, Allison; Feber, Janusz; Wong, Hubert; Filler, Guido

    2005-05-01

    Information on the use of Icodextrin in children remains scarce; however, it is believed that the characteristics are similar across all ages. We report the use of Icodextrin in a cohort of pediatric automated peritoneal dialysis (APD) patients younger than those previously reported (n=8, median age of 2.8, range 0.02-17.1 years). Net Icodextrin daytime dwell ultrafiltration was calculated in each patient for every day on therapy as ml/h/m2. Half of the patients showed re-absorption even when reducing Icodextrin dwells from a median of 10 to 6 h. All four patients who re-absorbed the Icodextrin (ranging from -23.7+/-7.5 to -2.5+/-6.0 ml/h/m2) were treated with cyclic nocturnal APD, and three of these four patients were high transporters on the peritoneal equilibration test (PET). Icodextrin fluid removal correlated significantly with age (Spearman rank r=0.8571, P=0.0107). The data suggest that Icodextrin behaves differently in young children.

  13. Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption.

    PubMed

    Kang, Kihwa; Schmahl, Jennifer; Lee, Jong-Min; Garcia, Karen; Patil, Ketan; Chen, Amelia; Keene, Michelle; Murphy, Andrew; Sleeman, Mark W

    2012-01-01

    Ghrelin is a unique peptide gut hormone that requires post-translational modification to stimulate both feeding and growth hormone release. Ghrelin O-acyltransferase (GOAT) was identified as a specific acyl-transferase for ghrelin, and recent genetic deletion studies of the Goat gene (Goat(-/-)) uncovered the role of ghrelin in the regulation of glucose homeostasis. To further understand the physiological functions of the GOAT/ghrelin system, we have conducted a metabolomic and microarray profile of Goat-null mice, as well as determined Goat expression in different tissues using the lacZ reporter gene. Serum metabolite profile analysis revealed that Goat(-/-) mice exhibited increased secondary bile acids >2.5-fold. This was attributed to increased mRNA and protein expression of the ileal sodium-dependent bile acid transporter (ISBT) in the intestinal and biliary tract. Increased expression of additional solute carrier proteins, including Slc5a12 (>10-fold) were also detected in the small intestine and bile duct. Goat staining was consistently observed in the pituitary glands, stomach, and intestines, and to a lesser extent in the gallbladder and pancreatic duct. This is the first report that the GOAT/ghrelin system regulates bile acid metabolism, and these findings suggest a novel function of GOAT in the regulation of intestinal bile acid reabsorption..

  14. Renal distal tubular handling of sodium in central fluid volume homoeostasis in preascitic cirrhosis

    PubMed Central

    Sansoe, G; Ferrari, A; Baraldi, E; Castellana, C; De Santis, M C; Manenti, F

    1999-01-01

    BACKGROUND/AIMS—Patients with preascitic liver cirrhosis have an increased central plasma volume, and, for any given plasma aldosterone concentration, they excrete less sodium than healthy controls. A detailed study of the distribution of sodium reabsorption along the segments of the renal tubule, especially the distal one, is still lacking in preascitic cirrhosis.
METHODS—Twelve patients with Child-Pugh class A cirrhosis and nine control subjects (both groups on a normosodic diet) were submitted to the following investigations: (a) plasma levels of active renin and aldosterone; (b) four hour renal clearance of lithium (an index of fluid delivery to the loop of Henle), creatinine, sodium, and potassium; (c) dopaminergic activity, as measured by incremental aldosterone response to intravenous metoclopramide.
RESULTS—Metoclopramide induced higher incremental aldosterone responses, indicating increased dopaminergic activity in patients than controls, which is evidence of an increased central plasma volume (+30 min: 160.2 (68.8) v 83.6 (35.2) pg/ml, p<0.01; +60 min: 140.5 (80.3) v 36.8 (36.1) pg/ml, p<0.01). Patients had increased distal fractional sodium reabsorption compared with controls (26.9 (6.7)% v 12.5 (3.4)% of the filtered sodium load, p<0.05). In the patient group there was an inverse correlation between: (a) absolute distal sodium reabsorption and active renin (r −0.59, p<0.05); (b) fractional distal sodium reabsorption and sodium excretion (r −0.66, p<0.03).
CONCLUSIONS—These data suggest that in preascitic cirrhosis the distal fractional tubular reabsorption of sodium is increased and critical in regulating both central fluid volume and sodium excretion.


Keywords: kidney; sodium handling; lithium clearance; liver cirrhosis; dopamine; central fluid volume PMID:10517915

  15. Validation of phenol red versus gravimetric method for water reabsorption correction and study of gender differences in Doluisio's absorption technique.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Gonzalez-Alvarez, Isabel; Gonzalez-Alvarez, Marta; Bermejo, Marival

    2014-10-01

    The aim of the present study was to develop a method for water flux reabsorption measurement in Doluisio's Perfusion Technique based on the use of phenol red as a non-absorbable marker and to validate it by comparison with gravimetric procedure. The compounds selected for the study were metoprolol, atenolol, cimetidine and cefadroxil in order to include low, intermediate and high permeability drugs absorbed by passive diffusion and by carrier mediated mechanism. The intestinal permeabilities (Peff) of the drugs were obtained in male and female Wistar rats and calculated using both methods of water flux correction. The absorption rate coefficients of all the assayed compounds did not show statistically significant differences between male and female rats consequently all the individual values were combined to compare between reabsorption methods. The absorption rate coefficients and permeability values did not show statistically significant differences between the two strategies of concentration correction. The apparent zero order water absorption coefficients were also similar in both correction procedures. In conclusion gravimetric and phenol red method for water reabsorption correction are accurate and interchangeable for permeability estimation in closed loop perfusion method. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich-Wistar rat.

    PubMed Central

    Maddox, D A; Horn, J F; Famiano, F C; Gennari, F J

    1986-01-01

    Studies were undertaken to characterize the pattern of proximal tubular fluid (APRH2O) and bicarbonate reabsorption (APRHCO3) in the remnant kidney of euvolemic Munich-Wistar rats. The remnant kidney rats were placed on a diet containing either low or normal protein. Collections were obtained in the early, mid-, and late proximal convoluted tubule. Single nephron glomerular filtration rate (SNGFR) increased from 40.2 nl/min in controls to 58.8 nl/min in low protein remnant kidney and 78.1 nl/min in normal protein remnant kidney rats. The filtered load of bicarbonate was 1,272, 1,641, and 2,013 pmol/min, in the three groups, respectively. APRH2O and APRHCO3 increased nearly in parallel. Most of the increase in reabsorption occurred in the early proximal tubule. Tubular hypertrophy could account for at least 20-40% of the increase in reabsorption, but the majority of the increase appeared to be a delivery-dependent response similar to that observed in normal rats after an acute increase in SNGFR. Images PMID:3009550

  17. Steady-State Fluorescence of Highly Absorbing Samples in Transmission Geometry: A Simplified Quantitative Approach Considering Reabsorption Events.

    PubMed

    Krimer, Nicolás I; Rodrigues, Darío; Rodríguez, Hernán B; Mirenda, Martín

    2017-01-03

    A simplified methodology to acquire steady-state emission spectra and quantum yields of highly absorbing samples is presented. The experimental setup consists of a commercial spectrofluorometer adapted to transmission geometry, allowing the detection of the emitted light at 180° with respect to the excitation beam. The procedure includes two different mathematical approaches to describe and reproduce the distortions caused by reabsorption on emission spectra and quantum yields. Toluene solutions of 9,10-diphenylanthracence, DPA, with concentrations ranging between 1.12 × 10(-5) and 1.30 × 10(-2) M, were used to validate the proposed methodology. This dye has significant probability of reabsorption and re-emission in concentrated solutions without showing self-quenching or aggregation phenomena. The results indicate that the reabsorption corrections, applied on molecular emission spectra and quantum yields of the samples, accurately reproduce experimental data. A further discussion is performed concerning why the re-emitted radiation is not detected in the experiments, even at the highest DPA concentrations.

  18. Photon Reabsorption Masks Intrinsic Bimolecular Charge-Carrier Recombination in CH3NH3PbI3 Perovskite.

    PubMed

    Crothers, Timothy W; Milot, Rebecca L; Patel, Jay B; Parrott, Elizabeth S; Schlipf, Johannes; Müller-Buschbaum, Peter; Johnston, Michael B; Herz, Laura M

    2017-08-14

    An understanding of charge-carrier recombination processes is essential for the development of hybrid metal halide perovskites for photovoltaic applications. We show that typical measurements of the radiative bimolecular recombination constant in CH3NH3PbI3 are strongly affected by photon reabsorption that masks a much larger intrinsic bimolecular recombination rate constant. By investigating a set of films whose thickness varies between 50 and 533 nm, we find that the bimolecular charge recombination rate appears to slow by an order of magnitude as the film thickness increases. However, by using a dynamical model that accounts for photon reabsorption and charge-carrier diffusion we determine that a single intrinsic bimolecular recombination coefficient of value 6.8 × 10(-10) cm(3)s(-1) is common to all samples irrespective of film thickness. Hence, we postulate that the wide range of literature values reported for such coefficients is partly to blame on differences in photon out-coupling between samples with crystal grains or mesoporous scaffolds of different sizes influencing light scattering, whereas thinner films or index-matched surrounding layers can reduce the possibility for photon reabsorption. We discuss the critical role of photon confinement on free charge-carrier retention in thin photovoltaic layers and highlight an approach to assess the success of such schemes from transient spectroscopic measurement.

  19. A Renal Olfactory Receptor Aids in Kidney Glucose Handling

    PubMed Central

    Shepard, Blythe D.; Cheval, Lydie; Peterlin, Zita; Firestein, Stuart; Koepsell, Hermann; Doucet, Alain; Pluznick, Jennifer L.

    2016-01-01

    Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels. Consistent with this phenotype, Olfr1393 knockout mice have a significant decrease in luminal expression of Sglt1, a key renal glucose transporter, uncovering a novel regulatory pathway involving Olfr1393 and Sglt1. In addition, by utilizing a large scale screen of over 1400 chemicals we reveal the ligand profile of Olfr1393 for the first time, offering new insight into potential pathways of physiological regulation for this novel signaling pathway. PMID:27739476

  20. Molecular bases of circadian rhythmicity in renal physiology and pathology

    PubMed Central

    Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

    2013-01-01

    The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

  1. The influence of salt intake on the metabolic acidosis of chronic renal failure

    PubMed Central

    Espinel, G H

    1975-01-01

    The influence of dietary salt on the levels of plasma bicarbonate and on the characteristics of bicarbonate reabsorption was studied in experimental chronic renal failure. Chronic renal failure was produced in rats by sequential partial nephrectomies. The control group received a diet constant in salt content throughout the progression of renal failure; the other group (PRNa), at each stage of renal failure, received salt intake reduced in direct proportion to the fall in glomerular filtration rate (GFR). In the steady state, the quantities of urinary sodium closely approximated intake in obth groups of animals. The adaptive increased natriuresis per nephron exhibited by the control animals was prevented in the PRNa animals. The PRNa group had (a) higher plasma bicarbonate levels, (b) increased bicarbonate thresholds, and (c) increased maximal tubular reabsorptive capacity for bicarbonate. As renal failure progresses, dietary salt can become a determining factor of the levels at which plasma bicarbonate is maintained. Proportional reduction of dietary salt results in bicarbonate conservation in rats with experimental progressive renal failure. PMID:1150871

  2. Renal sodium excretion in sons of hypertensive parents.

    PubMed

    Turner, S T; Reilly, S L

    1993-09-01

    The objective of this study was to evaluate whether renal excretion of sodium is impaired and whether tubular reabsorption of sodium is increased in normotensive white men with a familial predisposition to develop essential hypertension. We compared 11 normotensive sons of two hypertensive parents (SOHT) with 11 normotensive sons of two normotensive parents (SONT); renal sodium handling was assessed after 1 week of low-sodium diet (10 mmol/d) and after 1 week of high-sodium diet (200 mmol/d). The SOHT were on average 5.5 years older than the SONT (46.9 +/- 5.2 [SD] vs 41.4 +/- 4.1, P = .012). On the sixth day of each diet, mean urinary sodium excretion did not differ between the two groups (12.9 +/- 6.3 vs 12.7 +/- 6.7 mmol/d on low-sodium diet, P = .930; 197 +/- 25 vs 200 +/- 27 mmol/d on high-sodium diet, P = .817). On the seventh day of each diet, baseline means for filtered load of sodium, absolute excretion of sodium, fractional excretion of sodium (an index of total tubular sodium reabsorption), and fractional excretion of lithium (an inverse index of proximal tubular sodium reabsorption) also did not differ between the groups. To assess renal sodium handling under non-steady-state conditions, we infused 2 L normal saline intravenously over a 2-hour period. The means for absolute excretion of sodium, fractional excretion of sodium, and fractional excretion of lithium increased from baseline, but the increases did not differ in magnitude between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Laparoscopic Renal Cryoablation

    PubMed Central

    Schiffman, Marc; Moshfegh, Amiel; Talenfeld, Adam; Del Pizzo, Joseph J.

    2014-01-01

    In light of evidence linking radical nephrectomy and consequent suboptimal renal function to adverse cardiovascular events and increased mortality, research into nephron-sparing techniques for renal masses widely expanded in the past two decades. The American Urological Association (AUA) guidelines now explicitly list partial nephrectomy as the standard of care for the management of T1a renal tumors. Because of the increasing utilization of cross-sectional imaging, up to 70% of newly detected renal masses are stage T1a, making them more amenable to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. Cryosurgery has emerged as a leading option for renal ablation, and compared with surgical techniques it offers benefits in preserving renal function with fewer complications, shorter hospitalization times, and allows for quicker convalescence. A mature dataset exists at this time, with intermediate and long-term follow-up data available. Cryosurgical recommendations as a first-line therapy are made at this time in limited populations, including elderly patients, patients with multiple comorbidities, and those with a solitary kidney. As more data emerge on oncologic efficacy, and technical experience and the technology continue to improve, the application of this modality will likely be extended in future treatment guidelines. PMID:24596441

  4. Dietary Intake as a Link between Obesity, Systemic Inflammation, and the Assumption of Multiple Cardiovascular and Antidiabetic Drugs in Renal Transplant Recipients

    PubMed Central

    Guida, Bruna; Maresca, Immacolata Daniela; Germanò, Roberta; Trio, Rossella; Nastasi, Anna Maria; Federico, Stefano; Memoli, Andrea; Apicella, Luca; Memoli, Bruno; Sabbatini, Massimo

    2013-01-01

    We evaluated dietary intake and nutritional-inflammation status in ninety-six renal transplant recipients, 7.2 ± 5.0 years after transplantation. Patients were classified as normoweight (NW), overweight (OW), and obese (OB), if their body mass index was between 18.5 and 24.9, 25.0 and 29.9, and ≥30 kg/m2, respectively. Food composition tables were used to estimate nutrient intakes. The values obtained were compared with those recommended in current nutritional guidelines. 52% of the patients were NW, 29% were OW, and 19% were OB. Total energy, fat, and dietary n-6 PUFAs intake was higher in OB than in NW. IL-6 and hs-CRP were higher in OB than in NW. The prevalence of multidrug regimen was higher in OB. In all patients, total energy, protein, saturated fatty acids, and sodium intake were higher than guideline recommendations. On the contrary, the intake of unsaturated and n-6 and n-3 polyunsaturated fatty acids and fiber was lower than recommended. In conclusion, the prevalence of obesity was high in our patients, and it was associated with inflammation and the assumption of multiple cardiovascular and antidiabetic drugs. Dietary intake did not meet nutritional recommendations in all patients, especially in obese ones, highlighting the need of a long-term nutritional support in renal transplant recipients. PMID:23984354

  5. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  6. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  7. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  8. Obesity and renal cancer

    PubMed Central

    Gati, Asma; Kouidhi, Soumaya; Marrakchi, Raja; El Gaaied, Amel; Kourda, Nadia; Derouiche, Amine; Chebil, Mohamed; Caignard, Anne; Perier, Aurélie

    2014-01-01

    Epidemiological studies link obesity, as measured by increased body mass index (BMI) to the incidence of renal cell carcinoma (RCC) as well as to the cancer-related mortality of RCC patients. RCC is the third cancer most robustly associated with increased BMI. Understanding the role of the adipose tissue in renal carcinogenesis is therefore of major importance for the development of novel paradigms of RCC prevention and treatment. Here, we discuss the current knowledge on the impact of obesity on the development and progression of RCC as well as the role of adipose tissue-derived hormones (adipokines) in the conflict between growing tumors and the immune system. PMID:24804162

  9. The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review).

    PubMed

    Yamaguchi, Masayoshi

    2015-11-01

    The kidneys play a physiologic role in the regulation of urine formation and nutrient reabsorption in the proximal tubule epithelial cells. Kidney development has been shown to be regulated through calcium (Ca2+) signaling processes that are present through numerous steps of tubulogenesis and nephron induction during embryonic development of the kidneys. Ca2+-binding proteins, such as calbindin-D28k and regucalcin are important proteins that are commonly used as biomarkers in pronephric tubules, and the ureteric bud and metanephric mesenchyme. Previous research on regucalcin focused on Ca2+ sensors that are involved in renal organogenesis and the link between Ca2+-dependent signals and polycystins. Moreover, regucalcin has been highlighted to play a multifunctional role in kidney cell regulation. The regucalcin gene, which is localized on the X chromosome, is regulated through various transcription factors. Regucalcin has been found to regulate intracellular Ca2+ homeostasis in kidney proximal tubule epithelial cells. Regucalcin has been demonstrated to regulate the activity of various enzymes that are involved in intracellular signaling pathways. It has been noted that regucalcin suppresses DNA synthesis and regulates the gene expression of various proteins related to mineral transport, transcription factors, cell proliferation and apoptosis. The overexpression of regucalcin has been shown to exert suppressive effects on cell proliferation and apoptotic cell death, which are stimulated by various stimulatory factors. Moreover, regucalcin gene expression was found to to be involved in various pathophysiological states, including renal failure. This review discusses recent findings concerning the potential role of regucalcin as a regulatory protein in the kidney proximal tubule epithelial cells.

  10. Renal plasticity in response to feeding in the Burmese python, Python molurus bivittatus.

    PubMed

    Esbaugh, A J; Secor, S M; Grosell, M

    2015-10-01

    Burmese pythons are sit-and-wait predators that are well adapted to go long periods without food, yet subsequently consume and digest single meals that can exceed their body weight. These large feeding events result in a dramatic alkaline tide that is compensated by a hypoventilatory response that normalizes plasma pH; however, little is known regarding how plasma HCO3(-) is lowered in the days post-feeding. The current study demonstrated that Burmese pythons contain the cellular machinery for renal acid-base compensation and actively remodel the kidney to limit HCO3(-) reabsorption in the post-feeding period. After being fed a 25% body weight meal plasma total CO2 was elevated by 1.5-fold after 1 day, but returned to control concentrations by 4 days post-feeding (d pf). Gene expression analysis was used to verify the presence of carbonic anhydrase (CA) II, IV and XIII, Na(+) H(+) exchanger 3 (NHE3), the Na(+) HCO3(-) co-transporter (NBC) and V-type ATPase. CA IV expression was significantly down-regulated at 3 dpf versus fasted controls. This was supported by activity analysis that showed a significant decrease in the amount of GPI-linked CA activity in isolated kidney membranes at 3 dpf versus fasted controls. In addition, V-type ATPase activity was significantly up-regulated at 3 dpf; no change in gene expression was observed. Both CA II and NHE3 expression was up-regulated at 3 dpf, which may be related to post-prandial ion balance. These results suggest that Burmese pythons actively remodel their kidney after feeding, which would in part benefit renal HCO3(-) clearance.

  11. Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats.

    PubMed Central

    Adler, S; Zett, B; Anderson, B; Fraley, D S

    1975-01-01

    When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KC1-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of 14CO2 from (1, 5-14C) citrate. In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production. It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic responses ordinarily occur in response to acidosis, the data are consistent with the hypothesis that volume expansion reduces renal cell pH in 3KCl-deficient rats. PMID:239022

  12. Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus.

    PubMed

    Jakobsson, B; Berg, U

    1994-05-01

    The purpose of this study was to investigate the effects of treatment with hydrochlorothiazide and hydrochlorothiazide and indomethacin combined on renal function in four boys, two with nephrogenic diabetes insipidus and two with partial nephrogenic diabetes insipidus using the clearances of inulin and para-aminohippuric acid under water diuresis and lithium clearance. Hydrochlorothiazide reduced urine flow and lithium clearance. These effects were further potentiated by addition of indomethacin. No consistent effects on renal plasma flow or glomerular filtration rate were found. It is concluded that treatment with hydrochlorothiazide alone and hydrochlorothiazide and indomethacin combined reduces urine flow in nephrogenic diabetes insipidus by increasing proximal tubular reabsorption of sodium.

  13. Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome.

    PubMed

    Willnow, Thomas E; Christ, Annabel

    2017-08-01

    Megalin (or LRP2) is an endocytic receptor that plays a central role in embryonic development and adult tissue homeostasis. Loss of this receptor in congenital or acquired diseases results in multiple organ dysfunctions, including forebrain malformation (holoprosencephaly) and renal reabsorption defects (renal Fanconi syndrome). Here, we describe current concepts of the mode of receptor action that include co-receptors and a repertoire of different ligands, and we discuss how these interactions govern functional integrity of the kidney and the brain, and cause disease when defective.

  14. Angiotensin II natriuresis and anti-natriuresis: role of renal artery pressure in anaesthetized dogs.

    PubMed

    Olsen, M E; Hall, J E; Montaini, J P; Guyton, A C

    1984-12-01

    The aim of this study was to determine the role of changes in renal artery pressure (RAP), renal haemodynamics, and tubular reabsorption in mediating the natriuretic and anti-natriuretic actions of angiotensin II (ANG II). In anaesthetized dogs, endogenous ANG II formation was blocked with SQ-14225 and ANG II was infused intravenously at rates of 5-1215 ng/kg/min while RAP was either servo-controlled at the normal level or permitted to increase. When RAP was servo-controlled to prevent a rise in RAP, ANG II infusion at all rates from 5-1215 ng/kg/min decreased urinary sodium excretion (INaV) and fractional sodium excretion (FENa), while increasing fractional reabsorption of lithium (FRLi), an index of proximal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng/kg/min decreased UNaV, and FENam while increasing FRLi and FRDNa greater than However, at 135 ng/kg/min and above UNaV and FENE increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion, compared to the dogs in which RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause anti-natriuresis when RAP is prevented from increasing. The natriuretic effect of high doses of ANG II is caused by increased RAP which decreases fractional sodium reabsorption in proximal and distal tubules and causes slight increase in sodium delivery to the tubules.

  15. Renal Stones

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. The micrograph shows calcium oxalate crystals in urine. These small crystals can develop to form renal stones. Principal Investigator: Dr. Peggy Whitson, NASA Johnson Space Center, Houston, TX.

  16. Signaling Mechanisms that Link Salt Retention to Hypertension: Endogenous Ouabain, the Na+ Pump, the Na+/Ca2+ Exchanger and TRPC Proteins

    PubMed Central

    Blaustein, Mordecai P.; Hamlyn, John M.

