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Sample records for links renal reabsorption

  1. Renal water reabsorption: a physiologic retrospective in a molecular era.

    PubMed

    Schafer, James A

    2004-10-01

    The cloning and sequencing of the aquaporin water channels has been an enormous advance in the biomedical sciences, as recognized by the award of the Nobel Prize to Peter Agre last year. Among many other examples, expression of aquaporin proteins in Xenopus oocytes and other heterologous expression systems has confirmed two important models of renal function: the increase in the water permeability of the collecting duct by antidiuretic hormone (ADH), and the mechanism of near isosmotic volume reabsorption by the proximal tubule. These mechanisms were the subjects of intensive investigation by numerous investigators, including Thomas E. Andreoli, who is being honored by this symposium, and who developed many of the key concepts in these areas. His early work with artificial lipid bilayer membranes and the pore-forming antibiotic amphotericin provided the rigorous foundation in experimental and conceptual modeling techniques that he later applied to physiologic and pathophysiologic mechanisms in the kidney, which are summarized in this retrospective. Dr. Andreoli and his colleagues proposed a water channel mechanism for the action of ADH, which has been confirmed by the cloning and heterologous expression of aquaporin-2. They also proposed that volume reabsorption by the proximal tubule depended on a very high hydraulic conductivity and the development of luminal hypotonicity produced by active solute reabsorption. This model has also been confirmed in mice in which aquaporin-1 expression is knocked out, resulting in a low proximal tubule water permeability that exaggerates the development of luminal hypotonicity. PMID:15461698

  2. Factors modifying renal tubular bicarbonate reabsorption in the dog

    PubMed Central

    Ullmann, Elisabeth

    1968-01-01

    1. Acute experiments were carried out on anaesthetized dogs during metabolic alkalosis produced by I.V. administration of NaHCO3. Partial constriction of one ureter led to a significant rise in the HCO3- threshold, beyond the simultaneous value for the other kidney. The magnitude of the increase was not correlated with the reduction of glomerular filtration. 2. Stop-flow analysis, following complete unilateral obstruction of urine flow, demonstrated proximal as well as distal tubular reabsorption of bicarbonate. At any given plasma Pco2 the detailed configuration of the concentration changes which developed depended on (a) the presence and concentration of mannitol, (b) the duration of urinary stasis, and (c) the plasma concentration of HCO3-. 3. If a solution containing 15% (w/v) mannitol was infused I.V., the HCO3- concentration in free flow urine was lower than in plasma, and it fell further during arrest of flow in the entire column of trapped fluid. If less mannitol was infused, or none at all, interruption of urine flow led to a striking increase of HCO3- concentration in the distal portion of the occluded column, and to a fall in the fluid arrested in the proximal segments. 4. It was demonstrated that the HCO3- concentration attained after 2½, 6, or 15 min of urinary stasis at any point in the trapped fluid column was due to the combined effects of water reabsorption and HCO3- reabsorption which proceeded independently, and with a different time course. 5. If mannitol was administered the lowest urinary HCO3- concentration in the series moved progressively to a more distal location with increasing duration of urinary stasis. When HCO3- concentration peaks were present in distal fluid they were conspicuous only after short interruptions of urine flow; during extended stop-flow periods they became attenuated, or disappeared. If no mannitol was administered this did not occur. 6. Provided the plasma level of HCO3- was sufficiently elevated, mannitol (15%, w

  3. 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.

  4. FGF23 promotes renal calcium reabsorption through the TRPV5 channel

    PubMed Central

    Andrukhova, Olena; Smorodchenko, Alina; Egerbacher, Monika; Streicher, Carmen; Zeitz, Ute; Goetz, Regina; Shalhoub, Victoria; Mohammadi, Moosa; Pohl, Elena E; Lanske, Beate; Erben, Reinhold G

    2014-01-01

    αKlotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, αKlotho also functions as the obligatory co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in αKlotho knockout mice. We further demonstrate that αKlotho neither co-localizes with TRPV5 nor is regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor-αKlotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not αKlotho, as a calcium-conserving hormone in the kidney. PMID:24434184

  5. 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

  6. 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.