    2010-01-01

    Salt retention as a result of chronic, excessive dietary salt intake, is widely accepted as one of the most common causes of hypertension. In a small minority of cases, enhanced Na+ reabsorption by the kidney can be traced to specific genetic defects of salt transport, or pathological conditions of the kidney, adrenal cortex, or pituitary. Far more frequently, however, the salt retention may be the result of minor renal injury or small genetic variation in renal salt transport mechanisms. How the salt retention actually leads to the increase in peripheral vascular resistance (the hallmark of hypertension) and the elevation of blood pressure remain an enigma. Here we review the evidence that endogenous ouabain (an adrenocortical hormone), arterial smooth muscle α2 Na+ pumps, type-1 Na/Ca exchangers, and receptor- and store-operated Ca2+ channels play key roles in the pathway that links salt to hypertension. We discuss cardenolide structure-function relationships in an effort to understand why prolonged administration of ouabain, but not digoxin, induces hypertension, and why digoxin is actually anti-hypertensive. Finally, we summarize recent observations which indicate that ouabain upregulates arterial myocyte Ca2+ signaling mechanisms that promote vasoconstriction, while simultaneously downregulating endothelial vasodilator mechanisms. In sum, the reports reviewed here provide novel insight into the molecular mechanisms by which salt retention leads to hypertension. PMID:20211726

  17. Renal tubular acidosis.

    PubMed

    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

  18. Effects of insulin and lipid emulsion on renal haemodynamics and renal sodium handling in IDDM patients.

    PubMed

    Pelikánová, T; Smrcková, I; Krízová, J; Stríbrná, J; Lánská, V

    1996-09-01

    To evaluate the role of insulin and hypertriglyceridaemia in the regulation of renal haemodynamics and sodium handling in insulin-dependent diabetes mellitus (IDDM), 11 IDDM patients without microalbuminuria and 13 weight-, age-, protein intake- and sex-matched healthy control subjects were studied. Clearances of inulin (Cin), para-amino-hippuric acid (CPAH), sodium (CNa), and lithium (CLi) were measured in four 60-min clearance periods (periods I, II, III and IV) during isoinsulinaemia with lipid emulsion infusion (study 1), a hyperinsulinaemic isoglycaemic clamp with Intralipid infusion (study 2), and during time-controlled isoinsulinaemia (study 3). We found that Cin, CPAH and filtration fraction were comparable in IDDM and control subjects, whereas CNa was decreased in diabetic subjects (2.01 +/- 1.11 vs 3.03 +/- 1.32 ml/min; p < 0.05) due to elevations of proximal tubular fractional and absolute reabsorptions of sodium (p < 0.05). Insulin infusion did not affect Cin, increased CPAH (p < 0.05) and, consequently, lowered the filtration fraction (p < 0.01) in both groups. While acute hyperinsulinaemia resulted in increases in distal tubular fractional and absolute reabsorptions of sodium (p < 0.01) contributing to a fall in CNa (p < 0.01) in control subjects, in diabetic subjects the sodium-retaining effect of insulin was not significant. The lipid emulsion did not alter any of the estimated parameters. We conclude that IDDM without microalbuminuria is associated with a tendency to sodium retention which is not aggravated by insulin when compared to control subjects. Acutely induced hypertriglyceridaemia does not alter renal haemodynamics or renal sodium handling.

  19. Reabsorption of Soft X-Ray Emission at High X-Ray Free-Electron Laser Fluences

    NASA Astrophysics Data System (ADS)

    Schreck, Simon; Beye, Martin; Sellberg, Jonas A.; McQueen, Trevor; Laksmono, Hartawan; Kennedy, Brian; Eckert, Sebastian; Schlesinger, Daniel; Nordlund, Dennis; Ogasawara, Hirohito; Sierra, Raymond G.; Segtnan, Vegard H.; Kubicek, Katharina; Schlotter, William F.; Dakovski, Georgi L.; Moeller, Stefan P.; Bergmann, Uwe; Techert, Simone; Pettersson, Lars G. M.; Wernet, Philippe; Bogan, Michael J.; Harada, Yoshihisa; Nilsson, Anders; Föhlisch, Alexander

    2014-10-01

    We report on oxygen K-edge soft x-ray emission spectroscopy from a liquid water jet at the Linac Coherent Light Source. We observe significant changes in the spectral content when tuning over a wide range of incident x-ray fluences. In addition the total emission yield decreases at high fluences. These modifications result from reabsorption of x-ray emission by valence-excited molecules generated by the Auger cascade. Our observations have major implications for future x-ray emission studies at intense x-ray sources. We highlight the importance of the x-ray pulse length with respect to the core-hole lifetime.

  20. Reabsorption of soft x-ray emission at high x-ray free-electron laser fluences.

    PubMed

    Schreck, Simon; Beye, Martin; Sellberg, Jonas A; McQueen, Trevor; Laksmono, Hartawan; Kennedy, Brian; Eckert, Sebastian; Schlesinger, Daniel; Nordlund, Dennis; Ogasawara, Hirohito; Sierra, Raymond G; Segtnan, Vegard H; Kubicek, Katharina; Schlotter, William F; Dakovski, Georgi L; Moeller, Stefan P; Bergmann, Uwe; Techert, Simone; Pettersson, Lars G M; Wernet, Philippe; Bogan, Michael J; Harada, Yoshihisa; Nilsson, Anders; Föhlisch, Alexander

    2014-10-10

    We report on oxygen K-edge soft x-ray emission spectroscopy from a liquid water jet at the Linac Coherent Light Source. We observe significant changes in the spectral content when tuning over a wide range of incident x-ray fluences. In addition the total emission yield decreases at high fluences. These modifications result from reabsorption of x-ray emission by valence-excited molecules generated by the Auger cascade. Our observations have major implications for future x-ray emission studies at intense x-ray sources. We highlight the importance of the x-ray pulse length with respect to the core-hole lifetime.

  1. Quantitative photoluminescence of broad band absorbing melanins: a procedure to correct for inner filter and re-absorption effects

    NASA Astrophysics Data System (ADS)

    Riesz, Jennifer; Gilmore, Joel; Meredith, Paul

    2005-07-01

    We report methods for correcting the photoluminescence emission and excitation spectra of highly absorbing samples for re-absorption and inner filter effects. We derive the general form of the correction, and investigate various methods for determining the parameters. Additionally, the correction methods are tested with highly absorbing fluorescein and melanin (broadband absorption) solutions; the expected linear relationships between absorption and emission are recovered upon application of the correction, indicating that the methods are valid. These procedures allow accurate quantitative analysis of the emission of low quantum yield samples (such as melanin) at concentrations where absorption is significant.

  2. MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition.

    PubMed

    Machackova, Tana; Mlcochova, Hana; Stanik, Michal; Dolezel, Jan; Fedorko, Michal; Pacik, Dalibor; Poprach, Alexandr; Svoboda, Marek; Slaby, Ondrej

    2016-11-01

    MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-β treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-β-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.

  3. Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma.

    PubMed

    Kusmartsev, Sergei; Eruslanov, Evgeniy; Kübler, Hubert; Tseng, Timothy; Sakai, Yoshihisa; Su, Zhen; Kaliberov, Sergei; Heiser, Axel; Rosser, Charles; Dahm, Philip; Siemann, Dietmar; Vieweg, Johannes

    2008-07-01

    Metastatic renal cell carcinoma (RCC) associates with overproduction of vascular endothelial growth factor (VEGF) due to the mutation/inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Herein we demonstrate that implantation of human RCC tumor cells into athymic nude mice promotes the appearance of VEGF receptor 1 (VEGFR1)/CD11b double-positive myeloid cells in peripheral blood. Avastin-mediated VEGF neutralization was capable of significantly reducing the numbers of circulating VEGFR1+ myeloid cells. Conversely, up-regulation of VEGFR1 by myeloid cells could also be achieved in vitro by coculturing bone marrow cells with RCC-conditioned medium or by short-term exposure of naive myeloid cells to oxidative stress. Treatment of myeloid cells with H2O2, lipid peroxidation product 4-hydroxy-2(E)-nonenal, or an inhibitor of thioredoxin reductase all resulted in increased expression of VEGFR1. Furthermore, after exposure to oxidative stress, myeloid cells acquire immunosuppressive features and become capable of inhibiting T cell proliferation. Data suggest that tumor-induced oxidative stress may promote both VEGFR1 up-regulation and immunosuppressive function in bone marrow-derived myeloid cells. Analysis of tumor tissue and peripheral blood from patients with metastatic RCC revealed that VEGFR1+ cells can be also found in cancer patients. Restoration of immunocompetence in metastatic RCC patients by pharmacological elimination of VEGFR1+ cells may have a significant impact on the therapeutic efficacy of cancer vaccines or other immune-based therapies.

  4. PI3Kβ inhibitor TGX221 selectively inhibits renal cell carcinoma cells with both VHL and SETD2 mutations and links multiple pathways.

    PubMed

    Feng, Chenchen; Sun, Yang; Ding, Guanxiong; Wu, Zhong; Jiang, Haowen; Wang, Lujia; Ding, Qiang; Wen, Hui

    2015-04-08

    We aimed to exploit novel compounds with high selectivity to clear cell renal cell carcinoma (ccRCC) with common mutations. Using the GDSC databases, we searched for compounds with high selectivity for ccRCC with VHL and/or SETD2 mutations. Clinical impact and gene interactions were analysed using TCGA database. In vitro and in vivo studies were performed to validate the inhibitory effects of the compound. We identified the selective PI3Kβ inhibitor TGX221 as a selective inhibitor for ccRCC with both VHL and SETD2 mutations. TGX221 also targeted cancer cells with CDKN2A and PTEN mutations. Changes in PTEN and CDKN2A gene sets were associated with worsened prognosis of ccRCC. TGX221 substantially and selectively inhibited the down stream products of VHL, SETD2, and PTEN in ccRCC cells with VHL and SETD2 mutations. TGX221 also exhibited significant selectivity in inhibiting cell motility and tumourigenesis of ccRCC cells with VHL and SETD2 mutations. TGX221 is a novel inhibitor with high selectivity for ccRCC with VHL and SETD2 mutations. It also targeted PTEN and CDKN2A mutations. How those genes were associated with PI3Kβ warranted further investigations.

  5. Postnatal development of renal function: micropuncture and clearance studies in the dog

    PubMed Central

    Horster, Michael; Valtin, Heinz

    1971-01-01

    Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes

  6. Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration.

    PubMed

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina; Birn, Henrik; Verroust, Pierre J; Nevéus, Tryggve; Sundelin, Birgitta; Hertz, Jens Michael; Holmström, Gerd; Ericson, Katharina; Christensen, Erik I; Nielsen, Rikke

    2013-03-01

    The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients. Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples. In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli. This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

  7. Comparative inhibition by hard and soft metal ions of steroid-binding capacity of renal mineralocorticoid receptor cross-linked to the 90-kDa heat-shock protein heterocomplex.

    PubMed Central

    Galigniana, M D; Piwien-Pilipuk, G

    1999-01-01

    We analysed the inhibitory effects in vitro and in vivo of several metal ions on aldosterone binding to the rat kidney mineralocorticoid receptor with the purpose of assessing possible toxic effects of those ions on sodium retention, as well as to obtain information on receptor structural requirements for ligand binding. For the assays in vitro, the inhibitory effects of 20 metal ions were analysed on steroid-binding capacity for renal receptor cross-linked to 90-kDa heat-shock protein (hsp90) by pretreatment with dimethyl pimelimidate. Cross-linking prevented the artifactual dissociation of hsp90 (and, consequently, the loss of steroid binding) from the mineralocorticoid receptor due to the presence of high concentrations of salt in the incubation medium. Cross-linked heterocomplex showed no difference in ligand specificity and affinity with respect to native receptor, but increased stability upon thermal- or ionic-strength-induced destabilization was observed. Treatments in vitro with metal ions in the range 10(-8)-10(-1) M resulted in a differential inhibitory effect for each particular ion on aldosterone binding. Using the negative logarithm of metal concentration for 50% inhibition, the ions could be correlated with their Klopman hardness constants. The analysis of this relationship led us to postulate three types of reaction: with thiol, imidazole and carboxyl groups. The essential role played by these residues in steroid binding was confirmed by chemical modification of cysteines with dithionitrobenzoic acid, histidines with diethyl pyrocarbonate and acidic amino acids with Woodward's reagent (N-ethyl-5-phenylisoxazolium-3'-sulphonate). Importantly, the toxic effects of some metal ions were also observed by treatments in vivo of adrenalectomized rats on both steroid-binding capacity and aldosterone-dependent sodium-retaining properties. We suggest that those amino acid residues are involved in the activation process of the mineralocorticoid receptor upon

  8. Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients.

    PubMed

    Stehling, Florian; Büscher, Rainer; Grosse-Onnebrink, Jörg; Hoyer, Peter F; Mellies, Uwe

    2017-01-01

    Introduction. Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1-57)) in a once-daily dosing regimen and 10 who did not. Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme.

  9. Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

    PubMed Central

    Büscher, Rainer; Grosse-Onnebrink, Jörg; Hoyer, Peter F.; Mellies, Uwe

    2017-01-01

    Introduction. Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1–57)) in a once-daily dosing regimen and 10 who did not. Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme. PMID:28133546

  10. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma

    PubMed Central

    KUROZUMI, AKIRA; KATO, MAYUKO; GOTO, YUSUKE; MATSUSHITA, RYOSUKE; NISHIKAWA, RIKA; OKATO, ATSUSHI; FUKUMOTO, ICHIRO; ICHIKAWA, TOMOHIKO; SEKI, NAOHIKO

    2016-01-01

    Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis. PMID:26983694

  11. Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer.

    PubMed

    Doyen, Jérôme; Carpentier, Xavier; Haudebourg, Juliette; Hoch, Benjamin; Karmous-Benailly, Houda; Ambrosetti, Damien; Fabas, Thibault; Amiel, Jean; Lambert, Jean-Claude; Pedeutour, Florence

    2012-11-01

    We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor (PPNET) located in the kidney was promptly excluded: Histologically, the tumor was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene rearrangement. The constitutional origin of this alteration was established. We report on the second case of RCC in a patient with a constitutional t(11;22). The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome. Our observation alerts cancer cytogeneticists to the fortuitous discovery of the constitutional t(11;22) in tumor cells. This translocation appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if present in all cells of a tumor other than PPNET. This is important when providing appropriate genetic counseling. Moreover, the potential oncogenic role of the t(11;22) and its predisposing risk of cancer are under debate. The family history of the patient revealed a disabled brother who died at an early age from colon cancer and a sister with breast cancer. This observation reopens the issue of a link between the constitutional t(11;22) and cancer, and the utility of cancer prevention workups for t(11;22) carriers. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Estrogen increases renal oxytocin receptor gene expression.

    PubMed

    Ostrowski, N L; Young, W S; Lolait, S J

    1995-04-01

    Estrogens have been implicated in the sodium and fluid imbalances associated with the menstrual cycle and late pregnancy. An estrogen-dependent role for renal oxytocin receptors in fluid homeostasis is suggested by the present findings which demonstrate that estradiol benzoate treatment increases the expression of the oxytocin receptor messenger ribonucleic acid and 125I-OTA binding to oxytocin receptors in the renal cortex and medullary collecting ducts of ovariectomized female rats. Moreover, estradiol induced high levels of oxytocin receptor expression in outer stripe proximal tubules of ovariectomized female and adrenalectomized male rats. Proximal tubule induction was inhibited in a dose-dependent manner by the antiestrogen tamoxifen, but cortical expression of oxytocin receptors in macula densa cells was unaffected by tamoxifen. These data demonstrate cell-specific regulation of oxytocin receptor expression in macula densa and proximal tubule cells, and suggest a important role for these receptors in mediating estrogen-induced alterations in renal fluid dynamics by possibly affecting glomerular filtration and water and solute reabsorption during high estrogen states.

  13. New molecular players facilitating Mg(2+) reabsorption in the distal convoluted tubule.

    PubMed

    Glaudemans, Bob; Knoers, Nine V A M; Hoenderop, Joost G J; Bindels, René J M

    2010-01-01

    The renal distal convoluted tubule (DCT) has an essential role in maintaining systemic magnesium (Mg(2+)) concentration. The DCT is the final determinant of plasma Mg(2+) levels, as the more distal nephron segments are largely impermeable to Mg(2+). In the past decade, positional candidate strategies in families with inherited forms of hypomagnesemia have led to the identification of genes involved in Mg(2+) handling. A large fraction of this resides in the DCT, namely, (i) the transient receptor potential channel melastatin subtype 6 (TRPM6), a divalent cation-permeable channel located at the luminal membrane of the DCT, facilitates Mg(2+) entry from the pro-urine into the cell; (ii) the epidermal growth factor is a novel hormone regulating active Mg(2+) transport through TRPM6; (iii) the voltage-gated K(+) channel, Kv1.1, establishes a favorable luminal membrane potential for TRPM6-mediated Mg(2+) transport; (iv) the Na(+)/K(+)-ATPase gamma-subunit (gamma-Na(+)/K(+)-ATPase) was identified as mutated protein in a family with isolated dominant hypomagnesemia. The molecular mechanism by which gamma-Na(+)/K(+)-ATPase is involved in DCT Mg(2+) handling remains unknown; (v) a high percentage of patients with mutations in the renal transcription factor HNF1B (hepatocyte nuclear factor 1 homeobox B) gene develop hypomagnesemia; and (vi) Gitelman and EAST/SeSAME syndrome patients suffer from a similar tubulopathy due to mutations in NCC (NaCl cotransporter) and Kir4.1, respectively. In these patients, decreased expression of TRPM6 is proposed to cause hypomagnesemia. Insights into the molecular mechanisms of the identified genes, as well as the identification of novel genes, will further improve our knowledge about renal Mg(2+) handling.

  14. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  15. Renal drug transporters and their significance in drug-drug interactions.

    PubMed

    Yin, Jia; Wang, Joanne

    2016-09-01

    The kidney is a vital organ for the elimination of therapeutic drugs and their metabolites. Renal drug transporters, which are primarily located in the renal proximal tubules, play an important role in tubular secretion and reabsorption of drug molecules in the kidney. Tubular secretion is characterized by high clearance capacities, broad substrate specificities, and distinct charge selectivity for organic cations and anions. In the past two decades, substantial progress has been made in understanding the roles of transporters in drug disposition, efficacy, toxicity and drug-drug interactions (DDIs). In the kidney, several transporters are involved in renal handling of organic cation (OC) and organic anion (OA) drugs. These transporters are increasingly recognized as the target for clinically significant DDIs. This review focuses on the functional characteristics of major human renal drug transporters and their involvement in clinically significant DDIs.

  16. Reduced reabsorption and enhanced propagation induced by large Stokes shift in quantum dot-filled optical fiber

    NASA Astrophysics Data System (ADS)

    Wu, Hua; Zhang, Yu; Lu, Min; Liu, Wenyan; Xu, Jian; Yu, William W.

    2016-07-01

    With tunable emission wavelength, high photoluminescence quantum yield, and broad absorption, colloidal quantum dots are attractive for the application in optical fiber as dopants. However, most of the quantum dots have a large overlap between their absorption and photoluminescence spectra, resulting in reabsorption loss which hinders the realization of long-distance waveguides. Therefore, ZnCuInS/ZnSe/ZnS quantum dots with large Stokes shift were proposed to fabricate a liquid-core optical fiber in this work. In this work, ZnCuInS/ZnSe/ZnS QDs with an average size of 3.3 nm were synthesized and the optical properties of the QD-filled fiber were also investigated as a function of fiber length and doping concentration. Compared to the control sample filled with CdSe/CdS/ZnS quantum dots, the ZnCuInS/ZnSe/ZnS quantum dot-based waveguides showed reduced reabsorption and enhanced signal propagation, which demonstrates great potential of large Stokes-shift quantum dots in optical waveguide devices.

  17. MDCK cells are capable of water secretion and reabsorption in response to changes in the ionic environment.

    PubMed

    Capra, Janne P; Eskelinen, Sinikka M

    2017-01-01

    A prerequisite for tissue electrolyte homeostasis is highly regulated ion and water transport through kidney or intestinal epithelia. In the present work, we monitored changes in the cell and luminal volumes of type II Madin-Darby canine kidney (MDCK) cells grown in a 3D environment in response to drugs, or to changes in the composition of the basal extracellular fluid. Using fluorescent markers and high-resolution spinning disc confocal microscopy, we could show that lack of sodium and potassium ions in the basal fluid (tetramethylammonium chloride (TMACl) buffer) induces a rapid increase in the cell and luminal volumes. This transepithelial water flow could be regulated by inhibitors and agonists of chloride channels. Hence, the driving force for the transepithelial water flow is chloride secretion, stimulated by hyperpolarization. Chloride ion depletion of the basal fluid (using sodium gluconate buffer) induces a strong reduction in the lumen size, indicating reabsorption of water from the lumen to the basal side. Lumen size also decreased following depolarization of the cell interior by rendering the membrane permeable to potassium. Hence, MDCK cells are capable of both absorption and secretion of chloride ions and water; negative potential within the lumen supports secretion, while depolarizing conditions promote reabsorption.

  18. [Thyroxine treatment in acute renal failure (author's transl)].

    PubMed

    Straub, E

    1975-11-01

    8 patients suffering from acute renal failure (shock kidney) with anuria extending over 3 to 5 days, were treated with L-thyroxine for 5 to 9 days (5-6 mug per kg body weight per day orally). Diuresis was restored within 34 to 46 hrs. Plasma levels of urea and creatinine decreased earlier and much more rapidly to normal than was to be expected from the natural history of the disease, indicating the prompt and extensive increase of glomerular filtration rate. Polyuria seemed less pronounced and also shortened as compared with the ordinary course of that form of sudden renal insufficiency. Obviously, the well-known diuretic response in the normal individual to high doses of thyroid hormones in not a factor in the induction of diuresis in acute renal failure. The tendency with L-thyroxine treatment to dilate the preglomerular arterial vessel is considered a consequence of the stimulation of sodium reabsorption in the upper nephron. High values of RPF and GFR, regularly observed in hyperthyroidism or after L-thyroxine administration, do not depend on any augmentation of cardiac output or on arterial hypertension, since such symptoms were missed in our patients and, in our view, such an interpretation is excluded by the very existence of the so-called autoregulation of the kidney which leaves RPF (and therefore GFR) independent of systemic blood pressure. The same intrarenal feed-back mechanism, normally adapting the glomerular blood supply to the resorptive capacity of the proximal-tubular epithelium (mediation via the juxta-glomerular apparatus), is responsible for the GFR- and RPF-raising effect of exogenous L-thyroxine in the intact kidney as well as in acute renal failure: both sodium reabsorption and sodium filtration are accelerated.--The special conditions under which L-thyroxine interferes with the pathogenetic process of acute renal failure, the latter being characterised by the critical insufficiency of tubular sodium reabsorption and therefore by

  19. Regulation of ENaC-Mediated Sodium Reabsorption by Peroxisome Proliferator-Activated Receptors

    PubMed Central

    Pavlov, Tengis S.; Imig, John D.; Staruschenko, Alexander

    2010-01-01

    Peroxisome proliferator-activated receptors (PPARs) are members of a steroid hormone receptor superfamily that responds to changes in lipid and glucose homeostasis. Peroxisomal proliferator-activated receptor subtype γ (PPARγ) has received much attention as the target for antidiabetic drugs, as well as its role in responding to endogenous compounds such as prostaglandin J2. However, thiazolidinediones (TZDs), the synthetic agonists of the PPARγ are tightly associated with fluid retention and edema, as potentially serious side effects. The epithelial sodium channel (ENaC) represents the rate limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector impacting systemic blood volume and pressure. The role of PPARγ agonists on ENaC activity remains controversial. While PPARγ agonists were shown to stimulate ENaC-mediated renal salt absorption, probably via Serum- and Glucocorticoid-Regulated Kinase 1 (SGK1), other studies reported that PPARγ agonist-induced fluid retention is independent of ENaC activity. The current paper provides new insights into the control and function of ENaC and ENaC-mediated sodium transport as well as several other epithelial channels/transporters by PPARs and particularly PPARγ. The potential contribution of arachidonic acid (AA) metabolites in PPAR-dependent mechanisms is also discussed. PMID:20613963

  20. Blood Pressure and the Renal Actions of AT2 Receptors.

    PubMed

    Carey, Robert M

    2017-03-01

    Angiotensin type-2 receptors (AT2Rs) in the renal proximal tubule inhibit sodium (Na+) reabsorption by inducing renal cyclic GMP formation and internalizing and inhibiting major Na+ transporters Na+-H+ exchanger-3 (NHE-3) and Na+/K+ATPase (NKA). Instead of angiotensin II (Ang II), angiotensin III (Ang III) is the predominant endogenous agonist for this response. Exogenous non-peptide AT2R agonist Compound-21 induces natriuresis and lowers blood pressure (BP) in normal and Ang II-infused hypertensive rodents. Spontaneously hypertensive rats (SHR; both pre-hypertensive and hypertensive) have defective natriuretic responses to Ang III, suggesting a defect in AT2R-mediated natriuresis in SHR that leads to hypertension. The mechanisms of deficient AT2R-mediated natriuresis in SHR are unknown but could involve either pre-receptor or receptor/post-receptor defects.

  1. Assessment of renal function in workers previously exposed to cadmium.

    PubMed Central

    Elinder, C G; Edling, C; Lindberg, E; Kågedal, B; Vesterberg, O

    1985-01-01

    Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate. PMID:3904816

  2. Renal threshold phosphate concentration (TmPO4/GFR).

    PubMed Central

    Kruse, K; Kracht, U; Göpfert, G

    1982-01-01

    The ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO4/GFR) was determined in 546 schoolchildren, aged between 6 and 17.9 years, using the nomogram of Walton and Bijvoet.1 TmPO4/GFR correlated with chronological age in girls and boys and in each remained significantly higher than in adults. TmPO4/GFR in the children correlated neither with fasting serum immunoreactive calcitonin and parathyroid hormone levels nor with the urinary cyclic AMP excretion. The study showed a parallel decrease in TmPO4/GFR, excretion of total hydroxyproline and serum alkaline phosphatase activities after puberty, with a significant relationship of both these indices of bone turnover to TmPO4/GFR values. This indicates that the high renal phosphate threshold of children may be an important factor for bone mineralisation by providing high extracellular inorganic phosphate concentrations during normal growth. PMID:6280622

  3. Renal Scintigraphy

    MedlinePlus

    ... size with caption Related Articles and Media General Nuclear Medicine Radiation Dose in X-Ray and CT Exams X-ray, Interventional Radiology and Nuclear Medicine Radiation Safety Images related to Renal Scintigraphy Sponsored by ...

  4. Renal handling of terephthalic acid

    SciTech Connect

    Tremaine, L.M.; Quebbemann, A.J.

    1985-01-01

    By use of the Sperber in vivo chicken preparation method, infusion of radiolabeled terephthalic acid ((/sup 14/C)TPA) into the renal portal circulation revealed a first-pass excretion of the unchanged compound into the urine. This model was utilized further to characterize the excretory transport of (/sup 14/C)TPA and provide information on the structural specificity in the secretion of dicarboxylic acids. At an infusion rate of 0.4 nmol/min. 60% of the (/sup 14/C)TPA which reached the kidney was directly excreted. An infusion rate of 3 or 6 mumol/min resulted in complete removal of (/sup 14/C)TPA by the kidney. These results indicate that TPA is both actively secreted and actively reabsorbed when infused at 0.4 nmol/min and that active reabsorption is saturated with the infusion of TPA at higher concentrations. The secretory process was saturated with the infusion of TPA at 40 mumol/mn. The excretory transport of TPA was inhibited by the infusion of probenecid, salicylate, and m-hydroxybenzoic acid, indicating that these organic acids share the same organic anion excretory transport process. m-Hydroxybenzoic acid did not alter the simultaneously measured excretory transport of p-aminohippuric acid (PAH), suggesting that there are different systems involved in the secretion of TPA and PAH. The structural specificity for renal secretion of dicarboxylic acids was revealed by the use of o-phthalic acid and m-phthalic acid as possible inhibitors of TPA secretion.

  5. Photon Emission and Reabsorption Processes in CH3NH3PbBr3 Single Crystals Revealed by Time-Resolved Two-Photon-Excitation Photoluminescence Microscopy

    NASA Astrophysics Data System (ADS)

    Yamada, Takumi; Yamada, Yasuhiro; Nakaike, Yumi; Wakamiya, Atsushi; Kanemitsu, Yoshihiko

    2017-01-01

    The dynamical processes of radiative recombination of photocarriers and reabsorption of emitted photons in CH3NH3PbBr3 single crystals are studied using time-resolved two-photon-excitation photoluminescence (PL) microscopy. We find that the PL spectrum and its decay dynamics depend on the excitation-depth profile. As the excitation depth increases, the PL spectrum becomes asymmetric, the peak energy redshifts, and the PL decay time becomes longer. These observations can be well explained by a simple model including photon recycling (photon emission and reabsorption) in thick samples with strong band-to-band transitions and high radiative recombination efficiencies.

  6. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney.

    PubMed

    Graceli, J B; Cicilini, M A; Bissoli, N S; Abreu, G R; Moysés, M R

    2013-06-01

    The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg · kg(-1) · day(-1), sc) and progesterone (OVP, 1.7 mg · kg(-1) · day(-1), sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6 ± 36.1 ng/g) and denervated rat groups (D: 102.1 ± 15.7; ODE: 108.7 ± 23.2; ODP: 101.1 ± 22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9 ± 25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

  7. Future of the Renal Biopsy: Time to Change the Conventional Modality Using Nanotechnology

    PubMed Central

    Khosroshahi, Hamid Tayebi; Sarbaz, Yashar; Shakeri Bavil, Abolhassan

    2017-01-01

    At the present time, imaging guided renal biopsy is used to provide diagnoses in most types of primary and secondary renal diseases. It has been claimed that renal biopsy can provide a link between diagnosis of renal disease and its pathological conditions. However, sometimes there is a considerable mismatch between patient renal outcome and pathological findings in renal biopsy. This is the time to address some new diagnostic methods to resolve the insufficiency of conventional percutaneous guided renal biopsy. Nanotechnology is still in its infancy in renal imaging; however, it seems that it is the next step in renal biopsy, providing solutions to the limitations of conventional modalities. PMID:28316612

  8. Renal abnormalities in patients with Kallmann syndrome.

    PubMed

    Zenteno, J C; Méndez, J P; Maya-Núñez, G; Ulloa-Aguirre, A; Kofman-Alfaro, S

    1999-03-01

    To report experience in patients with Kallmann syndrome (KS) in whom urography was used to establish the type and frequency of renal anomalies associated with the disorder. Of 19 patients with KS, 15 had the X-linked recessive form of the disease, whereas the remaining four were sporadic. Each patient underwent intravenous pyelography (IVP) using a non-ionic, low osmolarity contrast medium. Of the 19 patients with KS, 10 had kidney abnormalities; four presented with unilateral renal agenesis and six had less severe forms of renal abnormality (renal malrotation in four and bilateral dilatation of the calyces and pelves in two). One of the patients with unilateral renal agenesis carried a deletion in KAL, the gene responsible for the X-linked type of KS. Three of the four patients with renal malrotation had a confirmed X-linked recessive form and one carried a point mutation in KAL. These results suggest that kidney abnormalities are more frequent and diverse in patients with KS than previously reported. They also indicate that defects in the KAL gene may contribute to abnormal renal development. However, a review of the literature revealed no close correlation between KAL mutations and kidney anomalies in the X-linked type of disease. Taken together, these data suggest that KAL mutations are not invariably associated with failure of renal development and that additional factors (epigenetic or local) may compensate for defects in the KAL protein.

  9. cDNA cloning of the murine PEX gene implicated in X-linked hypophosphatemia and evidence for expression in bone

    SciTech Connect

    Du, L.; Desbarats, M.; Viel, J.

    1996-08-15

    The recently identified human PEX g ene apparently encodes for a neutral endopeptidase that is mutated in patients with X-linked hypophosphatemia. The 3{prime} and 5{prime} ends of the coding region of PEX have not been cloned, nor has the tissue expression of the gene been identified. Here we report the isolation and characterization of the complete open reading frame of the mouse Pex gene and the demonstration of its expression in bone. Mouse Pex cDNA is predicted to encode a protein of 749 amino acids with 95% identity to the available human PEX sequence and significant homology to members of the membrane-bound metalloendopeptidase family. Northern blot analysis revealed a 6.6-kb transcript in bone and in cultured osteoblasts from normal mice that was not detectable in samples from the Hyp mouse, the murine homolog of human X-linked hypophosphatemia. Pex transcripts were, however, detectable in Hyp bone by RT-PCR amplification. Of particular interest, a cDNA clone from rat incisor shows 93% sequence identity to the 5{prime} end of Pex cDNA, suggesting that Pex may be expressed in another calcified tissue, the tooth. The association of impaired mineralization of bone and teeth and disturbed renal phosphate reabsorption with altered expression of Pex suggests that the Pex gene product may play a critical role in these processes. 47 refs., 2 figs., 1 tab.

  10. Role of adenosine in tubuloglomerular feedback and acute renal failure.

    PubMed

    Osswald, H; Vallon, V; Mühlbauer, B

    1996-12-01

    1. Adenosine (ADO) can induce renal vasoconstriction and a fall in glomerular filtration rate. When the rate of ATP hydrolysis prevails over the rate of ATP synthesis the kidney generates ADO at an enhanced rate. 2. Tubuloglomerular feedback (TGF) is the vascular response to changes of the NaCl concentration in the tubular fluid at the macula densa segment, which is the result of transepithelial electrolyte reabsorption by the proximal tubule and the loop of Henle. 3. TGF can be inhibited by ADO-A1 receptor antagonists and is potentiated by substances that can elevate extracellular ADO concentrations. These observations led to the hypothesis that ADO is an element of the signal transmission processes in the juxtaglomerular apparatus. 4. Renal ischaemia and nephrotoxic substances can induce acute renal failure (ARF). ADO receptor antagonists have been shown to ameliorate renal function in several different models of ARF in laboratory animals and humans. 5. A number of factors, such as extracellular volume contraction, low NaCl diet, angiotensin II and cyclooxygenase inhibitors enhance to a similar extent: (a) the renal vascular response to endogenous and exogenous ADO; (b) the TGF response of the nephron; and (c) the severity of ARF. All three phenomena are susceptible to antagonism by ADO receptor antagonists. 6. Therefore, we conclude that ADO plays a significant role in normal and pathological states of kidney function.

  11. Pressure natriuresis and the renal control of arterial blood pressure

    PubMed Central

    Ivy, Jessica R; Bailey, Matthew A

    2014-01-01

    The regulation of extracellular fluid volume by renal sodium excretion lies at the centre of blood pressure homeostasis. Renal perfusion pressure can directly regulate sodium reabsorption in the proximal tubule. This acute pressure natriuresis response is a uniquely powerful means of stabilizing long-term blood pressure around a set point. By logical extension, deviation from the set point can only be sustained if the pressure natriuresis mechanism is impaired, suggesting that hypertension is caused or sustained by a defect in the relationship between renal perfusion pressure and sodium excretion. Here we describe the role of pressure natriuresis in blood pressure control and outline the cascade of biophysical and paracrine events in the renal medulla that integrate the vascular and tubular response to altered perfusion pressure. Pressure natriuresis is impaired in hypertension and mechanistic insight into dysfunction comes from genetic analysis of blood pressure disorders. Transplantation studies in rats show that blood pressure is determined by the genotype of the kidney and Mendelian hypertension indicates that the distal nephron influences the overall natriuretic efficiency. These approaches and the outcomes of genome-wide-association studies broaden our view of blood pressure control, suggesting that renal sympathetic nerve activity and local inflammation can impair pressure natriuresis to cause hypertension. Understanding how these systems interact is necessary to tackle the global burden of hypertension. PMID:25107929

  12. Impaired renal function and development in Belgrade rats

    PubMed Central

    Veuthey, Tania; Hoffmann, Dana; Vaidya, Vishal S.

    2013-01-01

    Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID:24226520

  13. Pressure natriuresis and the renal control of arterial blood pressure.

    PubMed

    Ivy, Jessica R; Bailey, Matthew A

    2014-09-15

    The regulation of extracellular fluid volume by renal sodium excretion lies at the centre of blood pressure homeostasis. Renal perfusion pressure can directly regulate sodium reabsorption in the proximal tubule. This acute pressure natriuresis response is a uniquely powerful means of stabilizing long-term blood pressure around a set point. By logical extension, deviation from the set point can only be sustained if the pressure natriuresis mechanism is impaired, suggesting that hypertension is caused or sustained by a defect in the relationship between renal perfusion pressure and sodium excretion. Here we describe the role of pressure natriuresis in blood pressure control and outline the cascade of biophysical and paracrine events in the renal medulla that integrate the vascular and tubular response to altered perfusion pressure. Pressure natriuresis is impaired in hypertension and mechanistic insight into dysfunction comes from genetic analysis of blood pressure disorders. Transplantation studies in rats show that blood pressure is determined by the genotype of the kidney and Mendelian hypertension indicates that the distal nephron influences the overall natriuretic efficiency. These approaches and the outcomes of genome-wide-association studies broaden our view of blood pressure control, suggesting that renal sympathetic nerve activity and local inflammation can impair pressure natriuresis to cause hypertension. Understanding how these systems interact is necessary to tackle the global burden of hypertension.

  14. An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis.

    PubMed

    Morris, R C

    1968-07-01

    In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO(3) (-)) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO(3) (-)) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO(3) (-) of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H(+) secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO(3) (-) (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid.A reduced H(+) secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO(3) (-) was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal.

  15. On the mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (type 2 RTA)

    PubMed Central

    Sebastian, Anthony; McSherry, Elisabeth; Morris, R. Curtis

    1971-01-01

    The mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (type 2 RTA) was investigated in 10 patients, each of whom had impaired proximal renal tubular reabsorption of bicarbonate as judged from a greater than 15-20% reduction of renal tubular bicarbonate reabsorption (THCO3-) at normal plasma bicarbonate concentrations. When the plasma bicarbonate concentration ([HCO3-]p) was experimentally increased to normal levels in three patients with a fractional potassium excretion (CK/Cin) of less than 1.0 during acidosis, CK/Cin and urinary potassium excretion (UKV/Cin) increased strikingly and concurrently with a striking increase in urinary sodium (UNaV/Cin) and bicarbonate (UHCO3-V/Cin) excretion. When [HCO3-]p was increased to normal levels in two patients with a CK/Cin of greater than 1.0 during acidosis and in whom UNaV/Cin and UHCO3-V/Cin were already markedly increased, CK/Cin did not increase further. When [HCO3-]p was decreased to subnormal levels in a patient given ammonium chloride, UKV/Cin, CK/Cin, and UHCO3-V/Cin decreased concurrently. In the six patients in whom [HCO3-]p was maintained at normal levels (oral alkali therapy) for 2 months or longer, CK/Cin was directly related to the urinary excretion rates of sodium and bicarbonate, hence was directly related to the magnitude of reduction of THCO3- at normal [HCO3-]p; CK/Cin was greater than 0.55 in all six patients and greater than 1.0 in four. In eight patients with classic RTA (type 1 RTA), proximal renal tubular reabsorption of bicarbonate was largely intact as judged from a trivial reduction of THCO3- at normal [HCO3-]p. When [HCO3-]p was either increased from subnormal to normal levels, or decreased from normal to subnormal levels, UHCO3-V/Cin remained essentially constant, and UKV/Cin did not change significantly. When correction of acidosis was sustained, UHCO3-V/Cin remained a trivial fraction of that filtered, and CK/Cin was consistently less than 0

  16. Carbonic anhydrases in chick extra-embryonic structures: a role for CA in bicarbonate reabsorption through the chorioallantoic membrane.

    PubMed

    Gabrielli, M Gabriella

    2004-06-01

    The villus cavity cells, a specific cell type of the chick chorioallantoic membrane, express both cytosolic carbonic anhydrase in their cytoplasm and HCO3(-)/Cl(-) anion exchangers at their basolateral membranes. By immunohistochemical analysis, we show here that villus cavity cells specifically react with antibodies directed against the membrane-associated form of carbonic anhydrase, CAIV. Staining is restricted to the apical cell membranes, characteristically invaginated toward the shell membrane, as well as to endothelia of blood vessels present in the mesodermal layer. The occurrence of a membrane-associated CA form at the apical pole of villus cavity cells, when definitively confirmed, would be fairly consistent with the role proposed for these cells in bicarbonate reabsorption from the eggshell so to prevent metabolic acidosis in the embryo during development.

  17. Luminescent solar concentrators. I. Concentrators based on mixtures of dyes in PMMA. Spectral and luminescent properties, reabsorption and energy transfer

    NASA Astrophysics Data System (ADS)

    Svetlichnyi, V. A.; Lapin, I. N.; Vaitulevich, E. A.; Biryukov, A. A.

    2013-07-01

    Spectral and luminescent properties of efficient and stable commercial organic dyes in solutions and polymethylmetacrilate (PMMA), absorbing and emitting in wavelength ranges 300-680 nm and 390-750 nm, respectively, are investigated. Using different excitation and registration schemes, it is demonstrated that spectral shifts of initial radiation caused by reabsorption are observed at wavelengths around 1.5 cm. The process of excitation energy transfer from the UV range to the red range of the spectrum is investigated in mixtures of 4-6 dyes of different compositions. The maximum efficiency of radiation transfer from 300 nm to 560-580 nm, exceeding the efficiency of individual fluorophores by a factor of >1.6 is obtained for mixtures of four dyes POPOP(bis-MSB)-Coumarin 30-DCM-Pyrromethene 580 (Rhodamine 11B) in PMMA.

  18. Renal manifestations of primary mitochondrial disorders.

    PubMed

    Finsterer, Josef; Scorza, Fulvio Alexandre

    2017-05-01

    The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or malign neoplasms. Among the syndromic MIDs, renal involvement has been most frequently reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh syndrome and mitochondrial depletion syndromes. Only in single cases was renal involvement also reported in chronic progressive external ophthalmoplegia, Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X-linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis syndrome. The present study proposes that the frequency of renal involvement in MIDs is probably underestimated. Diagnosis of renal involvement follows general guidelines and treatment is symptomatic. Thus, renal manifestations of primary MIDs require recognition and appropriate management, as they determine the outcome of MID patients.

  19. Renal manifestations of primary mitochondrial disorders

    PubMed Central

    Finsterer, Josef; Scorza, Fulvio

    2017-01-01

    The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or malign neoplasms. Among the syndromic MIDs, renal involvement has been most frequently reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh syndrome and mitochondrial depletion syndromes. Only in single cases was renal involvement also reported in chronic progressive external ophthalmoplegia, Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X-linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis syndrome. The present study proposes that the frequency of renal involvement in MIDs is probably underestimated. Diagnosis of renal involvement follows general guidelines and treatment is symptomatic. Thus, renal manifestations of primary MIDs require recognition and appropriate management, as they determine the outcome of MID patients. PMID:28515908

  20. Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2).

    PubMed

    Kawamura, Y; Matsuo, H; Chiba, T; Nagamori, S; Nakayama, A; Inoue, H; Utsumi, Y; Oda, T; Nishiyama, J; Kanai, Y; Shinomiya, N

    2011-12-01

    Renal hypouricemia (MIM 220150) is an inherited disorder characterized by low serum uric acid levels and has severe complications such as exercise-induced acute renal failure and urolithiasis. We have previously reported that URAT1/SLC22A12 encodes a renal urate-anion exchanger and that its mutations cause renal hypouricemia type 1 (RHUC1). With the large health-examination database of the Japan Maritime Self-Defense Force, we found two missense mutations (R198C and R380W) of GLUT9/SLC2A9 in hypouricemia patients. R198C and R380W occur in highly conserved amino acid motifs in the "sugar transport proteins signatures" that are observed in GLUT family transporters. The corresponding mutations in GLUT1 (R153C and R333W) are known to cause GLUT1 deficiency syndrome because arginine residues in this motif are reportedly important as the determinants of the membrane topology of human GLUT1. Therefore, on the basis of membrane topology, the same may be true of GLUT9. GLUT9 mutants showed markedly reduced urate transport in oocyte expression studies, which would be the result of the loss of positive charges in those conserved amino acid motifs. Together with previous reports on GLUT9 localization, our findings suggest that these GLUT9 mutations cause renal hypouricemia type 2 (RHUC2) by their decreased urate reabsorption on both sides of the renal proximal tubule cells. However, a previously reported GLUT9 mutation, P412R, was unlikely to be pathogenic. These findings also enable us to propose a physiological model of the renal urate reabsorption via GLUT9 and URAT1 and can lead to a promising therapeutic target for gout and related cardiovascular diseases.

  1. Protective Role of Apelin Against Cyclosporine-Induced Renal Tubular Injury in Rats.

    PubMed

    Kim, J S; Yang, J W; Han, B G; Kwon, H J; Kim, J H; Choi, S O

    Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection. We performed serum and urinary assays of creatinine and neutrophil gelatinase-associated lipocalin (NGAL) to estimate renal injury and performed Western blotting for endothelial nitric oxide synthase and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) to document the underlying mechanism. The CsA-treated group showed increased urinary creatinine excretion, polyuria, and renal glycosuria without GFR reduction, suggesting adequate CsA-induced renal tubular injury. Urinary NGAL excretion also increased significantly in the CsA group. Conversely, apelin attenuated CsA-induced tubular injury and had no effect on urinary NGAL excretion. In histopathologic examination, the apelin-treated group had lower tubulo-interstitial injury scores compared with those in the CsA group. Regarding the effects of apelin, our results indicate that apelin provides protection against CsA-induced tubular injury by activating nitric oxide and/or the NFATc1 pathway. Notably, we also found that CsA inhibits renal glucose reabsorption by reducing Na(+)-K(+) ATPase expression and that apelin reverses reduced renal glucose reabsorption by CsA in tubular cells. Our study demonstrates the renoprotective effect of apelin against CsA-induced renal tubular toxicity and provides novel insights into the effects of CsA and apelin on renal tubular cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Reabsorption of yellow fluorescent protein in the Rana temporaria kidney by receptor-mediated endocytosis].