  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. PMID:27282297

  8. Mode of action of parathyroid hormone and cyclic adenosine 3′,5′-monophosphate on renal tubular phosphate reabsorption in the dog

    PubMed Central

    Agus, Zalman S.; Puschett, Jules B.; Senesky, Dorothy; Goldberg, Martin

    1971-01-01

    To evaluate the effects of parathyroid hormone and cyclic adenosine monophosphate on proximal tubular sodium and phosphate reabsorption, micropuncture studies were performed on dogs that received a highly purified preparation of parathyroid hormone (PTH), dibutyryl cyclic 3′,5′-adenosine monophosphate (cyclic AMP), 5′-AMP, and saline. PTH resulted in a 30-40% inhibition of sodium and phosphate reabsorption in the proximal tubule unassociated with a rise in either total kidney or single nephron glomerular filtration rate (GFR). The bulk of the phosphate rejected proximally was excreted in the final urine while sodium excretion rose minimally despite the marked proximal inhibition, consistent with the presence of reabsorptive sites in the distal nephron for sodium but not phosphate. The infusion of dibutyryl cyclic AMP either systemically or directly into the renal artery inhibited proximal sodium and phosphate reabsorption in the absence of changes in either total kidney or single nephron GFR, resembling the effects of PTH quantitatively and qualitatively. In contrast, another adenine nucleotide, 5′-AMP, did not inhibit the reabsorption of either sodium or phosphate. These observations support the thesis that renal effects of PTH are mediated via stimulation of renal cortical adenyl cyclase. The infusion of a moderate saline load, 25 ml/kg, also produced a similar inhibition of proximal tubular fractional sodium and phosphate reabsorption with a marked phosphaturia but only minimal natriuresis. Thus, changes in sodium and phosphate reabsorption occur in parallel in the proximal tubule when sodium reabsorption is inhibited either with volume expansion or with administration of “specific” phosphaturic agents such as PTH or cyclic AMP. These data are consistent with the thesis that phosphate reabsorption is dependent upon proximal tubular sodium reabsorption wherein the phosphaturic effect of PTH might be the result of a primary inhibition of proximal

  9. 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

  10. 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

  11. 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…

  12. Renal bicarbonate reabsorption in the rat. I. Effects of hypokalemia and carbonic anhydrase.

    PubMed Central

    Capasso, G; Kinne, R; Malnic, G; Giebisch, G

    1986-01-01

    Free-flow micropuncture studies were carried out on superficial rat proximal and distal tubules to assess the participation of different nephron segments in bicarbonate transport. Particular emphasis was placed on the role of the distal tubule, and micro-calorimetric methods used to quantitate bicarbonate reabsorption. Experiments were carried out in control conditions, during dietary potassium withdrawal, and after acute intravenous infusions of carbonic anhydrase. We observed highly significant net bicarbonate reabsorption in normal acid-base conditions as evidenced by the maintenance of significant bicarbonate concentration gradients in the presence of vigorous fluid absorption. Distal bicarbonate reabsorption persisted in hypokalemic alkalosis and even steeper transepithelial concentration gradients of bicarbonate were maintained. Enhancement of net bicarbonate reabsorption followed the acute intravenous administration of carbonic anhydrase but was limited to the nephron segments between the late proximal and early distal tubule. The latter observation is consistent with a disequilibrium pH along the proximal straight tubule (S3 segment), the thick ascending limb of Henle, and/or the early distal tubule. PMID:3097074