    PubMed

    Seliverstova, E V; Prutskova, N P

    2014-01-01

    The absorption of yellow fluorescent protein (YFP) and the expression of the endocytic receptors, megalin and cubilin, were investigated in the renal proximal tubules (PT) in frogs Rana temporaria after parenteral YFP injections. The methods of confocal microscopy and immunohistochemistry were used. The dynamics of YFP absorption was analyzed 2 h after injection. The logarithmic time dependence of the accumulation of YFP-containing endocytic vesicles in PT cells and the completion of absorption process 90-120 min after injection were shown. Unlike substantial megalin and cubilin expression 15-30 min after YFP introduction, immunolabeled endocytic receptors were not detected in PT cells after 2 h. The re-injection of YFP led to the appearance of apical endocytic vesicles containing megalin or cubilin colocalized with YFP. At the same time, the decrease of YFP uptake associated with reduction in the number of receptor-containing vesicles was demonstrated, suggesting a failure of megalin and cubilin expression. The decrease of absorption capacity of PT cells after YFP re-injection was similar to that found previously under conditions of the competitive absorption of green fluorescent protein (GFP) and YFP injected in different sequences. The data are the further demonstration of the proposed mechanism limiting the tubular protein absorption in the frog kidney and suggest the involvement of megalin and cubilin in uptake and vesicular transport of YFP.

  3. Managing new-onset gout in pediatric renal transplant recipients: when, how, to what extent.

    PubMed

    Assadi, Farahnak

    2013-01-01

    Hyperuricemia and gout are common among adult renal transplant recipients, but it is rarely reported following pediatric renal transplantations. Treating gout in pediatric kidney transplant recipients presents clinical challenges to the management of both immunosuppressive regimen and hyperuricemia for their effects on serum uric acid levels, renal function and drug interactions. Most renal transplant recipients have a relative impairment of renal clearance of urate due to abnormalities in renal transport, explaining the association of hyperuricemia and decreased glomerular filtration rate. Risk factors for the development of gout include impaired renal function, hypertension, heart failure and diabetes mellitus. Calcineurin inhibitors, particularly cyclosporine, are the most important risk factor for gout in transplant recipients and should not be used in pediatric renal transplant recipients. Diuretic therapy increases the risk of gout by causing extracellular volume contraction with consequent enhancement of proximal tubular reabsorption. Corticosteroids are increasingly replacing nonsteroidal antiinflammatory drugs and colchicine for the treatment of acute gout flares because they have little effect on kidney function. Proper management is aimed at lowering serum uric acid level below 6.0 mg/dL with xanthine oxidase inhibitors such as allopurinol or febuxostat. Allopurinol and mycophenolate mofetil are safer to use in combination than are allopurinol and azathioprine. Febuxostat is an alternative to allopurinol in patients with allopurinol intolerance or hypersensitivity. Pegloticase is indicated for patients with severe gout in whom allopurinol and febuxostat have not been effective or tolerated.

  4. Effect of carotid occlusion and of perfusion pressure on renal function in conscious dogs.

    PubMed

    Gross, R; Kirchheim, H; Ruffmann, K

    1981-06-01

    We studied the effect of bilateral common carotid occlusion (implanted pneumatic cuffs) on renal blood flow (electromagnetic flowmeter) and renal function (implanted ureteral catheter) in nine chronically instrumented, conscious dogs on a high sodium diet (14 mmol/kg body weight per day). By means of suprarenal aortic constriction (pneumatic cuff) the influence of renal perfusion pressure was investigated. There was no change in renal blood flow or glomerular filtration rate (inulin clearance) with either reflexly increasing (+49.6%) or constant renal perfusion pressure. Carotid occlusion caused an increase of urine output by 80.5% and of sodium excretion by 85.3% due to a fall in fractional sodium reabsorption (-0.9%) when renal perfusion pressure was allowed to rise. Neither an increase of diuresis or sodium excretion nor an antinatriuresis was observed when renal perfusion pressure was kept constant during carotid occlusion. We conclude that, in conscious dogs at rest, the moderate sympathetic activation associated with carotid occlusion is too small to induce renal sympathetic vasoconstriction or antinatriuresis. The "carotid sinus polyuria" is a pressure-diuresis.

  5. Effect of chronic alcohol feeding on physiological and molecular parameters of renal thiamin transport.

    PubMed

    Subramanian, Veedamali S; Subramanya, Sandeep B; Tsukamoto, Hidekazu; Said, Hamid M

    2010-07-01

    The renal thiamin reabsorption process plays an important role in regulating thiamin body homeostasis and involves both thiamin transporters-1 and -2 (THTR1 and THTR2). Chronic alcohol use is associated with thiamin deficiency. Although a variety of factors contribute to the development of this deficiency, effects of chronic alcohol use on renal thiamin transport have not been thoroughly examined. We addressed this issue by examining the effect of chronic alcohol feeding of rats with liquid diet on physiological and molecular parameters of renal thiamin transport. Chronic alcohol feeding caused a significant inhibition in carrier-mediated thiamin transport across the renal brush-border membrane and was evident as early as 2 wk after initiation of alcohol feeding. Similarly, thiamin transport across the renal basolateral membrane was significantly inhibited by chronic alcohol feeding. The inhibition in renal thiamin transport was associated with a marked decrease in the level of expression of THTR1 and -2 proteins, mRNAs, and heterogeneous nuclear RNAs. Chronic alcohol feeding also caused a significant reduction in the level of expression of thiamin pyrophosphokinase but not that of the mitochondrial thiamin pyrophosphate transporter. These studies show that chronic alcohol feeding inhibits the entry and exit of thiamin in the polarized renal epithelial cells and that the effect is, at least in part, mediated at the transcriptional level. These findings also suggest that chronic alcohol feeding interferes with the normal homeostasis of thiamin in renal epithelial cells.

  6. The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease.

    PubMed

    Sata, Yusuke; Schlaich, Markus P

    2016-07-01

    Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

  7. The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

    PubMed

    Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

    2015-04-20

    What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  8. Determination of the maximum rate of eccrine sweat glands’ ion reabsorption using the galvanic skin conductance to local sweat rate relationship.

    PubMed

    Amano, Tatsuro; Gerrett, Nicola; Inoue, Yoshimitsu; Nishiyasu, Takeshi; Havenith, George; Kondo, Narihiko

    2016-02-01

    The purpose of the present study was to develop and describe a simple method to evaluate the rate of ion reabsorption of eccrine sweat glands in human using the measurement of galvanic skin conductance (GSC) and local sweating rate (SR). This purpose was investigated by comparing the SR threshold for increasing GSC with following two criteria of sweat ion reabsorption in earlier studies such as (1) the SR threshold for increasing sweat ion was at approximately 0.2–0.5 mg/cm2/min and (2) exercise heat acclimation improved the sweat ion reabsorption ability and would increase the criteria 1. Seven healthy non-heat-acclimated male subjects received passive heat treatment both before and after 7 days of cycling in hot conditions (50% maximum oxygen uptake, 60 min/day, ambient temperature 32 °C, and 50% relative humidity). Subjects became partially heat-acclimated, as evidenced by the decreased end-exercise heart rate (p < 0.01), rate of perceived exhaustion (p < 0.01), and oesophageal temperature (p = 0.07), without alterations in whole body sweat loss, from the first to the last day of training. As hypothesized, we confirmed that the SR threshold for increasing GSC was near the predicted SR during passive heating before exercise heat acclimation, and increased significantly after training (0.19 ± 0.09–0.32 ± 0.10 mg/cm2/min, p < 0.05). The reproducibility of sweat ion reabsorption by the eccrine glands in the present study suggests that the relationship between GSC and SR can serve as a new index for assessing the maximum rate of sweat ion reabsorption of eccrine sweat glands in humans.

  9. Upregulation of renal BSC1 and TSC in prenatally programmed hypertension.

    PubMed

    Manning, Jennifer; Beutler, Kathleen; Knepper, Mark A; Vehaskari, V Matti

    2002-07-01

    Prenatal factors, especially intrauterine growth retardation, have been shown to correlate with the risk of essential hypertension in adult life, but the mechanisms are unknown. An experimental model of prenatal programming of hypertension in the rat, induced by a maternal low-protein diet during pregnancy, was employed to study the role of renal Na reabsorption in the pathogenesis. The abundance of the apical Na transporter type III Na/H exchanger (NHE3), bumetanide-sensitive Na-K-2Cl cotransporter (BSC1), thiazide-sensitive Na-Cl cotransporter (TSC), and the amiloride-sensitive epithelial Na channel (ENaC) was determined by semiquantitative immunoblotting in kidneys from the offspring at 4 wk of age, before hypertension became manifest. There were no significant differences between the experimental and control rats in the abundance of NHE3 or any of the ENaC subunits. In contrast, the quantity of BSC1 in the experimental group was increased to 302% of control (P < 0.001) and that of TSC to 157% of control (P < 0.05). Determination of specific mRNA levels by ELISA-linked RT-PCR revealed a significantly increased BSC1 mRNA at 1 day (P < 0.01), 4 wk (P < 0.01), and 8 wk (P < 0.001) of age, and a significantly increased TSC mRNA at 4 wk of age (P < 0.05) in the experimental group. The results suggest that prenatal programming of hypertension involves transcriptional upregulation of Na transport in thick ascending limb and distal convoluted tubule.

  10. Renal handling of sodium and water in the hypothyroid rat

    PubMed Central

    Michael, Ulrich F.; Barenberg, Robert L.; Chavez, Rafaelita; Vaamonde, Carlos A.; Papper, Solomon

    1972-01-01

    Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals. Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P]IN) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats. These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron. PMID:5024038

  11. Renal Autoregulation in Health and Disease

    PubMed Central

    Carlström, Mattias; Wilcox, Christopher S.; Arendshorst, William J.

    2015-01-01

    Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]i occurs predominantly by Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCC). Increased [Ca2+]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+ from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+ sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism

  12. Renal Cysts

    MedlinePlus

    ... 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 ...

  13. In vivo maturation of functional renal organoids formed from embryonic cell suspensions.

    PubMed

    Xinaris, Christodoulos; Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

    2012-11-01

    The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.

  14. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  15. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  16. In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions

    PubMed Central

    Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A.; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

    2012-01-01

    The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney. PMID:23085631

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

    PubMed Central

    Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

    2016-01-01

    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 effects of lesinurad on sUA were attenuated in moderate to severe renal impairment. PMID:27843295

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

    PubMed

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

    2013-09-05

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

  19. Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms.

    PubMed

    Van de Walle, J G; Donckerwolcke, R A; Greidanus, T B; Joles, J A; Koomans, H A

    1996-11-01

    We studied renal sodium handling during water diuresis in children in the early phase of relapse of minimal lesion nephrotic syndrome (MLNS). Findings were related to presence or absence of symptoms suggestive of hypovolaemia, and to neurohumoral factors, and were compared to results of similar studies in the same children in remission. Nine children (aged 7.8 +/- 3.1 years) presented with hypovolaemic symptoms, and 10 (7.4 +/- 4.3 years) without such symptoms. Both groups displayed severe proteinuria, hypoproteinaemia and oedema. Symptomatic patients showed tendency for a low glomerular filtration rate, and significantly impaired urine dilution, decreased fractional sodium and lithium excretions, and elevated diluting segment reabsorption [CH2O/(CH2O + CNa)] and sodium/potassium exchange [UK/(UK + UNa)]. In the non-symptomatic patients these parameters were normal. Plasma renin and aldosterone were significantly elevated in the symptomatic children, and strongly correlated with all parameters of tubule sodium reabsorption. Weaker associations were found for plasma noradrenaline and atrial natriuretic peptide. Vasopressin was also relatively high in the symptomatic group, but showed no association with impaired urine dilution. The diffusely stimulated tubular sodium reabsorption in the symptomatic children, in association with stimulated neurohumoral factors, indicates that secondary sodium retention contributes to oedema formation in at least a subset of children developing a nephrotic relapse. This may be limited to the early stage, and be more pronounced in some patients than in others. The tubular defect responsible for maintenance of oedema in stabilized MLNS remains unclear.

  20. Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

    PubMed

    Verouti, Sophia N; Boscardin, Emilie; Hummler, Edith; Frateschi, Simona

    2015-04-01

    The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Dopamine and angiotensin type 2 receptors cooperatively inhibit sodium transport in human renal proximal tubule cells.

    PubMed

    Gildea, John J; Wang, Xiaoli; Shah, Neema; Tran, Hanh; Spinosa, Michael; Van Sciver, Robert; Sasaki, Midori; Yatabe, Junichi; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2012-08-01

    Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells, sodium reabsorption is decreased by the dopamine D(1)-like receptors (D(1)R/D(5)R) and the angiotensin type 2 receptor (AT(2)R), whereas the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and, subsequently, hypertension. We show that D(1)R/D(5)R stimulation increased plasma membrane AT(2)R 4-fold via a D(1)R-mediated, cAMP-coupled, and protein phosphatase 2A-dependent specific signaling pathway. D(1)R/D(5)R stimulation also reduced the ability of angiotensin II to stimulate phospho-extracellular signal-regulated kinase, an effect that was partially reversed by an AT(2)R antagonist. Fenoldopam did not increase AT(2)R recruitment in renal proximal tubule cells with D(1)Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D(1)Rs and AT(2)Rs heterodimerized and cooperatively increased cAMP and cGMP production, protein phosphatase 2A activation, sodium-potassium-ATPase internalization, and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension.

  2. Mycelia glycoproteins from Cordyceps sobolifera ameliorate cyclosporine-induced renal tubule dysfunction in rats.

    PubMed

    Chyau, Charny-Cherng; Chen, Chin-Chu; Chen, Jun-Chang; Yang, Te-Cheng; Shu, Kuo-Hsiung; Cheng, Chi-Hung

    2014-05-14

    Cordyceps sorbolifera has been used in Traditional Chinese Medicine for improving the renal function. Cyclosporine A (CsA) is an important immunosuppressive agent in the prevention of renal allograft rejection, but long-term usage of CsA could lead to chronic nephrotoxicity and renal graft failure. The study was aimed to investigate whether the mycelia glycoproteins of Cordyceps sobolifera (CSP) exert prevention effects on CsA-induced nephrotoxicity. Sprague-Dawley (SD) rats were randomly assigned into four groups (n=6 per group): normal saline (control group), CSP group, CsA group, and CSP-CsA group (CsA combined treatment with CSP). Glomerular and tubular functions were assessed and histological studies were performed. CSP, prepared by hot water extraction, ethanol precipitation and membrane dialysis, was found to be composed of three glycoproteins with average molecular weights of 543, 31, and 6.3 kDa, respectively. CsA impaired urea clearance and creatinine clearance were significantly improved by concomitant administration of CSP. TUNEL histochemical stain revealed that CSP significantly decreased CsA-induced apoptosis in renal tubular cells. The reducing effect of caspase-3 activation by CSP was suggested through the over-expression of the anti-apoptosis protein Bcl-2 in renal tubule cells. In assessment of CSP protection of renal tubule function, we found that CSP restored CsA induced magnesium wasting by increasing the magnesium reabsorption channels TRMP6 and TRMP7. The results suggested that CSP had a significant suppressive activity on CsA-induced apoptosis and protective activity against nephron loss possibly via its restoring activity by increasing the magnesium reabsorption channels TRMP6 and TRMP7 on CsA induced magnesium wasting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation.

    PubMed

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

    1985-06-01

    Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.

  4. OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

    PubMed Central

    Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

    2015-01-01

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  5. Endothelin and endothelin receptors in the renal and cardiovascular systems.

    PubMed

    Vignon-Zellweger, Nicolas; Heiden, Susi; Miyauchi, Takashi; Emoto, Noriaki

    2012-10-15

    Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic and renal vascular resistance, salt and water renal reabsorption, and glomerular function. ET-1 is responsible for a variety of cellular events: contraction, proliferation, apoptosis, etc. These effects take place after the activation of the two endothelin receptors ET(A) and ET(B), which are present - among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial cells, glomerular and tubular cells of the kidney. The complex and numerous intracellular pathways, which can be contradictory in term of functional response depending on the receptor type, cell type and physiological situation, are described in this review. Many diseases share an enhanced ET-1 expression as part of the pathophysiology. However, the use of endothelin blockers is currently restricted to pulmonary arterial hypertension, and more recently to digital ulcer. The complexity of the endothelin system does not facilitate the translation of the molecular knowledge to clinical applications. Endothelin antagonists can prevent disease development but secondary undesirable effects limit their usage. Nevertheless, the increasing understanding of the effects of ET-1 on the cardiac and renal physiology maintains the endothelin system as a promising therapeutic target.

  6. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.

    PubMed

    Hall, John E; do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Hall, Michael E

    2015-03-13

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

  7. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    PubMed

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

  8. Mini-review: regulation of the renal NaCl cotransporter by hormones.

    PubMed

    Rojas-Vega, Lorena; Gamba, Gerardo

    2016-01-01

    The renal thiazide-sensitive NaCl cotransporter, NCC, is the major pathway for salt reabsorption in the distal convoluted tubule. The activity of this cotransporter is critical for regulation of several physiological variables such as blood pressure, serum potassium, acid base metabolism, and urinary calcium excretion. Therefore, it is not surprising that numerous hormone-signaling pathways regulate NCC activity to maintain homeostasis. In this review, we will provide an overview of the most recent evidence on NCC modulation by aldosterone, angiotensin II, vasopressin, glucocorticoids, insulin, norepinephrine, estradiol, progesterone, prolactin, and parathyroid hormone. Copyright © 2016 the American Physiological Society.

  9. An experimental renal acidification defect in patients with hereditary fructose intolerance

    PubMed Central

    Morris, R. Curtis

    1968-01-01

    In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO3-) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO3-) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO3- of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H+ secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO3- (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid. A reduced H+ secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO3- was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal. PMID:5658593

  10. Regulation of renal Na-(K)-Cl cotransporters by vasopressin.

    PubMed

    Bachmann, Sebastian; Mutig, Kerim

    2017-08-01

    Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption. Previous work has specified molecular pathways mediating the effects of V2R activation in TAL and DCT, and protein networks involved in intracellular trafficking and phosphoregulation of the two transporters have been identified. This review summarizes recent progress in understanding AVP signalling mechanisms that are responsible for the activation of NKCC2 and NCC. Implications in the pathophysiology of diseases such as nephrogenic diabetes insipidus, diabetes mellitus and salt-sensitive hypertension are discussed in this context.

  11. Renal transport of urate during diuretic-induced hypouricemia.

    PubMed

    Reese, O G; Steele, T H

    1976-06-01

    The effect of two weeks administration of a uricosuric diuretic (SKF-62698) on renal urate handling has been examined in 11 normal men. Plasma urate concentrations had declined by more than 60 per cent after two weeks. Urate excretion per unit of glomerular filtration rate and urate clearance (Curate) per unit of glomerular filtration rate were increased after the administration of SKF-62698. The importance of intact tubular secretion of urate in producing these changes was assessed by administering pyrazinamide, an agent that curtails urate secretion, to each participant. The decrements in urate excretion and clearance produced by pyrazinamide both increased significantly, whereas the residual urate excretion rates and clearances not suppressible by pyrazinamide were only minimally altered by SKF-62698 treatment. These results suggest that the excretion of secreted urate was enhanced by prolonged administration of SKF-62698, probably secondary to the inhibition of postsecretory urate reabsorption. In addition, because the nonsuppressible urate excretion did not decline despite a 63 per cent reduction in the plasma urate, it is likely that the reabsorption of filtered urate also was impaired by SKF-62698.

  12. Renal denervation for resistant hypertension.

    PubMed

    Almeida, Manuel de Sousa; Gonçalves, Pedro de Araújo; Oliveira, Eduardo Infante de; Carvalho, Henrique Cyrne de

    2015-02-01

    There is a marked contrast between the high prevalence of hypertension and the low rates of adequate control. A subset of patients with suboptimal blood pressure control have drug-resistant hypertension, in the pathophysiology of which chronic sympathetic hyperactivation is significantly involved. Sympathetic renal denervation has recently emerged as a device-based treatment for resistant hypertension. In this review, the pathophysiological mechanisms linking the sympathetic nervous system and cardiovascular disease are reviewed, focusing on resistant hypertension and the role of sympathetic renal denervation. An update on experimental and clinical results is provided, along with potential future indications for this device-based technique in other cardiovascular diseases.

  13. [Chronic renal insufficiency and secondary hyperparathyroidism in rats. Biochemical and histological evaluation].

    PubMed

    Virgós, M J; Menéndez-Rodríguez, P; Serrano, M; González-Carcedo, A; Braga, S; Cannata, J B

    1993-12-01

    Chronic renal failure (CRF) in rats (surgical nephrectomy, 5/6) as well as its derived bone lesions have been studied. Eighty-five male Wistar rats were used, to which chronic renal failure was induced in 1 or 2 surgical times, the parameters of renal function in basal conditions and at different times after surgery being determined. With the method used chronic renal failure is induced with values of creatinine clearance 2/3 times lower than the initial ones (p < 0.05), which stabilize at the 7th week. On the other hand the parathyroid hormone levels (PTH) in serum triple (from 125 +/- 49 to 395 +/- 191, p < 0.05), and a decrease in the tubular phosphate reabsorption is produced (p < 0.001). In bone histology an increase in resorption and bone formation is observed as well as paratrabecular fibrosis, all of which is compatible with the histological diagnosis of hyperparathyroidism. The model of surgical renal insufficiency with ablation of 5/6 of the renal mass, reduces renal function to 1/3 of the initial values after 7 weeks, this procedure having a 20% global mortality without differences being observed between the carrying out of nephrectomies in 1 or 2 surgical times. This degree of CRF was accompanied by secondary hyperparathyroidism both at the biochemical and histological levels, findings which are of great usefulness for future experimental studies.

  14. Regulation of renal hemodynamics after protein feeding: effects of proximal and distal diuretics.

    PubMed

    Woods, L L; Smith, B E; De Young, D R

    1993-02-01

    The purpose of these studies was to compare the effects of proximally and distally acting diuretics on the renal hemodynamic response to protein feeding to determine the importance of the proximal tubule in postprandial renal vasodilation. In chronically instrumented conscious dogs, a meat meal (10 g/kg raw beef) caused glomerular filtration rate (GFR) to increase from 63 +/- 5 to 87 +/- 10 ml/min and effective renal plasma flow (ERPF) to increase from 189 +/- 20 to 249 +/- 20 ml/min, while plasma alpha-amino nitrogen levels rose from 4.0 +/- 0.1 to 6.8 +/- 0.4 mg/dl. Administration of amiloride (0.2 mg/kg + 0.003 mg.kg-1.min-1) or potassium canrenoate (1.76 mg/kg + 1.76 mg.kg-1.h-1), diuretics that act in the distal tubule, had no effect on the renal hemodynamic responses to a meat meal. However, the normal renal hemodynamic responses to protein feeding were abolished during administration of a diuretic that acts in the proximal tubule, acetazolamide (20 mg/kg + 20 mg.kg-1.h-1), although plasma alpha-amino nitrogen levels increased after the meat meal in all experiments. These data suggest that normal proximal tubular sodium reabsorptive function is necessary for acute protein-stimulated renal vasodilation and are consistent with the hypothesis that a tubuloglomerular feedback mechanism may mediate postprandial renal vasodilation.

  15. A mathematical model of long-term renal sympathetic nerve activity inhibition during an increase in sodium intake

    PubMed Central

    Denizhan, Yagmur; Hester, Robert

    2013-01-01

    It is well known that renal nerves directly affect renal vascular resistance, tubular sodium reabsorption, and renin secretion. Inhibition of renal sympathetic nerve activity (RSNA) decreases renal vascular resistance, tubular sodium reabsorption, and renin secretion, leading to an increase in sodium excretion. Although several studies show that inhibition of RSNA promotes sodium excretion during an acute blood volume expansion, there is limited research relating to the importance of RSNA inhibition that contributes to sodium homeostasis during a long-term increase in sodium intake. Therefore, to dissect the underlying mechanisms of sodium excretion, a mathematical model of a cardiovascular system consisting of two kidneys, each with an independent RSNA, was developed. Simulations were performed to determine the responses of RSNA and sodium excretion to an increased sodium intake. In these simulations, RSNA in the left kidney was fixed at its normal steady-state value, while RSNA in the contralateral kidney was allowed to change normally in response to the increased sodium intake. The results demonstrate that the fixed-RSNA kidney excretes less sodium than the intact-RSNA collateral kidney. Because each kidney is exposed to the same arterial pressure and circulatory hormones, the impaired sodium excretion in the absence of RSNA inhibition supports the hypothesis that RSNA inhibition contributes to natriuresis in response to a long-term increase in sodium intake. PMID:24285363

  16. The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

    SciTech Connect

    Provoost, A.P.; Van Aken, M.

    1984-01-01

    In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. The accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.

  17. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  18. Evaluation of Pharmacokinetic Interactions Between Lesinurad, a New Selective Urate Reabsorption Inhibitor, and Commonly Used Drugs for Gout Treatment.

    PubMed

    Shen, Zancong; Tieu, Kathy; Wilson, David; Bucci, Gail; Gillen, Michael; Lee, Caroline; Kerr, Bradley

    2017-01-11

    Lesinurad is a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors (XOIs). Open-label pharmacokinetic studies were performed in volunteers or subjects with hyperuricemia (serum uric acid ≥ 8 mg/dL) to investigate interactions of lesinurad (with and without concurrent XOIs) with colchicine and 2 nonsteroidal anti-inflammatory drugs: naproxen and indomethacin. Colchicine studies included consecutive 7-day treatment periods of (1) allopurinol 300 mg, allopurinol 300 mg plus lesinurad 400 or 600 mg, and continued lesinurad 400 or 600 mg; or (2) febuxostat 40 or 80 mg, febuxostat 40 or 80 mg plus lesinurad 400 mg, and continued febuxostat 40 or 80 mg plus lesinurad 600 mg. Naproxen and indomethacin studies included lesinurad 400 mg on day 1, naproxen 250 mg twice daily or indomethacin 25 mg twice daily on days 2-6, and lesinurad 400 mg plus continued naproxen or indomethacin on days 7-13 and the morning of day 14. Lesinurad did not alter the pharmacokinetics of naproxen and modestly altered exposure to colchicine (AUC decrease of ≤ 25%) and indomethacin (AUC increase of ∼35%). Indomethacin did not alter the pharmacokinetics of lesinurad, whereas naproxen modestly decreased the Cmax of lesinurad by ∼27%.

  19. Quantification of re-absorption and re-emission processes to determine photon recycling efficiency in perovskite single crystals

    PubMed Central

    Fang, Yanjun; Wei, Haotong; Dong, Qingfeng; Huang, Jinsong

    2017-01-01

    Photon recycling, that is, iterative self-absorption and re-emission by the photoactive layer itself, has been speculated to contribute to the high open-circuit voltage in several types of high efficiency solar cells. For organic–inorganic halide perovskites that have yielded highly efficient photovoltaic devices, however, it remains unclear whether the photon recycling effect is significant enough to improve solar cell efficiency. Here we quantitatively evaluate the re-absorption and re-emission processes to determine photon recycling efficiency in hybrid perovskite with its single crystals by measuring the ratio of the re-emitted photons to the initially excited photons, which is realized by modulating their polarization to differentiate them. The photon recycling efficiencies are revealed to be less than 0.5% in CH3NH3PbI3 and CH3NH3PbBr3 single crystals under excitation intensity close to one sun, highlighting the intrinsically long carrier recombination lifetime instead of the photon-recycling-induced photon propagation as the origin of their long carrier diffusion length. PMID:28220791

  20. Analytical model of photon reabsorption in ZnO quantum dots with size and concentration dependent dual-color photoluminescence

    NASA Astrophysics Data System (ADS)

    Fan, Baolu; Guo, Xiaoxiao; Zhang, Yumeng; Fan, Jiyang

    2017-02-01

    We investigate the concentration and size dependent UV/green photoluminescence properties of the ZnO quantum dots (QDs) with sizes in the strong confinement regime. The luminescence characteristics of an ensemble of colloidal semiconductor QDs with quantum confinement effect depend sensitively on particle concentration but this has only been qualitatively understood. By taking ZnO QDs as an ideal prototype, we construct a material-independent theoretical model to study the photon reabsorption phenomenon. The theoretical result agrees well with the experiment. This model can be used to quantitatively study the concentration-dependent luminescence properties of any collection of QDs with considerable size dispersion. On the other hand, the origin of green emission in ZnO QDs remains debated. The comparative study of the size dependence of UV and green emissions in conjunction with the effective-mass approximation calculation suggests that the green emission in the ZnO QDs originates from the conduction band to the deep level transition.

  1. [Immunoglobulin filtration and reabsorption as possible factors in the pathogenesis of chronic glomerulonephritis. Clinical, immunomorphological and histoenzymological research].

    PubMed

    Nabokov, A V; Travkina, E S; Zel'tser, G L; Nevorotin, A I

    1992-01-01

    Kidney biopsy specimens obtained from a group of individuals with chronic glomerulonephritis (CGN) have been processed for light and electron microscopic immunolocalization of total immunoglobulins (Igs). In a few cases, acid phosphatase (ACPase), a lysosomal enzyme marker, was ultrastructurally visualized. In the glomeruli, horseradish peroxidase-stained Igs were revealed in capillary lumina, urinary spaces and in transit through occasional loci of the glomerular basal membranes while ACPase-containing lysosomes resided both within and outside the cells. In the proximal tubules, Igs were traced in the endocytic vesicles and vacuoles, the latter also being positive for ACPase. Statistically significant relationships have been revealed between the number of IGs-labeled proximal tubules and some clinical or pathomorphological stigmata of CGN, in particular, proteinuria and arterial hypertension levels, marked interstitial sclerosis, etc. The data obtained are discussed in regard to the mechanisms of increased macromolecular filtration and the different proteinuria selectivity levels as well as the development of interstitial sclerosis as a result of the elevated reabsorption and incomplete lysosomal degradation of Igs in CGN.

  2. Quantification of re-absorption and re-emission processes to determine photon recycling efficiency in perovskite single crystals

    NASA Astrophysics Data System (ADS)

    Fang, Yanjun; Wei, Haotong; Dong, Qingfeng; Huang, Jinsong

    2017-02-01

    Photon recycling, that is, iterative self-absorption and re-emission by the photoactive layer itself, has been speculated to contribute to the high open-circuit voltage in several types of high efficiency solar cells. For organic-inorganic halide perovskites that have yielded highly efficient photovoltaic devices, however, it remains unclear whether the photon recycling effect is significant enough to improve solar cell efficiency. Here we quantitatively evaluate the re-absorption and re-emission processes to determine photon recycling efficiency in hybrid perovskite with its single crystals by measuring the ratio of the re-emitted photons to the initially excited photons, which is realized by modulating their polarization to differentiate them. The photon recycling efficiencies are revealed to be less than 0.5% in CH3NH3PbI3 and CH3NH3PbBr3 single crystals under excitation intensity close to one sun, highlighting the intrinsically long carrier recombination lifetime instead of the photon-recycling-induced photon propagation as the origin of their long carrier diffusion length.

  3. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces

    PubMed Central

    Buishas, Joel; Gould, Ian G.; Linninger, Andreas A.

    2014-01-01

    Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 µL per mOsm in the ventricle and by 0.835 µL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema. PMID:25358881

  4. [Comparison of reabsorption of osmotically free water in the bud and energy of interaction of vasotocin analogs with a V2-receptor].

    PubMed

    Kutina, A V; Karavashkina, T A; Shakhmatova, E I; Gao, Ts; Mordvintsev, D Iu; Kuz'min, D A; Tsetlin, V I; Natochin, Iu V

    2011-01-01

    The calculated values of the binding energy of nonapeptides with receptors in docking with their influence on reabsorption of osmotically free water in a rat bud in vivo were compared. Vasotocin and some its analogs were intramuscularly introduced to non-narcotized rat females of the Wistar line in doses from 0.1 pmol to 0.5 nmol/kg of body weight against the background of peroral water load (50 ml/kg of body weight). A significant correlation between the calculated interaction energy of peptides with V2-receptors and an increase of reabsorption of osmotically free water in the rat bud stimulated by injection of nonapeptides was found. The results evidence that alterations in rat bud in vivo caused by analogs of vasotocin and their interactions with V2-receptors can be accurately simulated.

  5. Prediction of bone mass in renal hyperparathyroidism by newly developed bone metabolic markers: evaluation of serum levels of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen.

    PubMed

    Katagiri, M; Fukunaga, M; Ohtawa, T; Harada, T

    1996-09-01

    Serum levels of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the carboxy-terminal propeptide of type I procollagen (PICP) were measured in 95 patients with renal hyperparathyroidism who had undergone a total parathyroidectomy and autotransplantation of a small portion of the resected gland. The results were compared with the serum levels of other bone metabolic markers and bone mineral densities in the distal radius (R-BMD) and lumbar vertebrae (L-BMD), which were measured by dual energy x-ray absorptiometry and converted to the percentage of the mean value of sex- and age-matched healthy controls. The preoperative mean values of ICTP and PICP were 142.4 ng/ml and 187.8 ng/ml, respectively. Although the serum levels of PICP levels exceeded the normal range in 42.1% of the patients, those of ICTP exceeded it in all of them. The serum levels of ICTP correlated positively not only with those of tartrate-resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP), and osteocalcin but also negatively with the values of %R-BMD and %L-BMD and seemed to manifest specifically the disturbance of bone metabolism. On the other hand, the serum levels of PICP correlated with those of ALP and TRACP but not with values of %BMDs. After surgery, the serum levels of ICTP decreased gradually, but those of PICP increased immediately up to peak values at 7 days and then decreased gradually after 14 days, reaching the normal range at 3 months. These changes in the bone metabolic markers seemed to reflect the change in bone metabolism that was converting from bone resorption to bone formation. The percent change in the PICP/ICTP ratio at 7 days correlated significantly with the percent change in R-BMD at 12 months, and it was suggested that postoperative bone gain might be predicted using a combination of postoperative changes in PICP and ICTP.

  6. Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir

    PubMed Central

    Yang, Xi; Ma, Zhiyuan; Zhou, Sisi; Weng, Yayun; Lei, Hongmei; Zeng, Su

    2016-01-01

    Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 μM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption. PMID:27503646

  7. Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation.

    PubMed

    Ledeganck, Kristien J; De Winter, Benedicte Y; Van den Driessche, Annelies; Jürgens, Angelika; Bosmans, Jean-Louis; Couttenye, Marie M; Verpooten, Gert A

    2014-05-01

    Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg(2+) leak. In animal studies a role for the Mg(2+) channel TRPM6 localized in the distal convoluted tubule and stimulated by epidermal growth factor (EGF) is suggested. We hypothesize that CsA-induced hypomagnesaemia is due to a renal magnesium leak, also in patients, resulting from a downregulation of the renal EGF production, thereby inhibiting the activation of TRPM6. Renal transplant patients treated with CsA (n = 55) and 35 chronic kidney disease (CKD) patients were included. At three time points, with an interval of at least 1 month, blood and urine samples were taken to determine creatinine, Mg(2+), sodium and EGF. Serum Mg(2+) was significantly lower in the CsA group versus the CKD group with significantly more CsA-treated patients developing hypomagnesaemia. Although the fractional excretion (FE) Mg(2+) did not differ significantly between the two groups, subanalysis of the patients with hypomagnesaemia showed a significantly higher FE Mg(2+) in CsA-treated patients compared with CKD patients (P = 0.05). The urinary EGF excretion was significantly decreased in the CsA group and was a predictor of the FE Mg(2+) in the two groups. Serum sodium was significantly decreased in the CsA group simultaneously with an increased FE Na(+). In CsA-treated patients, the association of a low urinary EGF excretion and a decreased renal Mg(2+) reabsorption is in accordance with in vitro and animal studies. In the whole study population, log urinary EGF excretion is an independent predictor of the FE Mg(2+), supporting the role of EGF in magnesium reabsorption.

  8. Renal Denervation

    PubMed Central

    Persu, Alexandre; Renkin, Jean; Thijs, Lutgarde; Staessen, Jan A.

    2013-01-01

    The term “ultima ratio” has multiple, though related, meanings. The motto “ultima ratio regum,” cast on the cannons of the French army of King Louis XIV, meant that war is the last argument of kings, that is, the one to be used after all diplomatic arguments have failed. Along similar lines, we propose that, given the current evidence, renal denervation should be used as a last resort, after state-of-the-art drug treatment optimized at expert centers failed to control blood pressure. PMID:22851728

  9. Renal disease in pregnancy.

    PubMed

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  10. [Acute renal insufficiency and fat embolism].

    PubMed

    Ohresser, P; Sainty, J M; Belnet, M; Cano, N

    1975-10-01

    The authors report ten cases of renal insufficiency observed among a series of 43 cases of fat embolism. It is a matter of eraly oligoanuria (starting beween the 2nd and the 4th day). Its severity depends on the lesions involved : prolonged cardio-vascular collapse - cranio-encephalic lesion. The renal insufficiency does not seem typical of fat embolism. It must be essentially linked to a cardio-vascular collapse and/or to a disseminated intra-vascular coagulation.

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

    SciTech Connect

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

    1986-01-01

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

  12. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue.

    PubMed Central

    Hammond, P. J.; Wade, A. F.; Gwilliam, M. E.; Peters, A. M.; Myers, M. J.; Gilbey, S. G.; Bloom, S. R.; Calam, J.

    1993-01-01

    The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue. Eight patients being scanned with the 111In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance. Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate. This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments. Images Figure 1 PMID:8099808

  13. Salt-dependent inhibition of ENaC-mediated sodium reabsorption in the aldosterone-sensitive distal nephron by bradykinin

    PubMed Central

    Mamenko, Mykola; Zaika, Oleg; Doris, Peter A.; Pochynyuk, Oleh

    2012-01-01

    We have recently documented that Bradykinin (BK) directly inhibits activity of the Epithelial Na+ Channel (ENaC) via B2R-Gq/11-PLC pathway. In this study, we took advantage of mice genetically engineered to lack bradykinin receptors (B1R,B2R-/-) to probe a physiological role of BK cascade in regulation of ENaC in native tissue, aldosterone-sensitive distal nephron (ASDN). Under normal sodium intake (0.32%Na+), ENaC open probability (Po) was modestly elevated in B1R,B2R-/- mice compared to WT mice. This difference is augmented during elevated Na+ intake (2%Na+) and negated during Na+ restriction (<0.01%Na+). Saturation of systemic mineralocorticoid status with deoxycorticosterone acetate (DOCA) similarly increased ENaC activity in both mouse strains suggesting that the effect of BK on ENaC is independent of aldosterone. It is accepted that angiotensin converting enzyme (ACE) represents the major pathway of BK degradation. Systemic inhibition of ACE with captopril (30 mg/kgBW for 7 days) significantly decreases ENaC activity and Po in WT mice but this effect is diminished in B1R,B2R-/- mice. At the cellular level, acute captopril (100 μM) treatment sensitized BK signaling cascade and greatly potentiated the inhibitory effect of 100 nM BK on ENaC. We concluded that BK cascade has its own specific role in blunting ENaC activity particularly under conditions of elevated sodium intake. Augmentation of BK signaling in the ASDN inhibits ENaC-mediated Na+-reabsorption contributing to the natriuretic and antihypertensive effects of ACE inhibition. PMID:23033373

  14. Dietary Fructose Enhances the Ability of Low Concentrations of Angiotensin II to Stimulate Proximal Tubule Na+ Reabsorption

    PubMed Central

    Gonzalez-Vicente, Agustin; Cabral, Pablo D.; Hong, Nancy J.; Asirwatham, Jessica; Yang, Nianxin; Berthiaume, Jessica M.; Dominici, Fernando P.; Garvin, Jeffrey L.

    2017-01-01

    Fructose-enriched diets cause salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the water and salt filtered through the glomerulus. Angiotensin II (Ang II) regulates this process. Normally, dietary salt reduces Ang II allowing the kidney to excrete more salt, thereby preventing hypertension. We hypothesized that fructose-enriched diets enhance the ability of low concentrations of Ang II to stimulate PT transport. We measured the effects of a low concentration of Ang II (10−12 mol/L) on transport-related oxygen consumption (QO2), and Na/K-ATPase and Na/H-exchange (NHE) activities and expression in PTs from rats consuming tap water (Control) or 20% fructose (FRUC). In FRUC-treated PTs, Ang II increased QO2 by 14.9 ± 1.3 nmol/mg/min (p < 0.01) but had no effect in Controls. FRUC elevated NHE3 expression by 19 ± 3% (p < 0.004) but not Na/K-ATPase expression. Ang II stimulated NHE activity in FRUC PT (Δ + 0.7 ± 0.1 Arbitrary Fluorescent units (AFU)/s, p < 0.01) but not in Controls. Na/K-ATPase activity was not affected. The PKC inhibitor Gö6976 blocked the ability of FRUC to augment the actions of Ang II. FRUC did not alter the inhibitory effect of dopamine on NHE activity. We conclude that dietary fructose increases the ability of low concentrations of Ang II to stimulate PT Na reabsorption via effects on NHE. PMID:28813008

  15. Temporal changes in floral nectar production, reabsorption, and composition associated with dichogamy in annual caraway (Carum carvi; Apiaceae).

    PubMed

    Langenberger, Michael W; Davis, Arthur R

    2002-10-01

    The dynamics of nectar production were studied in perfect florets of two varieties (Karzo, Moran) of annual caraway (Carum carvi L., Apiaceae). Florets were protandrous and strongly dichogamous, lasting 7-15 d but producing nectar from the stylopodia for 4-12 d, in an interrupted fashion. Nectar secretion began during a floret's phase of stamen elongation and anther dehiscence. After reabsorption of uncollected nectar, at which point nectary surfaces were completely dry, the two styles elongated and a second bout of secretion commenced during the female phase, up to 5 d later, when a floret became receptive to pollination. During the male and female phases, respectively, 0.392 ± 0.064 μL and 1.083 ± 0.261 μL of nectar of similar solute concentration (844 mg/mL) was produced per ten florets. On a daily basis, florets yielded 1.5-fold more nectar in the female than during the male phase. First-time nectar removal throughout the female phase did not match the sum of nectar quantities from male and female phases combined, suggesting that under natural conditions, any uncollected male-phase nectar, once reabsorbed, is not made available to visitors of the same florets when in the female phase. Nectar-sugar composition differed between bouts of secretion; it was hexose-rich (59.6% fructose, 26.9% glucose, 13.6% sucrose) initially, but hexose-dominant (70.2, 26.8, 3.1) during the female phase. A 5.7-fold difference in mean nectar production per floret occurred among plants.

  16. Dietary Fructose Enhances the Ability of Low Concentrations of Angiotensin II to Stimulate Proximal Tubule Na⁺ Reabsorption.

    PubMed

    Gonzalez-Vicente, Agustin; Cabral, Pablo D; Hong, Nancy J; Asirwatham, Jessica; Yang, Nianxin; Berthiaume, Jessica M; Dominici, Fernando P; Garvin, Jeffrey L

    2017-08-16

    Fructose-enriched diets cause salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the water and salt filtered through the glomerulus. Angiotensin II (Ang II) regulates this process. Normally, dietary salt reduces Ang II allowing the kidney to excrete more salt, thereby preventing hypertension. We hypothesized that fructose-enriched diets enhance the ability of low concentrations of Ang II to stimulate PT transport. We measured the effects of a low concentration of Ang II (10(-12) mol/L) on transport-related oxygen consumption (QO₂), and Na/K-ATPase and Na/H-exchange (NHE) activities and expression in PTs from rats consuming tap water (Control) or 20% fructose (FRUC). In FRUC-treated PTs, Ang II increased QO₂ by 14.9 ± 1.3 nmol/mg/min (p < 0.01) but had no effect in Controls. FRUC elevated NHE3 expression by 19 ± 3% (p < 0.004) but not Na/K-ATPase expression. Ang II stimulated NHE activity in FRUC PT (Δ + 0.7 ± 0.1 Arbitrary Fluorescent units (AFU)/s, p < 0.01) but not in Controls. Na/K-ATPase activity was not affected. The PKC inhibitor Gö6976 blocked the ability of FRUC to augment the actions of Ang II. FRUC did not alter the inhibitory effect of dopamine on NHE activity. We conclude that dietary fructose increases the ability of low concentrations of Ang II to stimulate PT Na reabsorption via effects on NHE.

  17. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects.