  13. Prostaglandin E2 stimulates sodium reabsorption in MDCK C7 cells, a renal collecting duct principal cell model.

    PubMed

    Wegmann, M; Nüsing, R M

    2003-11-01

    We examined the direct epithelial effects of the major product of arachidonic acid metabolism in the kidney, prostaglandin E(2) (PGE(2)), on ion transport and signal transduction in the hormone-sensitive Madin-Darby canine kidney (MDCK) C7 subclone as a model of renal collecting duct principal cells. MDCK C7 cells were grown on microporous permeable filter supports and mounted in Ussing-type chambers. Reverse transcriptase (RT)-PCR and sequencing were used to determine E-prostanoid (EP) receptor expression. Basolateral and, about 14-fold less potent, apical addition of PGE(2) increased short-circuit current (I(sc)) in a concentration-dependent manner. This ion transport was biphasic with a rapid peak not detectable under chloride-free conditions. The remaining, stably elevated current was unaffected by furosemide, hydrochlorothiazide, ethylisopropanol amiloride, and 5-nitro-2-(3-phenyl-propyl-amino)benzoic acid (NPPB). In contrast, apical amiloride (10 microM) significantly decreased I(sc), indicating sodium reabsorption. The effect of PGE(2) was attenuated in the presence of vasopressin. Agonists acting by cAMP elevation like dibutyryl-cAMP and theophylline also induced an amiloride-sensitive ion transport with similar kinetics as PGE(2). Moreover, PGE(2) rapidly increased intracellular cAMP levels. RT-PCR demonstrated mRNA expression of the epithelial sodium channel (ENaC), and of the EP2 receptor in MDCK C7 cells. Accordingly, EP2 receptor agonist butaprost mimicked PGE(2) epithelial action. In conclusion, PGE(2) induces amiloride-sensitive sodium reabsorption in MDCK C7 monolayers. This ion transport is most likely mediated by EP2 receptor activation leading to increased intracellular cAMP levels. Therefore, PGE(2) might also contribute to Na(+) reabsorption in the mammalian collecting duct. PMID:14580365

  14. 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

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

    PubMed

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

    2016-07-26

    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

  16. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

    PubMed Central

    Boone, Michelle

    2008-01-01

    To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease. PMID:18431594

  17. Ways of calcium reabsorption in the kidney.

    PubMed

    Moor, Matthias B; Bonny, Olivier

    2016-06-01

    The role of the kidney in calcium homeostasis has been reshaped from a classic view in which the kidney was regulated by systemic calcitropic hormones such as vitamin D3 or parathyroid hormone to an organ actively taking part in the regulation of calcium handling. With the identification of the intrinsic renal calcium-sensing receptor feedback system, the regulation of paracellular calcium transport involving claudins, and new paracrine regulators such as klotho, the kidney has emerged as a crucial modulator not only of calciuria but also of calcium homeostasis. This review summarizes recent molecular and endocrine contributors to renal calcium handling and highlights the tight link between calcium and sodium reabsorption in the kidney. PMID:27009338

  18. 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.

  19. Renal cell carcinoma: links and risks

    PubMed Central

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  20. Renal cell carcinoma: links and risks.

    PubMed

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  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

    2016-01-01

    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

  3. Lack of association of variants of the renal salt reabsorption-related genes SLC12A3 and ClC-Kb and hypertension in Mongolian and Han populations in Inner Mongolia.

    PubMed

    Chang, P Y; Zhang, X G; Su, X L

    2011-01-01

    Abnormalities in renal sodium chloride and water reabsorption play important roles in the development of hypertension. Mutations in the genes involved in renal sodium chloride reabsorption can affect blood pressure. Recently, the R904Q variant of the sodium/chloride transporters, member 3 (SLC12A3) gene and the T481S variant of the chloride channel Kb (ClC-Kb) gene were found to be implicated in essential hypertension. We investigated a possible role of the SLC12A3 and ClC-Kb genes in the prevalence of essential hypertension in the Mongolian and Han ethnic groups. The study population comprised 308 unrelated Mongolians with essential hypertension, 271 Mongolian normotensives, 285 unrelated Han with essential hypertension, and 194 Han normotensives living in Inner Mongolia. The presence of the SLC12A3 R904Q and ClC-Kb-T481S polymorphisms was determined using TaqMan PCR. The risk factors for hypertension were age, body mass index, alcohol consumption, total plasma cholesterol, and low-density lipoprotein cholesterol. The genotype and allele frequencies of SLC12A3 R904Q and ClC-Kb-T481S were not significantly different between hypertensive patients and controls in the Mongolian (SLC12A3 R904Q, P = 0.471 and P = 0.494, ClC-Kb-T481S, P = 0.960 and P = 0.960, respectively) and Han (SLC12A3 R904Q, P = 0.765 and P = 0.777, ClC-Kb-T481S, P = 0.100 and P = 0.103, respectively) populations. There was no significant association between the SLC12A3 R904Q variant and the ClC-Kb-T481S variant and essential hypertension in either ethnic group. PMID:21644212

  4. Deletion of the angiotensin II type 1 receptor–associated protein enhances renal sodium reabsorption and exacerbates angiotensin II–mediated hypertension

    PubMed Central

    Ohsawa, Masato; Tamura, Kouichi; Wakui, Hiromichi; Maeda, Akinobu; Dejima, Toru; Kanaoka, Tomohiko; Azushima, Kengo; Uneda, Kazushi; Tsurumi-Ikeya, Yuko; Kobayashi, Ryu; Matsuda, Miyuki; Uchida, Shinichi; Toya, Yoshiyuki; Kobori, Hiroyuki; Nishiyama, Akira; Yamashita, Akio; Ishikawa, Yoshihiro; Umemura, Satoshi

    2014-01-01

    Angiotensin II type 1 receptor (AT1R)–associated protein (ATRAP) promotes AT1R internalization along with suppression of pathological activation of tissue AT1R signaling. However, the functional significance of ATRAP in renal sodium handling and blood pressure regulation under pathological stimuli is not fully resolved. Here we show the blood pressure of mice with a gene-targeted disruption of ATRAP was comparable to that of wild-type mice at baseline. However, in ATRAP-knockout mice, angiotensin II–induced hypertension was exacerbated and the extent of positive sodium balance was increased by angiotensin II. Renal expression of the sodium-proton antiporter 3, a major sodium transporter in the proximal tubules, urinary pH, renal angiotensinogen production, and angiotensin II content was unaffected. Stimulation of the renal expression and activity of the epithelial sodium channel (ENaC), a major sodium transporter in the distal tubules, was significantly enhanced by chronic angiotensin II infusion. The circulating and urinary aldosterone levels were comparable. The blood pressure response and renal ENaC expression by aldosterone were not affected. Thus, ATRAP deficiency exacerbated angiotensin II–mediated hypertension by pathological activation of renal tubular AT1R by angiotensin II. This directly stimulates ENaC in the distal tubules and enhances sodium retention in an aldosterone-independent manner. PMID:24694992

  5. Accelerated reabsorption in the proximal tubule produced by volume depletion

    PubMed Central

    Weiner, Michael W.; Weinman, Edward J.; Kashgarian, Michael; Hayslett, John P.

    1971-01-01

    The renal response to chronic depletion of extracellular volume was examined using the techniques of micropuncture. Depletion of salt and water was produced by administration of furosemide to rats maintained on a sodium-free diet. There was a marked fall in body weight, plasma volume, and glomerular filtration rate. The intrinsic reabsorptive capacity of the proximal tubule, measured by the split-droplet technique, was greatly enhanced. The acceleration of proximal fluid reabsorption could not be accounted for by changes in filtration rate, tubular geometry, or aldosterone secretion. The half-time of droplet reabsorption in the distal tubule was not altered by sodium depletion. An increase in the reabsorption of fluid in the proximal tubule, as demonstrated directly in the present experiments, provides an explanation for a variety of clinical phenomena associated with volume depletion. Images PMID:5090054

  6. Renal consequences of obesity.

    PubMed

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  7. Cubilin and Amnionless Mediate Protein Reabsorption in Drosophila Nephrocytes