    PubMed

    Shen, Zancong; Gillen, Michael; Miner, Jeffrey N; Bucci, Gail; Wilson, David M; Hall, Jesse W

    2017-01-01

    Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males. This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10-12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests, vital signs, and electrocardiograms (ECGs). A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose-proportional manner; Cmax occurred at 0.5-0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported. Single and multiple doses of verinurad were well tolerated, absorption was rapid, and exposure was dose proportional. Verinurad increased urinary uric acid elimination and resulted in sustained reductions in serum urate. These data support further clinical evaluation of once-daily verinurad as a treatment for

  18. Comparative Analysis of Novel Noninvasive Renal Biomarkers and Metabonomic Changes in a Rat Model of Gentamicin Nephrotoxicity

    PubMed Central

    Sieber, Max; Hoffmann, Dana; Adler, Melanie; Vaidya, Vishal S.; Clement, Matthew; Bonventre, Joseph V.; Zidek, Nadine; Rached, Eva; Amberg, Alexander; Callanan, John J.; Dekant, Wolfgang; Mally, Angela

    2009-01-01

    Although early detection of toxicant induced kidney injury during drug development and chemical safety testing is still limited by the lack of sensitive and reliable biomarkers of nephrotoxicity, omics technologies have brought enormous opportunities for improved detection of toxicity and biomarker discovery. Thus, transcription profiling has led to the identification of several candidate kidney biomarkers such as kidney injury molecule (Kim-1), clusterin, lipocalin-2, and tissue inhibitor of metalloproteinase 1 (Timp-1), and metabonomic analysis of urine is increasingly used to indicate biochemical perturbations due to renal toxicity. This study was designed to assess the value of a combined 1H-NMR and gas chromatography–mass spectrometry (GC-MS) metabonomics approach and a set of novel urinary protein markers for early detection of nephrotoxicity following treatment of male Wistar rats with gentamicin (60 and 120 mg/kg bw, sc) for 7 days. Time- and dose-dependent separation of gentamicin-treated animals from controls was observed by principal component analysis of 1H-NMR and GC-MS data. The major metabolic alterations responsible for group separation were linked to the gut microflora, thus related to the pharmacology of the drug, and increased glucose in urine of gentamicin-treated animals, consistent with damage to the S1 and S2 proximal tubules, the primary sites for glucose reabsorption. Altered excretion of urinary protein biomarkers Kim-1 and lipocalin-2, but not Timp-1 and clusterin, was detected before marked changes in clinical chemistry parameters were evident. The early increase in urine, which correlated with enhanced gene and protein expression at the site of injury, provides further support for lipocalin-2 and Kim-1 as sensitive, noninvasive biomarkers of nephrotoxicity. PMID:19349640

  19. SLC5 Sodium-Anion Cotransporters and Renal Urate Transport

    NASA Astrophysics Data System (ADS)

    Mount, David B.; Kwon, Charles Y.; Plata, Consuelo; Romero, Michael F.; Zandi-Nejad, Kambiz

    2007-04-01

    Renal urate transport plays a key role in determining the concentration of circulating uric acid. The reabsorption of filtered urate by the renal proximal tubule appears to require apical sodium-dependent anion transport and the apical URAT1 urate-anion exchanger, in that sodium-dependent transport of lactate, ketoacids, nicotinate, and pyrazinoate (PZA) increases the intracellular concentration of substrates for the subsequent exchange with luminal urate. We have identified SLC5A8 and SLC5A12 as candidates for the sodium-anion cotransporter that collaborates with URAT1. Both transporters function as sodium-dependent nicotinate/monocarboxylate/PZA transporters. Localization studies reveal serial co-expression of these transporters with URAT1, with Slc5a12 in the early proximal tubule and Slc5a8 in S2 and S3 segments. Renal urate excretion is conceivably affected by changes in the activity of SLC5A8, SLC5A12, and/or URAT1, with implications for the pathogenesis of hyperuricemia, nephrolithiasis, and related disorders.

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

    PubMed

    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.

  1. SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

    PubMed

    Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

    2016-08-01

    At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc.

  2. [A case of sarcoidosis with hypercalcemia, urolithiasis, nephrocalcinosis and renal insufficiency].

    PubMed

    Nunohiro, T; Aoi, W; Kadota, J; Ueda, Y; Takahara, O; Yura, M

    1992-08-01

    A sixty nine-year-old woman was admitted to the hospital because of further examination of hypercalcemia. On July 1990, she complained of general fatigue and loss of appetite. She was pointed out to have hypercalcemia (15.1mg/dl), urolithiasis, and renal insufficiency. CT films of the chest showed swelling of the mediastinal lymphnodes and CT of the abdomen nephrocalcinosis. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in the mediastinum. Levels of the parathyroid hormone was normal. Levels of the serum calcium (13.7mg/dl), angiotensin converting enzyme (30.4IU/L) and 1.25 (OH)2D (87PG/ml) were elevated. Giant cells were found in the biopsy specimen of the lung. A significant relationship between the serum calcium and creatinine were observed (r = 0.76, p < 0.02). Proximal fractional reabsorption of sodium showed to be suppressed (47.7%), and distal fractional reabsorption of sodium showed to be normal (88.4%). From these findings hypercalcemia and urolithiasis was suggested to result from sarcoidosis. The hypercalcemia and renal insufficiency improved with corticosteroid therapy.

  3. Dopamine and Angiotensin Type 2 Receptors Cooperatively Inhibit Sodium Transport in Human Renal Proximal Tubule Cells

    PubMed Central

    Gildea, John J.; Wang, Xiaoli; Shah, Neema; Tran, Hanh; Spinosa, Michael; Van Sciver, Robert; Sasaki, Midori; Yatabe, Junichi; Carey, Robert M.; Jose, Pedro A.; Felder, Robin A.

    2012-01-01

    Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells (RPTCs), sodium reabsorption is decreased by the dopamine D1-like receptors (D1R/D5R) and the angiotensin type 2 receptor (AT2R), while the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and subsequently hypertension. We show that D1R/D5R stimulation increased plasma membrane AT2R 4-fold via a D1R-mediated, cAMP-coupled, and PP2A-dependent specific signaling pathway. D1R/D5R stimulation also reduced the ability of angiotensin II to stimulate phospho-ERK, an effect that was partially reversed by an AT2R antagonist. Fenoldopam did not increase AT2R recruitment in RPTCs with D1Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D1Rs and AT2Rs heterodimerized and cooperatively increased cAMP and cGMP production, PP2A activation, sodium-potassium-ATPase internalization and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension. PMID:22710646

  4. Kappa-opioid-receptor agonists modulate the renal excretion of water and electrolytes in anaesthetized rats.

    PubMed Central

    Ashton, N.; Balment, R. J.; Blackburn, T. P.

    1990-01-01

    1. Subcutaneous injection of the kappa-opioid agonists U50,488 (10 mg kg-1) and tifluadom (3.5 mg kg-1) into Inactin-anaesthetized, saline-infused rats was associated with a diuresis, antinatriuresis and antikaliuresis which lasted for up to 2 h. A high (5 mg kg-1), but not low (0.1 mg kg-1), dose of naloxone blocked the renal effects of U50,488. 2. U50,488 administration in anaesthetized, vasopressin-deficient Brattleboro DI rats was associated with an attenuated diuresis, though the antinatriuretic response remained intact. 3. The diuretic action of U50,488 was associated with an increase in glomerular filtration rate while fractional fluid reabsorption remained steady. In contrast, fractional sodium and potassium reabsorption were increased. 4. These data suggest that kappa-opioid agonists alter renal handling of both water and electrolytes. This appears to be mediated by two separate mechanisms: increased fluid loss largely reflects altered glomerular events while the fall in electrolyte excretion results from altered tubular handling. PMID:2158834

  5. The effect of an intravenous infusion of hypertonic saline on renal mechanisms and on electrolyte changes in sheep

    PubMed Central

    Potter, B. J.

    1966-01-01

    1. The ability of the sheep to tolerate excess sodium chloride has been investigated by subjecting sheep to an intravenous infusion of a 10% solution of sodium chloride. 2. Inulin and diodrast clearances failed to show any consistent changes in glomerular filtration rate but the effective renal plasma flow was slightly more. Plasma levels of sodium and chloride increased by 20-25% and potassium decreased by 30%. Urinary levels for sodium and chloride showed a corresponding increase and potassium excretion was reduced. 3. The rates of re-absorption of sodium and chloride from the renal tubules were found to be proportional to their rates of filtration at the glomerulus, but this ratio was reduced after the hypertonic saline infusion. No such correlation could be established for potassium. 4. Osmolar clearances indicated that continued re-absorption of osmotically free water from the kidney tubular fluid occurred during and after the hypertonic saline. Excretion of urine, hyperosmotic to plasma, was thus maintained and water conservation supported. 5. Possible renal mechanisms associated with these effects are discussed. PMID:5963734

  6. Effect of prostaglandin E1 on certain renal actions of parathyroid hormone

    PubMed Central

    Beck, Nama P.; DeRubertis, Frederick R.; Michelis, Michael F.; Fusco, Robert D.; Field, James B.; Davis, Bernard B.

    1972-01-01

    Parathyroid hormone increased basal adenyl cyclase activity and that increase was inhibited by prostaglandin E1 (PGE1). Tissue cyclic 3′,5′-adenosine monophosphate (cyclic AMP) concentrations were increased by parathyroid hormone and that increase was likewise inhibited by PGE1. Both parathyroid hormone and dibutyryl cyclic AMP increased 32P incorporation into renal cortical phospholipids. PGE1 diminished the effect of parathyroid hormone but not dibutyryl cyclic AMP to influence that parameter. PGE1 likewise modulated the effect of parathyroid hormone but not dibutyryl cyclic AMP to decrease fractional phosphate reabsorption by the renal tubule. It is suggested that PGE1 inhibits the effect of parathyroid hormone by decreasing its effect on adenyl cyclase. Such interaction may be important in modulating the intracellular action of parathyroid hormone on kidney cortex. PMID:4344730

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Impairment of renal sodium excretion in tropical residents - phenomenological analysis

    NASA Astrophysics Data System (ADS)

    Arthur, S. K.; Aryee, P. A.; Amuasi, J.; Hesse, I. F. A.; Affram, R. K.

    There is evidence of impaired renal sodium excretion in salt-sensitive African Blacks. A decreased rate of renal sodium chloride (NaCl) excretion, low plasma renin activity and a tendency to elevated blood pressure are the hallmarks of salt sensitivity. Recent evidence indicates that increased proximal and distal tubular fluid reabsorption in some tropical residents may explain the impaired sodium excretion in these people. In this study of a cohort population, we speculated that subjects selected from that population might be salt-sensitive. We therefore measured the sodium balance in 10 normotensive male subjects over 10 consecutive days, after they had ingested a normal or a high amount of sodium, as NaCl (salt) in their diet. We quantified their renal sodium excretion rate by phenomenological analysis of their sodium balance data. We also measured plasma renin activity for 7 consecutive days in a separate group of 6 male and 4 female subjects in order to assess the state of their renin/angiotensin system. We selected all our subjects from a cohort population of 269 subjects randomly selected from a community known to have a high prevalence of primary hypertension. Our data on two separate groups of subjects from the same cohort population revealed delayed renal sodium excretion with t1/2 of about 5 days, compared to published data for normal individuals with t1/2 of less than 24 h. Also, plasma renin activity levels were low. Hence, our subjects are salt-sensitive. Quantification of their renal impairment is important for various reasons: it heightens one's appreciation of the problem of salt retention in African Blacks who are salt-sensitive and it also underlines the importance of the need for further research into the benefits of dietary salt restriction for reducing cardiovascular mortality in African populations, as has been done in some Western countries.

  9. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  10. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  11. Molecular mechanisms of renal aging.

    PubMed

    Schmitt, Roland; Melk, Anette

    2017-09-01

    Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Role of NH3 and NH4+ transporters in renal acid-base transport

    PubMed Central

    Verlander, Jill W.

    2011-01-01

    Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ “trapping” is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl− cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review. PMID:21048022

  13. Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

    PubMed Central

    Fu, Yiling; Vallon, Volker

    2014-01-01

    An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

  14. Chloride transporters and receptor-mediated endocytosis in the renal proximal tubule

    PubMed Central

    Devuyst, Olivier; Luciani, Alessandro

    2015-01-01

    Abstract The epithelial cells lining the proximal tubules of the kidney reabsorb a large amount of filtered ions and solutes owing to receptor-mediated endocytosis and polarized transport systems that reflect final cell differentiation. Dedifferentiation of proximal tubule cells and dysfunction of receptor-mediated endocytosis characterize Dent’s disease, a rare disorder caused by inactivating mutations in the CLCN5 gene that encodes the endosomal chloride–proton exchanger, ClC-5. The disease is characterized by a massive urinary loss of solutes (renal Fanconi syndrome), with severe metabolic complications and progressive renal failure. Investigations of mutations affecting the gating of ClC-5 revealed that the proximal tubule dysfunction may occur despite normal endosomal acidification. In addition to defective endocytosis, proximal tubule cells lacking ClC-5 show a trafficking defect in apical receptors and transporters, as well as lysosomal dysfunction and typical features of dedifferentiation, proliferation and oxidative stress. A similar but milder defect is observed in mouse models with defective CFTR, a chloride channel that is also expressed in the endosomes of proximal tubule cells. These data suggest a major role for endosomal chloride transport in the maintenance of epithelial differentiation and reabsorption capacity of the renal proximal tubule. Key points The reabsorptive activity of renal proximal tubule cells is mediated by receptor-mediated endocytosis and polarized transport systems that reflect final cell differentiation. Loss-of-function mutations of the endosomal chloride–proton exchanger ClC-5 (Dent’s disease) cause a major trafficking defect in proximal tubule cells, associated with lysosomal dysfunction, oxidative stress and dedifferentiation/proliferation. A similar but milder defect is associated with mutations in CFTR (cystic fibrosis transmembrane conductance regulator). Vesicular chloride transport appears to be important for

  15. Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization.

    PubMed

    Khurana, Manoj; Vaidyanathan, Jayabharathi; Marathe, Anshu; Mehrotra, Nitin; Sahajwalla, Chandrahas G; Zineh, Issam; Jain, Lokesh

    2015-06-01

    Canagliflozin (INVOKANA™) is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby, reducing reabsorption of filtered glucose and increasing urinary glucose excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the interplay between renal function, efficacy (HbA1c reduction), and safety (renal adverse reactions). The focus of this article is to highlight the FDA's quantitative clinical pharmacology analyses that were conducted to support the regulatory decision on dosing in patients with renal impairment (RI). The metrics for assessment of efficacy for T2DM drugs is standard; however, there is no standard method for evaluation of renal effects for diabetes drugs. Therefore, several analyses were conducted to assess the impact of canagliflozin on renal function (as measured by eGFR) based on available data. These analyses provided support for approval of canagliflozin in T2DM patients with baseline eGFR ≥ 45 mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The availability of a relatively rich safety dataset (ie, frequent and early measurements of laboratory markers) in the canagliflozin clinical development program enabled adequate assessment of benefit-risk balance in various patient subgroups based on renal function.

  16. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects

    PubMed Central

    Shen, Zancong; Gillen, Michael; Miner, Jeffrey N; Bucci, Gail; Wilson, David M; Hall, Jesse W

    2017-01-01

    Purpose Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males. Subjects and methods This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10–12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests, vital signs, and electrocardiograms (ECGs). Results A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) increased in a dose-proportional manner; Cmax occurred at 0.5–0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%−53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported. Conclusion Single and multiple doses of verinurad were well tolerated, absorption was rapid, and exposure was dose proportional. Verinurad increased urinary uric acid elimination and resulted in sustained reductions in serum urate. These data support further

  17. The endocannabinoid system in renal cells: regulation of Na+ transport by CB1 receptors through distinct cell signalling pathways

    PubMed Central

    Sampaio, L S; Taveira Da Silva, R; Lima, D; Sampaio, C L C; Iannotti, F A; Mazzarella, E; Di Marzo, V; Vieyra, A; Reis, R A M; Einicker-Lamas, M

    2015-01-01

    Background and Purpose The function of the endocannabinoid system (ECS) in renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the re-absorption of 70–80% of the filtrate. We studied the effect of compounds modulating the activity of cannabinoid (CB) receptors on the active re-absorption of Na+ in LLC-PK1 cells. Experimental Approach Changes in Na+/K+-ATPase activity were assessed after treatment with WIN55,212-2 (WIN), a non-selective lipid agonist, and haemopressin (HP), an inverse peptide agonist at CB1 receptors. Pharmacological tools were used to investigate the signalling pathways involved in the modulation of Na+ transport. Key Results In addition to CB1 and CB2 receptors and TRPV1 channels, the mRNAs encoding for enzymes of the ECS were also expressed in LLC-PK1. WIN (10−7 M) and HP (10−6 M) altered Na+ re-absorption in LLC-PK1 in a dual manner. They both acutely (after 1 min) increased Na+/K+-ATPase activity in a TRPV1 antagonist-sensitive way. WIN's stimulating effect persisted for 30 min, and this effect was partially blocked by a CB1 antagonist or a PKC inhibitor. In contrast, HP inhibited Na+/K+-ATPase after 30 min incubation, and this effect was attenuated by a CB1 antagonist or a PKA inhibitor. Conclusion and Implications The ECS is expressed in LLC-PK1 cells. Both CB1 receptors and TRPV1 channels regulate Na+/K+-ATPase activity in these cells, and are modulated by lipid and peptide CB1 receptor ligands, which act via different signalling pathways. PMID:25537261

  18. Metabolic Syndrome and Renal Injury

    PubMed Central

    Sheen, Yi-Jing; Sheu, Wayne Huey-Herng

    2011-01-01

    Both metabolic syndrome (MetS) and chronic kidney disease (CKD) are major global health issues. Current clinical markers used to reflect renal injury include albuminuria and estimated glomerular filtration rate (eGFR). Given the same eGFR level, urine albumin might be a better risk marker to predict progression of CKD and future development of cardiovascular diseases (CVDs). Serum Cystatin C is emerging as a new biomarker for early detection of renal injury associated with MetS and cardiovascular risk. In addition to each component, MetS per se influences the incidence and prognosis of renal injury and the odds ratios increased with the increase in the number of metabolic abnormalities. Hyperinsulinemia, activation of rennin-angiotensin-aldosterone system, increase of oxidative stress, and inflammatory cytokines are proposed to be the plausible biological link between MetS and CKD. Weight control, stick control of blood pressure, glucose, and lipids disorders may lead to lessening renal injury and even the subsequent CVD. PMID:21461396

  19. Ochratoxin A induced premature senescence in human renal proximal tubular cells.

    PubMed

    Yang, Xuan; Liu, Sheng; Huang, Chuchu; Wang, Haomiao; Luo, Yunbo; Xu, Wentao; Huang, Kunlun

    2017-05-01

    Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP). Cell cycle arrest and cell shape alternations also confirmed senescence. In addition, telomere analysis by RT-qPCR allowed us to classify OTA-induced senescence as a premature senescence. Western blot assays showed that the p53-p21 and the p16-pRB pathways and the ezrin-associated cell spreading changes were activated during the OTA-induced senescence of HKC. In conclusion, our results demonstrate that OTA promotes the senescence of HKC through the p53-p21 and p16-pRB pathways. The understanding of the mechanisms of OTA-induced senescence is critical in determining the role of OTA in cytotoxicity and its potential carcinogenicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function.

    PubMed

    Huang, Jiaguo; Weinfurter, Stefanie; Pinto, Pedro Caetano; Pretze, Marc; Kränzlin, Bettina; Pill, Johannes; Federica, Rodeghiero; Perciaccante, Rossana; Ciana, Leopoldo Della; Masereeuw, Rosalinde; Gretz, Norbert

    2016-10-19

    Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal clearance of designed drugs. It displays favorable fluorescent properties, high hydrophilicity, low plasma protein binding, and high stability in porcine liver esterase as well as in plasma and nontoxicity. More importantly, FITC-HPβCD can be efficiently and rapidly filtered by glomerulus and completely excreted into urine without proximal tubular reabsorption or secretion in rat models. Additionally, the marker was well-tolerated, with nearly 100% urinary recovery of the given doses, and no metabolism were found. Relying on this novel kidney function marker and transcutaneous devices, we demonstrate a rapid, robust, and convenient approach for real-time assessing renal function without the need of time-consuming blood and urine sample preparation. Our work provides a promising tool for noninvasive real-time monitoring of renal function in vivo.

  1. Accurate determination of renal function in patients with intestinal urinary diversions

    SciTech Connect

    McDougal, W.S.; Koch, M.O.

    1986-06-01

    The regular determination of renal function is a critical part of the management of patients who have had the urinary tract reconstructed with intestinal segments. These intestinal segments reabsorb urinary solutes and, thereby, complicate the determination of renal function by conventional methods. Urinary clearances of urea, creatinine and inulin were performed in patients with intestinal segments in the urinary tract and controls under varying diuretic conditions. Patients with intestinal diversions also underwent radioisotopic determination of renal function. The urinary clearances of urea, creatinine and inulin are highly dependent on the rate of urine flow in patients with intestinal segments in the urinary tract. Diuresis maximizes the urinary clearances of these solutes by minimizing intestinal reabsorption. Creatinine clearance prediction from the serum creatinine underestimates true glomerular filtration rate. Radioisotopic determination of renal function correlates poorly with true glomerular filtration rate. Only creatinine clearance measured under diuretic conditions correlates well with true renal function. Urine concentrating ability cannot be assessed accurately in patients with intestinal segments in the urinary tract, since osmolality rapidly equilibrates across the segments.

  2. Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium.

    PubMed

    Hou, Jianghui; Shan, Qixian; Wang, Tong; Gomes, Antonio S; Yan, QingShang; Paul, David L; Bleich, Markus; Goodenough, Daniel A

    2007-06-08

    Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a human disorder caused by mutations in the tight junction protein claudin-16. However, the molecular mechanisms underlining the renal handling of magnesium and its dysfunction causing FHHNC are unknown. Here we show that claudin-16 plays a key role in maintaining the paracellular cation selectivity of the thick ascending limbs of the nephron. Using RNA interference, we have generated claudin-16-deficient mouse models. Claudin-16 knock-down (KD) mice exhibit chronic renal wasting of magnesium and calcium and develop renal nephrocalcinosis. Our data suggest that claudin-16 forms a non-selective paracellular cation channel, rather than a selective Mg(2+)/Ca(2+) channel as previously proposed. Our study highlights the pivotal importance of the tight junction in renal control of ion homeostasis and provides answer to the pathogenesis of FHHNC. We anticipate our study to be a starting point for more sophisticated in vivo analysis of tight junction proteins in renal functions. Furthermore, tight junction proteins could be major targets of drug development for electrolyte disorders.

  3. Applications of urinary proteomics in renal disease research using animal models.

    PubMed

    Lv, Yang; Cai, Guangyan; Chen, Xiangmei

    2015-01-01

    Animal models of renal disease are essential tools in research on kidney disease and have provided valuable insights into pathogenesis. Use of animal models minimises inter-individual differences, allows specific pathological changes to be examined, and facilitates collection of tissue samples. Thus, mechanistic research and identification of biomarkers are possible. Various animal models manifesting specific pathological lesions can be used to investigate acute or chronic kidney disease (CKD). Urine, a terminal metabolic product, is produced via glomerular filtration, reabsorption, and excretion in the tubular and collecting ducts, reflecting the functions of glomeruli or tubular tissue stimulated in various ways or subject to disease. Almost 70 % of urinary proteins originate from the kidney (the other 30 % come from plasma), and urinary sampling is important to noninvasively detect renal disease. Proteomics is powerful when used to screen urine components. Increasingly, urine proteomics is used to explore the pathogenesis of kidney disease in animals and to identify novel biomarkers of renal disease. In this section, we will introduce the field of urinary proteomics as applied in different models of animal renal disease and the valuable role played by proteomics in noninvasive diagnosis and rational treatment of human renal disease.

  4. The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats.

    PubMed

    Schürch, Regula; Todesco, Liliane; Novakova, Katarina; Mevissen, Meike; Stieger, Bruno; Krähenbühl, Stephan

    2010-06-10

    Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma carnitine and with a 74% decrease in the skeletal muscle carnitine content. In contrast, treatment with L-carnitine increased plasma carnitine levels by 80% and the skeletal muscle carnitine content by 50%. Treatment with L-carnitine affected neither the activity of carnitine transport into isolated renal brush border membrane vesicles, nor renal mRNA expression of the carnitine transporter OCTN2. In contrast, in carnitine deficient rats, carnitine transport into isolated brush border membrane vesicles was increased 1.9-fold compared to untreated control rats. Similarly, renal mRNA expression of OCTN2 increased by a factor of 1.7 in carnitine deficient rats, whereas OCTN2 mRNA expression remained unchanged in gut, liver or skeletal muscle. Our study supports the hypothesis that a decrease in the carnitine plasma and/or glomerular filtrate concentration increases renal expression and activity of OCTN2.