    PubMed Central

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

    2013-01-01

    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. PMID:23264686

  8. SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule

    PubMed Central

    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. PMID:20616166

  9. Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

    PubMed

    Welch, W J

    2015-01-01

    Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule. PMID:25345761

  10. 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

  11. 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. PMID:24402096

  12. Effects of glucose on water and sodium reabsorption in the proximal convoluted tubule of rat kidney.

    PubMed Central

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

    1978-01-01

    1. The effects of glucose on sodium and water reabsorption by rat renal proximal tubules was investigated by in situ microperfusion of segments of proximal tubules with solutions containing glucose or no glucose, with and without phlorizin. 2. Absence of glucose did not significantly alter net water flux. Sodium flux was reduced by about 10% but this was not statistically significant. 3. In the absence of glucose in the perfusion fluid net secretion of glucose occurred. 4. Phlorizin reduced either net reabsorption or net secretion of glucose; and net water flux. 5. The data suggest that in later parts of the proximal convoluted tubule some sodium may be co-transported with glucose, but that this represents only a small fraction of the total sodium reabsorption. 6. It is suggested that the glucose carrier is reversible and in appropriate circumstances could cause glucose secretion. 7. Although phlorizin alters net water flux the underlying mechanisms are not clear. 8. The calculated osmolality of the reabsorbate was significantly greater than the perfusate osmolality and greater than plasma osmolality although this was not quite significant statistically. PMID:633143

  13. Fluid reabsorption in Henle's loop and urinary excretion of sodium and water in normal rats and rats with chronic hypertension

    PubMed Central

    Stumpe, Klaus O.; Lowitz, Hans D.; Ochwadt, Bruno

    1970-01-01

    The function of the short loops of Henle was investigated by micropuncture technique in normal rats, in rats with spontaneous hypertension, and in the untouched kidney of rats with experimental renal hypertension. All animals received a standard infusion of 1.2 ml of isotonic saline per hr. With increasing arterial blood pressure (range from 90 to 220 mm Hg), a continuous decrease in transit time of Lissamine green through Henle's loop from 32 to 10 sec was observed. Fractional water reabsorption along the loop declined progressively from 26 to 10%, and fractional sodium reabsorption decreased from 40 to 36% of the filtered load. The fluid volume in Henle's loop calculated from transit time and mean flow rate also decreased with increasing blood pressure. There was no change in superficial single nephron filtration rate but there was a slight increase in total glomerular filtration rate (GFR). Sodium and water reabsorption in the proximal tubule remained unchanged. Urine flow rate, sodium excretion, osmolar clearance, and negative free water clearance increased with increasing blood pressure. The osmolal urine to plasma (U/P) ratio declined but did not fall below a value of 1.5. It is concluded that the increase in sodium and water excretion with chronic elevation of arterial blood pressure is caused by a decrease of sodium and water reabsorption along the loop of Henle, presumably as a consequence of increased medullary blood pressure. PMID:5422022

  14. 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

  15. Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients.

    PubMed

    Perez-Ruiz, Fernando; Aniel-Quiroga, Maria Angeles; Herrero-Beites, Ana María; Chinchilla, Sandra Pamela; Erauskin, Gorka Garcia; Merriman, Toni

    2015-09-01

    Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension. PMID:25763991

  16. Fabrication of Collagen Gel Hollow Fibers by Covalent Cross-Linking for Construction of Bioengineering Renal Tubules.

    PubMed

    Shen, Chong; Zhang, Guoliang; Wang, Qichen; Meng, Qin

    2015-09-01

    Collagen, the most used natural biomacromolecule, has been extensively utilized to make scaffolds for cell cultures in tissue engineering, but has never been fabricated into the configuration of a hollow fiber (HF) for cell culture due to its poor mechanical properties. In this study, renal tubular cell-laden collagen hollow fiber (Col HF) was fabricated by dissolving sacrificial Ca-alginate cores from collagen shells strengthened by carbodiimide cross-linking. The inner/outer diameters of the Col HF were precisely controlled by the flow rates of core alginate/shell collagen solution in the microfluidic device. As found, the renal tubular cells self-assembled into renal tubules with diameters of 50-200 μm post to the culture in Col HF for 10 days. According to the 3D reconstructed confocal images or HE staining, the renal cells appeared as a tight tubular monolayer on the Col HF inner surface, sustaining more 3D cell morphology than the cell layer on the 2D flat collagen gel surface. Moreover, compared with the cultures in either a Transwell or polymer HF membrane, the renal tubules in Col HF exhibited at least 1-fold higher activity on brush border enzymes of alkaline phosphatase and γ-glutamyltransferase, consistent with their gene expressions. The enhancement occurred similarly on multidrug resistance protein 2 and glucose uptake. Such bioengineered renal tubules in Col HF will present great potential as alternatives to synthetic HF in both clinical use and pharmaceutical investigation. PMID:26280545