  5. Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

    PubMed

    Wang, Jing; Wen, Yubing; Zhou, Mengyu; Shi, Xiaoxiao; Jiang, Lanping; Li, Mingxi; Yu, Yang; Li, Xuemei; Li, Xuewang; Zhang, Wen; Lundquist, Andrew L; Chen, Limeng

    2017-06-02

    This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21(+) follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.

  6. The link in Linking

    PubMed Central

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  7. The link in Linking.

    PubMed

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-05-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block.

  8. ACCESSORY RENAL VESSELS

    PubMed Central

    Ali Mohammed, Ammar Mohammed; Elseed Abdalrasol, Rami Gusm; Alamin Abdalhai, Khatim; Gommaa Hamad, Mohamed

    2012-01-01

    Knowledge of the variations of the renal artery has grown in importance with increasing of renal transplants, vascular reconstructions and various surgical and radiologic techniques performing in recent years. We report the presence of unilateral doubled renal vessels, discovered on routine dissection of a male cadaver, on the right side; additional renal artery originated from the abdominal aorta. In addition the right suprarenal gland received arteries from right renal and inferior phrenic arteries only. The right inferior phrenic originated from the right renal artery. PMID:23322980

  9. Tumor Enucleation for Renal Cell Carcinoma

    PubMed Central

    Malkowicz, S. Bruce

    2015-01-01

    The increased number of small renal masses (SRMs) detected annually has led to a rise in the use of nephron-sparing surgery (NSS). These techniques aim to preserve the largest amount of healthy renal tissue possible while maintaining the same oncologic outcomes as radical nephrectomy (RN). Additionally, partial nephrectomy (PN) has been linked to a lower risk of chronic kidney disease, cardiovascular morbidity, and mortality when compared to RN. There has been continual progress toward resecting less renal parenchyma. While the predominant surgical method of performing NSS is through traditional PN, simple enucleation (SE) of the tumor has increased in popularity over recent years. SE is a technique that aims to preserve the maximal amount of renal parenchyma possible by utilizing the renal tumor pseudocapsule to bluntly separate the lesion from its underlying parenchyma, offering the smallest possible margin of excised healthy renal tissue. Several studies have demonstrated the oncological safety of SE compared with PN in the treatment of SRMs, with lower overall incidence of positive surgical margins. Additionally, SE has been shown to have similar 5- and 10-year progression-free and cancer-specific survival as PN. We present a review of the literature and an argument for SE to be a routine consideration in the treatment of all renal tumors amenable to NSS.

  10. Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors in type 2 diabetes mellitus.

    PubMed

    Tejedor Jorge, Alberto

    2016-11-01

    In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron. As a result, the glomerular vasodilation caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration, and c) the excess glucose transported to the proximal tubular cells modifies their redox status, increasing local production of glycosylating products and activating local production of proinflammatory and profibrotic proliferative mediators. These mediators are responsible for the direct free radical damage to proximal tubular cells, for increased SGLT2 expression, increased production of collagen IV and extracellular matrix, and activation of monocyte/macrophages able to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the reabsorption of glucose from the glomerular filtrate back into the circulationthus improving metabolic control in diabetesbut also restores tubuloglomerular feedback by increasing glycosuria and distal urinary flow. However, the most notable effect is due to inhibition of glucose entry to the proximal tubular cells. Glycosuria is toxic to the kidney: it harms glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In animal models, SGLT2 inhibition reduces local production of oxygen-free radicals, the formation of mesangial matrix and collagen IV

  11. Melamine Impairs Renal and Vascular Function in Rats

    PubMed Central

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-01-01

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576

  12. Melamine Impairs Renal and Vascular Function in Rats.

    PubMed

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-06-21

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.

  13. Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds.

    PubMed

    Udy, Andrew A; Jarrett, Paul; Stuart, Janine; Lassig-Smith, Melissa; Starr, Therese; Dunlop, Rachel; Wallis, Steven C; Roberts, Jason A; Lipman, Jeffrey

    2014-11-29

    The aim of this study was to explore changes in glomerular filtration (GFR) and renal tubular function in critically ill patients at risk of augmented renal clearance (ARC), using exogenous marker compounds. This prospective, observational pharmacokinetic (PK) study was performed in a university-affiliated, tertiary-level, adult intensive care unit (ICU). Patients aged less than or equal to 60 years, manifesting a systemic inflammatory response, with an expected ICU length of stay more than 24 hours, no evidence of acute renal impairment (plasma creatinine concentration < 120 μmol/L) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion. The following study markers were administered concurrently: sinistrin 2,500 mg (Inutest; Laevosan, Linz, Austria), p-aminohippuric acid (PAH) 440 mg (4% p-aminohippuric acid sodium salt; CFM Oskar Tropitzsch, Marktredwitz, Germany), rac-pindolol 5 or 15 mg (Barbloc; Alphapharm, Millers Point, NSW, Australia) and fluconazole 100 mg (Diflucan; Pfizer Australia Pty Ltd, West Ryde, NSW, Australia). Plasma concentrations were then measured at 5, 10, 15, 30, 60 and 120 minutes and 4, 6, 12 and 24 hours post-administration. Non-compartmental PK analysis was used to quantify GFR, tubular secretion and tubular reabsorption. Twenty patients were included in the study. Marker administration was well tolerated, with no adverse events reported. Sinistrin clearance as a marker of GFR was significantly elevated (mean, 180 (95% confidence interval (CI), 141 to 219) ml/min) and correlated well with creatinine clearance (r = 0.70, P < 0.01). Net tubular secretion of PAH, a marker of tubular anion secretion, was also elevated (mean, 428 (95% CI, 306 to 550) ml/min), as was net tubular reabsorption of fluconazole (mean, 135 (95% CI, 100 to 169) ml/min). Net tubular secretion of (S)- and (R)-pinodolol, a marker of tubular cation secretion, was impaired. In critically ill patients at risk of ARC, significant

  14. Renal cell cancer and exposure to gasoline: A review

    SciTech Connect

    McLaughlin, J.K.

    1993-12-01

    A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. 48 refs.

  15. Kidney (Renal) Failure

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

  16. Primary renal carcinoid tumor.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Suthar, K S; Kute, V B; Modi, P R; Trivedi, H L

    2013-09-01

    Primary renal carcinoid tumor is extremely rare and, therefore, its pathogenesis and prognosis is not well known. We report a primary renal carcinoid in a 26-year-old man treated by radical nephrectomy.

  17. Renal arteries (image)

    MedlinePlus

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  18. Renal vein thrombosis

    MedlinePlus

    ... the kidneys. Possible Complications Complications may include: Acute renal failure (especially if thrombosis occurs in a dehydrated child) ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood ... embolus Renal Tumor Review Date 5/19/2015 Updated by: ...

  19. [Capacities of examination of renal function at excretory urography].

    PubMed

    Bosin, V Iu; Zyrianov, V Iu

    2004-01-01

    The study was undertaken to enhance the diagnostic capacities of excretory urography in evaluating renal function, by determining the renal clearance of a contrast medium. The main task of the study was to develop bloodless and rather reliable ways of estimating the volume of the body's distributed contrast medium and its urinary concentration in the patient at urography. Excretory urography was performed in 248 patients aged 12 to 75 years. The specific gravity of excreted urine was determined with a standard laboratory urometer to 0.001 g/cm3. Absoption spectrophotometry was used to determine the serum concentration of contrast medium in 67 patients. The values of concentrations were plotted in the semilogarithmic ordinate system, followed by extrapolation of the initial segment of the plot to the so-called zero point determining the value of the concentration of contrast medium at the moment of its complete distribution in the intercellular space. The derived value was compared with the medium's dose coming into the body, which made it possible to determine the degree of dilution of the substance, i.e. the volume of its distribution in the organism. There was a linear relationship between the concentrations of renally eliminated contrast medium and the specific gravity of excreted urine. The numerical value of the constant reflecting this relationship is equal to 6. There was evidence for that such studies could be made by routine urometry. A high correlation was found between the body mass and the volume of distribution of contrast medium in the intercellular space. The discovery of the above regularities permitted the procedure for measuring the values of two most important physiological renal process (glomerular filtration and trabecular water reabsorption) to be simplified and widely available. The paper outlines the great promises for using excretory urography as a scanning functional test during a primary study and a follow-up of the patient's status.

  20. Renal Denervation

    PubMed Central

    Pan, Tao; Guo, Jin-he; Teng, Gao-jun

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015. Studies were included if a statistical relationship was investigated between RDN and T2DM. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles. In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity. Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded. If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies

  1. Renal disease in pregnancy.

    PubMed

    Sanders, C L; Lucas, M J

    2001-09-01

    Women with renal disease who conceive and continue a pregnancy are at significant risk for adverse maternal and fetal outcomes. Risk is inversely related to the degree of renal insufficiency. Pregnancy-induced changes in the urinary tract can temporarily increase renal function compromise, such as nephrosis, but most often results in no net increase in dysfunction. Common complications of pregnancy--such as hypertension and hypovolemia--can be associated with acute renal injury or aggravation of pre-existing disease.

  2. [Idiopathic renal arteriovenous fistula].

    PubMed

    Bennani, S; Ait Bolbarod, A; el Mrini, M; Kadiri, R; Benjelloun, S

    1996-06-01

    The authors report a case of idiopathic renal arteriovenous fistula. The diagnosis was established angiographically in a 24 year old man presenting gross hematuria. Embolization of the fistula was performed. Efficiency of this treatment was appreciated clinically and by duplex renal ultrasonography. The characteristics of renal arteriovenous fistulas are reviewed.

  3. Cardio-renal syndrome

    PubMed Central

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome. PMID:27635229

  4. [Renal leiomyoma. Case report].

    PubMed

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  5. Alteration of renal function of rats following spaceflight.

    PubMed

    Wade, C E; Morey-Holton, E

    1998-10-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  6. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  7. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  8. Link direction for link prediction

    NASA Astrophysics Data System (ADS)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-03-01

    Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

  9. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies

    PubMed Central

    Haque, Syed K.; Ariceta, Gema; Batlle, Daniel

    2012-01-01

    Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO3 in the proximal tubule. This is usually manifested as bicarbonate wastage in the urine reflecting that the defect in proximal tubular transport is severe enough that the capacity for bicarbonate reabsorption in the thick ascending limb of Henle's loop and more distal nephron segments is overwhelmed. More subtle defects in proximal bicarbonate transport likely go clinically unrecognized owing to compensatory reabsorption of bicarbonate distally. Inherited proximal RTA is more commonly autosomal recessive and has been associated with mutations in the basolateral sodium-bicarbonate cotransporter (NBCe1). Mutations in this transporter lead to reduced activity and/or trafficking, thus disrupting the normal bicarbonate reabsorption process of the proximal tubules. As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with the Fanconi syndrome characterized by urinary wastage of solutes like phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins as well as bicarbonate. A vast array of rare tubular disorders may cause proximal RTA but most commonly it is induced by drugs. With the exception of carbonic anhydrase inhibitors which cause isolated proximal RTA, drug-induced proximal RTA is associated with Fanconi syndrome. Drugs that have been recently recognized to cause severe proximal RTA with Fanconi syndrome include ifosfamide, valproic acid and various antiretrovirals such as Tenofovir particularly when given to human immunodeficiency virus patients receiving concomitantly protease inhibitors such as ritonavir or reverse transcriptase inhibitors such as didanosine. PMID:23235953

  10. Renal function in sheep during infusion of alkali metal ions into the renal artery.

    PubMed Central

    Beal, A M; Harrison, F A

    1975-01-01

    1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

  11. Serum Parathyroid Hormone Levels and Renal Handling of Phosphorus in Patients with Chronic Renal Disease

    PubMed Central

    Popovtzer, Mordecai M.; Pinggera, Wulf F.; Hutt, Martin P.; Robinette, John; Halgrimson, Charles G.; Starzl, Thomas E.

    2010-01-01

    In eight patients with advanced renal insufficiency (inulin clearance 1.4–9.1 ml/min), concentrations of serum calcium (S[Ca]) and phosphorus (S[P]) were maintained normal (S[Ca] > 9.0 mg/100 ml, (S[P] < 3.5 mg/100 ml) for at least 20 consecutive days with phosphate binding antacids and oral calcium carbonate. The initial serum levels of immunoreactive parathyroid hormone (S-PTH) were elevated in three (426–9230 pg/ml), normal in four (one after subtotal parathyroidectomy), and not available in one. The initial fractional excretion of filtered phosphorus (CpCIN) was high in all and ranged from 0.45–1.05. Following sustained normo-calcemia and normo-phosphatemia, S-PTH was reduced below control levels in all patients; being normal in six and elevated in two. CpCIN decreased below control levels in all patients; it remained high in six (of which five had normal S-PTH) and was normal (CpCIN=0.01) in two (of which one had elevated S-PTH). The observed relationship between S-PTH and CpCIN could either reflect the inability of the radioimmunoassay for PTH employed to measure a circulating molecular species of PTH which was present in which case the actual levels of S-PTH were higher than those measured, and/or it could be indicative of the presence of additional important factor(s) (other than S-PTH) which inhibit tubular reabsorption of phosphorus in advanced chronic renal failure. PMID:4672382

  12. Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

    PubMed Central

    Subramanian, Veedamali S.; Subramanya, Sandeep B.; Ghosal, Abhisek

    2013-01-01

    Vitamin B2 (riboflavin, RF) is essential for normal human health. Mammals obtain RF from exogenous sources via intestinal absorption and prevent its urinary loss by reabsorption in the kidneys. Both of these absorptive events are carrier-mediated and involve specific RF transporters (RFVTs). Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels, but little is known about the effect of chronic alcohol exposure on physiological and molecular parameters of the intestinal and renal RF transport events. We addressed these issues using rats chronically fed an alcohol liquid diet and pair-fed controls as a model. The results showed that chronic alcohol feeding significantly inhibits carrier-mediated RF transport across the intestinal brush-border and basolateral membrane domains of the polarized enterocytes. This inhibition was associated with a parallel reduction in the expression of the rat RFVT-1 and -3 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Chronic alcohol feeding also caused a significant inhibition in RF uptake in the colon. Similarly, a significant inhibition in carrier-mediated RF transport across the renal brush-border and basolateral membrane domains was observed, which again was associated with a significant reduction in the level of expression of RFVT-1 and -3 at the protein, mRNA, and hnRNA levels. These findings demonstrate that chronic alcohol exposure impairs both intestinal absorption and renal reabsorption processes of RF and that these effects are, at least in part, mediated via transcriptional mechanism(s) involving the slc52a1 and slc52a3 genes. PMID:23804199

  13. Effect of Adrenalectomy on the Renal Response to Chloride Depletion in the Rat

    PubMed Central

    Luke, R. G.

    1974-01-01

    These experiments were aimed at investigating renal behavior towards chloride, as distinct from sodium, during dietary deprivation of these ions in adrenalectomized rats. Adrenalectomized and shamoperated control rats were maintained on saline for 3 wk, then chloride conservation during a very low chloride intake was assessed both with an abundant sodium intake (as buffered sodium phosphate in the drinking water) and after subsequent withdrawal of sodium. When sodium intake was high, there was no difference in chloride conservation between adrenalectomized and control animals, and sodium balance and weight were maintained similarly in both groups. At the same time, both experimental and control rats developed significant hypokalemia and elevation of the plasma bicarbonate levels as compared to other control rats ingesting a normal diet. In another group of adrenalectomized rats sodium phosphate was withdrawn, after normal chloride conservation was observed, and the low-salt diet continued. Negative sodium balance developed and was associated with a negative chloride balance, whereas sham-operated rats continued to conserve sodium and chloride. In further studies during polyuria, both adrenalectomized and control rats developed urinary chloride concentrations of less than 1 meq/liter. Thus adrenalectomized rats can maintain chloride balance on a low chloride, high sodium intake, in contrast to their inability to conserve sodium on a low-sodium intake. It is concluded that renal tubular reabsorption of chloride in adrenalectomized rats is adequate to establish and maintain very low urinary chloride concentrations, which may imply active chloride transport in the papillary collecting duct despite the absence of adrenocortical hormone. In addition, the typical renal response to chloride deprivation, enhanced loss of potassium and accelerated reabsorption of bicarbonate, is not dependent on adrenocortical hormones. PMID:4436435

  14. Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport.

    PubMed

    Subramanian, Veedamali S; Subramanya, Sandeep B; Ghosal, Abhisek; Said, Hamid M

    2013-09-01

    Vitamin B2 (riboflavin, RF) is essential for normal human health. Mammals obtain RF from exogenous sources via intestinal absorption and prevent its urinary loss by reabsorption in the kidneys. Both of these absorptive events are carrier-mediated and involve specific RF transporters (RFVTs). Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels, but little is known about the effect of chronic alcohol exposure on physiological and molecular parameters of the intestinal and renal RF transport events. We addressed these issues using rats chronically fed an alcohol liquid diet and pair-fed controls as a model. The results showed that chronic alcohol feeding significantly inhibits carrier-mediated RF transport across the intestinal brush-border and basolateral membrane domains of the polarized enterocytes. This inhibition was associated with a parallel reduction in the expression of the rat RFVT-1 and -3 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Chronic alcohol feeding also caused a significant inhibition in RF uptake in the colon. Similarly, a significant inhibition in carrier-mediated RF transport across the renal brush-border and basolateral membrane domains was observed, which again was associated with a significant reduction in the level of expression of RFVT-1 and -3 at the protein, mRNA, and hnRNA levels. These findings demonstrate that chronic alcohol exposure impairs both intestinal absorption and renal reabsorption processes of RF and that these effects are, at least in part, mediated via transcriptional mechanism(s) involving the slc52a1 and slc52a3 genes.

  15. Renal artery aneurysms.

    PubMed

    González, J; Esteban, M; Andrés, G; Linares, E; Martínez-Salamanca, J I

    2014-01-01

    A renal artery aneurysm is defined as a dilated segment of renal artery that exceeds twice the diameter of a normal renal artery. Although rare, the diagnosis and incidence of this entity have been steadily increasing due to the routine use of cross-sectional imaging. In certain cases, renal artery aneurysms may be clinically important and potentially lethal. However, knowledge of their occurrence, their natural history, and their prognosis with or without treatment is still limited. This article aims to review the recent literature concerning renal artery aneurysms, with special consideration given to physiopathology, indications for treatment, different technical options, post-procedure complications and treatment outcomes.

  16. An experimental renal acidification defect in patients with hereditary fructose intolerance. I. Its resemblance to renal tubular acidosis.

    PubMed

    Morris, R C

    1968-06-01

    In three unrelated patients with hereditary fructose intolerance (HFI), but in none of five normal subjects, the experimental administration of fructose invariably induced a reversible dysfunction of the renal tubule with biochemical and physiological characteristics of renal tubular acidosis. During a state of ammonium chloride-induced acidosis, (a) urinary pH was greater than six and the rate of excretion of net acid (titratable acid plus ammonium minus bicarbonate) was inappropriately low, (b) the glomerular filtration rate remained unchanged or decreased modestly, and (c) urinary excretion of titratable acid increased briskly with diuresis of infused phosphate, although urinary pH changed little. The tubular dysfunction, which also includes impaired tubular reabsorption of alpha amino nitrogen and phosphate, persisted throughout administration of fructose and disappeared afterward. The tubular dysfunction was not causally dependent on hypoglucosemia, ammonium chloride-induced acidosis or osmotic diuresis. Rather, it appeared causally related to the fructose-induced metabolic abnormality of patients with HFI. The causal enzymatic defect, the virtual absence of fructose-1-phosphate aldolase, occurs in the kidney as well as in the liver of patients with HFI.

  17. Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: high-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies.

    PubMed

    Ishida, H; Tanabe, K; Furusawa, M; Isizuka, T; Tokumoto, T; Shimmura, H; Shimizu, T; Miyamoto, N; Hayashi, T; Toma, H

    2004-09-01

    We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral rejection after ABO-incompatible renal transplantation. High agglutinin IgG and IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular rejection were separately assessed using an ELISA. Patients who exhibited excellent renal function despite high agglutinin titers of anti-blood-type antibodies(n = 8) were also examined. All 12 rejection patients exhibited highly elevated titers of IgG and IgM, while the eight stable patients exhibited only slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change after plasmapheresis and steroid pulse therapy, whereas IVIg treatment significantly blocked both IgG and IgM, with IgM being blocked to a larger extent than IgG. Blocking of IgM seems to play an important role in improving ABO-incompatible grafts.

  18. In vivo and in vitro studies on renal uptake of radiolabeled affibody molecules for imaging of HER2 expression in tumors.

    PubMed

    Altai, Mohamed; Varasteh, Zohreh; Andersson, Karl; Eek, Annemarie; Boerman, Otto; Orlova, Anna

    2013-04-01

    Affibody molecules (6-7 kDa) are a new class of small robust three-helical scaffold proteins. Radiolabeled subnanomolar anti-HER2 affibody ZHER2:342 was developed for imaging of HER2 expression in tumors, and a clinical study has demonstrated that the (111)In- and (68)Ga-labeled affibody molecules can efficiently detect HER2 expressing metastases in breast cancer patients. However, a significant renal accumulation of radioactivity after systemic injection of a radiolabeled anti-HER2 affibody conjugate is observed. The aim of this study was to investigate the mechanism of renal reabsorption of anti-HER2 affibody at the molecular level. Renal accumulation of radiolabeled anti-HER2 affibody molecules was studied in a murine model and in vitro using opossum-derived proximal tubule (OK) cells. It was found that kidney reabsorption of affibody molecule was not driven by megalin/cubilin. Amino acids in the target-binding side of affibody molecule were involved in binding to OK cells. On OK cells, two types of receptors for anti-HER2 affibody molecule were found: KD1=0.8 nM, Bmax1=71,500 and KD2=9.2 nM, Bmax2=367,000. The results of the present study indicate that affibody molecule and other scaffold-based targeting proteins with a relatively low kidney uptake can be selected using in vitro studies with tubular kidney cells.

  19. Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin.

    PubMed

    Gburek, Jakub; Birn, Henrik; Verroust, Pierre J; Goj, Bogusława; Jacobsen, Christian; Moestrup, Søren K; Willnow, Thomas E; Christensen, Erik I

    2003-09-01

    Nephrotoxicity of myoglobin is well recognized as playing a part in the development of acute renal failure in settings of myoglobinuria. However, the molecular mechanism of myoglobin uptake in renal proximal tubules has not been clarified. Here, we report that the endocytic receptors megalin and cubilin are involved in renal reabsorption of myoglobin. Both receptors were captured from solubilized renal brush-border membranes by affinity chromatography using myoglobin-Sepharose. Myoglobin bound to purified megalin and cubilin with Kd values of 2.0 and 3 microM, respectively, as evaluated by surface plasmon resonance analysis. Apomyoglobin bound to megalin with the same affinity, and the affinity of apomyoglobin to cubilin was reduced (Kd = 5 microM). Radioiodinated myoglobin could be displaced by apomyoglobin in inhibition studies using isolated renal brush-border membranes (Ki approximately 2 microM). Receptor-associated protein as well as antibodies directed against megalin and cubilin markedly inhibited the uptake of fluorescent-labeled myoglobin by cultured yolk sac BN-16 cells. The significance of megalin- and cubilin-mediated endocytosis for myoglobin uptake in vivo was demonstrated by use of kidney-specific megalin knockout mice. Injected myoglobin was extensively reabsorbed by megalin-expressing proximal tubular cells, whereas there was very little uptake in the megalin-deficient cells. In conclusion, this study establishes the molecular mechanism of myoglobin uptake in the renal proximal tubule involving the endocytic receptors megalin and cubilin. Identification of the receptors for tubular uptake of myoglobin may be essential for development of new therapeutic strategies for myoglobinuric acute renal failure.

  20. Renal Xenobiotic Transporters are Differentially Expressed In Mice Following Cisplatin Treatment

    PubMed Central

    Aleksunes, Lauren M; Augustine, Lisa M; Scheffer, George L; Cherrington, Nathan J; Manautou, José E

    2008-01-01

    The goal of this study was to identify alterations in mRNA and protein expression of various xenobiotic transport proteins in mouse kidney during cisplatin-induced acute renal failure. For this purpose, male C57BL/6J mice received a single dose of cisplatin (18 mg/kg, ip) or vehicle. Four days later, tissues were collected for assessment of plasma BUN, histopathological analysis of renal lesions, and mRNA and western blot analysis of renal transporters including organic anion and cation transporters (Oat, Oct), organic anion transporting polypeptides (Oatp), multidrug resistance-associated proteins (Mrp), multidrug resistance proteins (Mdr), breast cancer resistance protein (Bcrp) and multidrug and toxin extrusion proteins (Mate). Cisplatin treatment caused necrosis of renal proximal tubules along with elevated plasma BUN and renal kidney injury molecule-1 mRNA expression. Cisplatin-induced renal injury increased mRNA and protein levels of the efflux transporters Mrp2, Mrp4, Mrp5, Mdr1a and Mdr1b. Uptake transporters Oatp2a1 and Oatp2b1 mRNA were also up-regulated following cisplatin. By contrast, expression of Oat1, Oat2, Oct2 and Oatp1a1 mRNA was reduced in cisplatin-treated mice. Expression of several uptake and efflux transporters was unchanged in cisplatin-treated mice. Apical staining of Mrp2 and Mrp4 proteins was enhanced in proximal tubules from cisplatin-treated mice. Collectively, these expression patterns suggest coordinated regulation of uptake and efflux pathways during cisplatin-induced renal injury. Reduced expression of basolateral and apical uptake transporters along with enhanced transcription of export transporters likely represents an adaptation to lower intracellular accumulation of chemicals, prevent their reabsorption and enhance urinary clearance. PMID:18640236

  1. Effects of acute sodium fluoride exposure on kidney function, water homeostasis, and renal handling of calcium and inorganic phosphate.

    PubMed

    Santoyo-Sanchez, Mitzi Paola; del Carmen Silva-Lucero, Maria; Arreola-Mendoza, Laura; Barbier, Olivier Christophe

    2013-06-01

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.

  2. Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction.

    PubMed

    Nieskens, Tom T G; Wilmer, Martijn J

    2016-11-05

    The renal proximal tubule epithelium is responsible for active secretion of endogenous and exogenous waste products from the body and simultaneous reabsorption of vital compounds from the glomerular filtrate. The complexity of this transport machinery makes investigation of processes such as tubular drug secretion a continuous challenge for researchers. Currently available renal cell culture models often lack sufficient physiological relevance and reliability. Introducing complex biological culture systems in a 3D microfluidic design improves the physiological relevance of in vitro renal proximal tubule epithelium models. Organ-on-a-chip technology provides a promising alternative, as it allows the reconstruction of a renal tubule structure. These microfluidic systems mimic the in vivo microenvironment including multi-compartmentalization and exposure to fluid shear stress. Increasing data supports that fluid shear stress impacts the phenotype and functionality of proximal tubule cultures, for which we provide an extensive background. In this review, we discuss recent developments of kidney-on-a-chip platforms with current and future applications. The improved proximal tubule functionality using 3D microfluidic systems is placed in perspective of investigating cellular signalling that can elucidate mechanistic aberrations involved in drug-induced kidney toxicity. Copyright © 2016. Published by Elsevier B.V.

  3. Role of renal nerves in compensatory adaptation to chronic reductions in sodium intake

    SciTech Connect

    Mizelle, H.L.; Hall, J.E.; Woods, L.L.; Montani, J.P.; Dzielak, D.J.; Pan, Y.J.

    1987-02-01

    The aim of this study was to investigate the importance of the renal nerves in adaptation to chronic reductions in sodium intake. Conscious dogs with unilateral or bilateral renal denervation were studied. Kidney function was determined by the clearance (/sup 125/I)-contrast media. In dogs studied before and after bilateral denervation, there were no differences in urine volume (UO), Na excretion (U/sub Na/V), or fractional reabsorption of Li, between innervated and denervated kidneys on either normal (80 meg/day) or low Na intake (5 meq/day, 15 days). Plasma renin activity (PRA) was attenuated following denervation on both normal and low Na intake. There was no difference in UO between innervated and denervated kidneys on normal or low Na intake. U/sub Na/V averaged 33.6 +/- 1.3 and 37.6 +/- 2.1 meq/day in innervated and denervated kidneys, respectively, on normal Na intake and 3.5 +/- 0.5 and 4.0 +/- 0.4 meq/day in innervated and denervated kidneys on low Na intake. Norepinephrine content was reduced by 99 +/- 1% in denervated kidneys. These results suggest that, although the renal nerves may play a small role in controlling U/sub Na/V during normal Na, the presence of the nerves is not essential for adaptation to chronic reductions in Na intake. However, the renal nerves may play a role in long-term control of renin secretion.

  4. Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake

    SciTech Connect

    de Lange, M.J.; Piers, D.A.; Kosterink, J.G.; van Luijk, W.H.; Meijer, S.; de Zeeuw, D.; van der Hem, G.K.

    1989-07-01

    The finding of an enhanced excretion of (/sup 99m/Tc)dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of (/sup 99m/Tc)DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of (/sup 99m/Tc)DMSA in a human volunteer was 5.8%. Continuous infusion of (/sup 99m/Tc)DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of (/sup 99m/Tc)DMSA 34 +/- 4 ml/min, urinary clearance of (/sup 99m/Tc)DMSA 12 +/- 3 ml/min. The calculated filtered load of (/sup 99m/Tc)DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of (/sup 99m/Tc)DMSA.

  5. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  6. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  7. Water balance and renal function in two species of African lungfish Protopterus dolloi and Protopterus annectens.

    PubMed

    Patel, Monika; Iftikar, Fathima I; Smith, Richard W; Ip, Yuen K; Wood, Chris M

    2009-02-01

    The basic physiology of water balance and kidney function was characterized in two species of African lungfish, Protopterus dolloi and Protopterus annectens. Diffusive water efflux rate constants were low (0.13 h(-1)-0.38 h(-1) in various series) relative to values in freshwater teleost fish. Efflux rate constants increased approximately 3-fold after feeding in both species, and were greatly decreased after 8 months terrestrialization (P. dolloi only tested). Urine flow rates (UFR, 3.9-5.2 mL kg(-1) h(-1)) and glomerular filtration rates (GFR, 6.6-9.3 mL kg(-1) h(-1)) were quite high relative to values in most freshwater teleosts. However urinary ion excretion rates were low, with net re-absorption of >99% Na(+), >98% Cl(-), and >78% Ca(2+) from the primary filtrate, comparable to teleosts. Net water re-absorption was significantly greater in P. dolloi (56%) than in P. annectens (23%). We conclude that renal function in lungfish is similar to that in other primitive freshwater fish, but there is an interesting dichotomy between diffusive and osmotic permeabilities. Aquatic lungfish have low diffusive water permeability, an important pre-adaptation to life on land, and in accord with greatly reduced gill areas and low metabolic rates. However osmotic permeability is high, 4-12 times greater than diffusive permeability. A role for aquaporins in this dichotomy is speculated.

  8. Renal phosphate transport: inhomogeneity of local proximal transport rates and sodium dependence.

    PubMed

    Baumann, K; de Rouffignac, C; Roinel, N; Rumrich, G; Ullrich, K J

    1975-01-01

    The standing droplet method has been used in combination with the peritibular perfusion of blood capillaries to determine the build up of transtubular concentration differences of phosphate (Piota) in the renal proximal convoluted tubule of parathyroidectomized rats. Electron probe analysis was used to estimate Piota. At zero time both the intraluminal and the contraluminal Piota concentration was 2 mM. The time dependent decrease of the intraluminal Piota concentration was approximately 4 times faster in the early than in the late proximal convoluted tubule. After 45 sec an intraluminal steady state concentration of 0.20 mM Piota was achieved in the early part. In the late part the intraluminal Piota concentration approached a steady statevalue of 0.54 mM at 123 sec. When sodium free solutions were used the intaluminal Piota concentration increased to 2.22 mM in the earlier and to 2.76 mM in the late part. The data indicate that in the proximal convoluted tubule 1. the rate of phosphate reabsorption is greater in the early part than in the later part, and 2. phospate reabsorption might occur as co-transport with Na+ ions.

  9. Forging Links.

    ERIC Educational Resources Information Center

    Stewig, John Warren

    Blacksmiths and their craft have changed with the times, and as times change for teachers, they too should be forgers of links. Teacher-to-teacher links should extend beyond the faculty lounge to support systems and active groups of individuals concerned about each other. Another personal link can be made by developing a grade level, system-wide…

  10. Renal replacement therapy for acute renal failure.

    PubMed

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  11. Renal scintiscanning. A review

    PubMed Central

    Davies, E. Rhys

    1970-01-01

    Renal scintiscanning is a simple investigation that does not require special preparation and is well tolerated by patients. Radiopharmaceuticals used in linear scanning are accumulated in the renal cortex. This accumulation is diminished: (a) when the cortex is destroyed, e.g. by pyelonephritis, injury, etc.; and (b) when the amount available to the cortex is reduced, e.g. by ischaemia. The scintigram depicts the kidneys unimpeded by bowel contents, gives a qualitative assessment of renal function and shows the distribution of zones of normal function. Recent technical improvements show great promise in deriving a quantitative measure of renal function in some circumstances. The location of normally functioning cortex is often important in the management of renal diseases and the value of scintiscanning is then considerable. It is occasionally useful in planning surgery. The anatomy of the renal collecting system can be shown only by urography. High dose techniques achieve this even in the face of renal failure, and scintiscanning has few indications in investigating lesions that distort the renal anatomy, e.g. tumours and cysts. Renal scintiscanning is a very valuable additional method to urography, arteriography and renography in investigation of renal disorders. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:4905447

  12. Recurrent renal giant leiomyosarcoma

    PubMed Central

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1–2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50–60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion’s pathology from low-grade to a high-grade tumor. PMID:27436926

  13. Visualization of deep ultraviolet photons based on Förster resonance energy transfer and cascade photon reabsorption in diphenylalanine-carbon nitrides composite film

    NASA Astrophysics Data System (ADS)

    Gan, Zhixing; Zhou, Weiping; Chen, Zhihui; Wang, Huan; Di, Yunsong; Huang, Shisong

    2016-11-01

    A diphenylalanine (L-Phe-L-Phe, FF)-carbon nitride composite film is designed and fabricated to visualize the deep ultraviolet (DUV, 245-290 nm) photons. The FF film, composed of diphenylalanine molecules, doped with carbon nitrides shows blue emission under excitation of DUV light, which makes the DUV beam observable. Both Förster resonance energy transfer and cascade photon reabsorption contribute to the conversion of photon energy. First, the FF is excited by the DUV photons. On one hand, the energy transfers to the embedded carbon nitrides through nonradiative dipole-dipole couplings. On the other hand, the 284 nm photons emitted from the FF would further excite the carbon nitrides, which will finally convert to blue fluorescence. Herein, the experimental demonstration of a simple device for the visualization of high DUV fluxes is reported.

  14. Mechanism of glucocorticoid effect on renal transport of phosphate.

    PubMed

    Turner, S T; Kiebzak, G M; Dousa, T P

    1982-11-01

    We explored whether glucocorticoid administration, a known stimulus of renal gluconeogenesis (GNG), could decrease avid inorganic phosphate (Pi) reabsorption in rats stabilized on low-phosphorus diet (LPD). Rats adapted to LPD were injected with the glucocorticoid (GCD) triamcinolone acetonide (1.25 or 2.5 mg.100 g body wt-1.day-1 ip) for 2 days; they showed a profound increase in urinary excretion of Pi during the injection period. In clearance studies GCD increased the clearance and fractional excretion of Pi but did not change the filtered load of Pi. Initial "uphill" Na+-gradient (Nao+ greater than Nai+)-dependent uptake of 32Pi by luminal brush-border membrane (BBM) vesicles prepared from renal cortex of rats treated with GCD was markedly (greater than 40%) decreased compared with control rats; Na+-gradient-dependent uptake of D-[3H]glucose was not diminished. At the "equilibrium" time interval, measured at 120 min, BBM vesicles from control and GCD-treated rats did not differ in the uptake of 32Pi or D-[3H]glucose. With kinetic analysis, BBM from GCD-treated rats showed a marked decrease (-40%) in the maximum velocity (Vmax) of initial Na+-dependent 32Pi uptake, but the apparent affinity of the BBM transport system for Pi (apparent Km = 0.078 mM Pi) was not different from that of controls. Alkaline phosphatase specific activity was much lower (-40%) in BBM from GCD-treated rats compared with controls, but the activities of three other BBM enzymes (maltase, leucine aminopeptidase, and gamma-glutamyl transferase) were not different. The addition of triamcinolone to BBM in vitro had no effect on either Na+-dependent uptake of 32Pi or alkaline phosphatase activity. The rate of GNG from alpha-ketoglutarate was significantly increased in cortical slices from GCD-treated rats adapted to LPD. Also, the NAD+-to-NADH ratio was higher in the renal cortex of GCD-treated rats, although the total content of NAD [NAD+ + NADH] was not different from controls. Renal excretory

  15. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  16. Renal tubular function in children with beta-thalassemia minor.

    PubMed

    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.

  17. Bilateral Renal Lymphangiectasia.

    PubMed

    Pandya, Vaidehi K; Shah, Maulin K; Gandhi, Shruti P; Patel, Himanshu V

    2016-09-01

    Renal Lymphangiectasia (RLM) is very rare benign lymphatic malformation. It can be misdiagnosed for other cystic renal masses, most commonly polycystic kidneys. Though incidentally found in most cases, it may be the cause for hypertension and renal failure in undiagnosed patients. Here, we report a case of an adult asymptomatic male with bilateral RLM which was detected as an incidental finding on ultrasound. Confirmation by CT-scan and laboratory diagnosis of aspirated fluid was done, and patient was managed conservatively.

  18. Chromophobe cell renal carcinoma.

    PubMed

    Megumi, Y; Nishimura, K

    1998-01-01

    Chromophobe cell renal carcinoma is a recently established subtype of renal cell carcinoma. Herein we report a case of chromophobe cell renal carcinoma in a 67-year-old male patient who occasionally underwent computed tomography. In a microscopic study with hematoxylin and eosin stain, clear eosinophilic cytoplasm, and a moderately atypical nucleus were observed. And it was stained positively by Hale's colloidal iron. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. From these results, this tumor was pathologically diagnosed as chromophobe cell renal carcinoma.

  19. Endothelial Dysfunction in Renal Failure: Current Update.

    PubMed

    Radenkovic, Miroslav; Stojanovic, Marko; Prostran, Milica

    2016-01-01

    Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.

  20. Hypertensive pregnancy disorders and future renal disease.

    PubMed

    Wagner, Steven; Craici, Iasmina

    2014-10-01

    Hypertensive pregnancy disorders affect approximately 6 to 8 % of otherwise normal pregnancies. A growing body of evidence links these disorders with the future development of hypertension, coronary disease, cerebrovascular disease, and peripheral arterial disease. Larger studies associating hypertensive pregnancy to future development of renal disease have been lacking until recently, with publication of several compelling studies in the last 5 years. In this review, we will focus on the recent evidence associating hypertensive pregnancy disorders with the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD), as well as the development of microalbuminuria. We will also attempt to answer whether these renal risks are due to direct effects of hypertension during pregnancy, or whether they are due to shared environmental and genetic risk factors.

  1. Renal pelvis or ureter cancer

    MedlinePlus

    Transitional cell cancer of the renal pelvis or ureter; Kidney cancer - renal pelvis; Ureter cancer ... Cancer can grow in the urine collection system, but it is uncommon. Renal pelvis and ureter cancers ...

  2. The effect of a low-protein diet in pregnancy on offspring renal calcium handling.

    PubMed

    Ashton, Nick; Al-Wasil, Saleh H; Bond, Helen; Berry, Jacqueline L; Denton, John; Freemont, Anthony J

    2007-08-01

    Low birth weight humans and rats exposed to a low-protein diet in utero have reduced bone mineral content. Renal calcium loss during the period of rapid skeletal growth is associated with bone loss. Because young rats exposed to low protein display altered renal function, we tested the hypothesis that renal calcium excretion is perturbed in this model. Pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (low) protein throughout gestation. Using standard renal clearance techniques, Western blotting for renal calcium transport proteins, and assays for Na(+)-K(+)-ATPase activity and serum calcitropic hormones, we characterized calcium handling in 4-wk-old male offspring. Histomorphometric analyses of femurs revealed a reduction in trabecular bone mass in low-protein rats. Renal calcium (control vs. low protein: 10.4 +/- 2.1 vs. 27.6 +/- 4.5 nmol x min(-1) x 100 g body wt(-1); P < 0.01) and sodium excretion were increased, but glomerular filtration rate was reduced in low-protein animals. Total plasma calcium was reduced in low-protein rats (P < 0.01), but ionized calcium, serum calcitropic hormone concentrations, and total body calcium did not differ. There was no significant change in plasma membrane Ca(2+)-ATPase pump, epithelial calcium channel, or calbindin-D(28K) expression in low-protein rat kidneys. However, Na(+)-K(+)-ATPase activity was 36% lower (P < 0.05) in low-protein rats. These data suggest that the hypercalciuria of low-protein rats arises through a reduction in passive calcium reabsorption in the proximal tubule rather than active distal tubule uptake. This may contribute to the reduction in bone mass observed in this model.

  3. Physiology and pathophysiology of renal aquaporins.

    PubMed

    Kwon, T H; Hager, H; Nejsum, L N; Andersen, M L; Frøkiaer, J; Nielsen, S

    2001-05-01

    The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is

  4. Structural renal changes in obesity and diabetes.

    PubMed

    Amann, Kerstin; Benz, Kerstin

    2013-01-01

    Overweight, obesity, and associated diseases represent an emerging problem, not only in Western countries but also in the developing world. They are now characterized as epidemic diseases. Obesity is particularly serious because its incidence in children and adolescents increased dramatically: it is estimated that in the United States every eighth adolescent suffers from obesity, which in the long run may reduce life expectancy in the population. Apart from cardiovascular disease (ie, blood pressure, stroke, and coronary heart disease), kidney diseases also have been shown to be associated with obesity. Epidemiologic studies have indicated that obesity can be a risk factor of chronic kidney disease irrespective of the presence or absence of diabetes, arterial hypertension, and other comorbidities. More evidence is accumulated on the link between chronic kidney disease in obesity and abnormalities in adipokine secretion (hyperleptinemia, lack of adiponectin), activation of the renin-angiotensin system, chronic inflammation, endothelial dysfunction, lipid accumulation, impaired renal hemodynamics, and diminished nephron number related to body mass. In general, obesity is known to aggravate the course of many primary renal diseases such as glomerulonephritides, but also impairs renal function after kidney transplantation. Microalbuminuria, proteinuria, hyperfiltration, and impaired renal function are associated with obesity. Histologically, secondary focal segmental sclerosis has been shown to be caused particularly by obesity. Of practical purpose for clinical nephrology, loss of body weight either by lifestyle modification or bariatric surgery improves albuminuria and hyperfiltration in obese patients, making renal disease in obesity accessible for prevention programs. This review specifically addresses the pathogenesis and morphology of renal functional and particularly structural changes in obesity and associated renal disease such as diabetic nephropathy.

  5. Renal complications of Fabry disease in children.

    PubMed

    Najafian, Behzad; Mauer, Michael; Hopkin, Robert J; Svarstad, Einar

    2013-05-01

    Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis, and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges, and needs to better approach renal complications of Fabry disease in children.

  6. Renal Complications of Fabry Disease in Children

    PubMed Central

    Najafian, Behzad; Mauer, Michael; Hopkin, Robert J; Svarstad, Einar

    2013-01-01

    Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges and needs to better approach renal complications of Fabry disease in children. PMID:22898981

  7. The role of epigenetics in renal ageing.

    PubMed

    Shiels, Paul G; McGuinness, Dagmara; Eriksson, Maria; Kooman, Jeroen P; Stenvinkel, Peter

    2017-08-01

    An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects.

  8. Renal dysfunction in cirrhosis

    PubMed Central

    Urrunaga, Nathalie H.; Mindikoglu, Ayse L.; Rockey, Don C.

    2015-01-01

    Purpose of review Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. Recent findings New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver–kidney transplantation is advised. Summary Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes. PMID:25763790

  9. [Hemorrhagic bilateral renal angiomyolipoma].

    PubMed

    Benjelloun, Mohamed; Rabii, Redouane; Mezzour, Mohamed Hicham; Joual, Abdenbi; Bennani, Saâd; el Mrini, Mohamed

    2003-09-01

    Renal angiomyolipoma is a rare benign tumour, often associated with congenital diseases especially de Bourneville's tuberous sclerosis. Bilateral angiomyolipoma is exceptional. The authors report a case of bilateral renal angiomyolipoma in a 33-year-old patient presenting with haemorrhagic shock. In the light of this case and a review of the literature, the authors discuss the diagnostic and therapeutic aspects of this disease.

  10. Renal osteodystrophy and aging.

    PubMed

    Sherrard, Donald J

    2009-11-01

    The bone disease seen in our aging dialysis population is a complex mixture of osteoporosis and renal osteodystrophy. Attention must be paid to both of these issues. Hip fractures are increased with aging and this increase is further aggravated by renal failure. Preventive management with Vitamin D and bisphosphonates is reviewed.

  11. Atheroembolic renal disease.

    PubMed

    Scolari, Francesco; Ravani, Pietro

    2010-05-08

    Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder. Eosinophilia further supports the diagnosis, usually confirmed by biopsy of an affected organ or by the fundoscopic finding of cholesterol crystals in the retinal circulation. Renal and patient prognosis are poor. Treatment is mostly preventive, based on avoidance of further precipitating factors, and symptomatic, aimed to the optimum treatment of hypertension and cardiac and renal failure. Statins, which stabilise atherosclerotic plaques, should be offered to all patients. Steroids might have a role in acute or subacute progressive forms with systemic inflammation.

  12. Renal angiomyoadenomatous tumour.

    PubMed

    Jayalakshmy, P S; Jose, Merin; Feroze, M; Kumar, Rajesh K

    2017-09-01

    Renal angiomyoadenomatous tumour is a newly described rare neoplasm. This tumour is characterised microscopically by admixture of three components- epithelial cells arranged in tubules and nests, angiomyomatous stroma and capillary sized interconnecting vascular channels in close association with the epithelial cell clusters. Micr