  17. Proximal HCO3- reabsorption and the determinants of tubular and capillary PCO2 in the rat.

    PubMed

    Maddox, D A; Atherton, L J; Deen, W M; Gennari, F J

    1984-07-01

    Studies were carried out in Munich-Wistar rats to define the CO2 partial pressure (PCO2) profile in the surface tubules and capillaries of the kidney and to relate these measurements to proximal tubular HCO3- reabsorption, renal blood flow, and O2 consumption. In euvolemic rats, PCO2 in Bowman's space (BS) was 12.5 mmHg higher than in arterial blood, indicating CO2 addition to the arterial tree as it traverses the cortex. PCO2 further rose by 3.9 mmHg between the efferent arteriole (EA) and the peritubular capillaries (PC) (P less than 0.01) and by 4.9 mmHg between BS and the early proximal tubule (EP) (P less than 0.01). In studies with paired measurements, PCO2 in EP was 1.8 mmHg higher than in the adjacent PC (P less than 0.05). HCO3- reabsorption in EP (first 0.4-1.25 mm) was 579 pmol X min-1 X mm-1 (34.3 +/- 4.6% of the filtered load). By use of a model of facilitated diffusion of CO2 across the cell, the trans-epithelial PCO2 gradient in EP can be accounted for by the CO2 generated from HCO3- reabsorption, assuming an intracellular pH of 7.3. In the vascular compartment, roughly half the rise in PCO2 between the afferent arteriole (estimated to equal BS PCO2) and PC can be accounted for by metabolic CO2 production and half by titration of blood buffers by reabsorbed HCO3-. PMID:6430105

  18. 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. PMID:26759048

  19. Inflammation and hypoxia linked to renal injury by CCAAT/enhancer-binding protein δ.

    PubMed

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Eto, Nobuaki; Nangaku, Masaomi

    2015-08-01

    Tubulointerstitial hypoxia plays a critical role in the pathogenesis of kidney injury, and hypoxia-inducible factor (HIF)-1 is a master regulator of cellular adaptation to hypoxia. Aside from oxygen molecules, factors that modify HIF-1 expression and functional operation remain obscure. Therefore, we sought to identify novel HIF-1-regulating genes in kidney. A short-hairpin RNA library consisting of 150 hypoxia-inducible genes was derived from a microarray analysis of the rat renal artery stenosis model screened for the effect on HIF-1 response. We report that CCAAT/enhancer-binding protein δ (CEBPD), a transcription factor and inflammatory response gene, is a novel HIF-1 regulator in kidney. CEBPD was induced in the nuclei of tubular epithelial cells in both acute and chronic hypoxic kidneys. In turn, CEBPD induction augmented HIF-1α expression and its transcriptional activity. Mechanistically, CEBPD directly bound to the HIF-1α promoter and enhanced its transcription. Notably, CEBPD was rapidly induced by inflammatory cytokines, such as IL-1β in a nuclear factor-κB-dependent manner, which not only increased HIF-1α expression during hypoxia, but was also indispensable for the non-hypoxic induction of HIF-1α. Thus our study provides novel insight into HIF-1 regulation in tubular epithelial cells and offers a potential hypoxia and inflammation link relevant in both acute and chronic kidney diseases. PMID:25692954

  20. The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

    PubMed

    Vree, T B; Guelen, P J; Jongman-Nix, B; Walenkamp, G H

    1981-07-18

    The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin. PMID:6166414

  1. 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

  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. PMID:23973373

  3. Photofission of [sup 182]W following reabsorption of photopions

    SciTech Connect

    Arruda-Neto, J.D.T.; Saito, T.; Sugawara, M.; Tamae, T.; Miyase, H.; Abe, K.; Konno, O.; Oikawa, M. ); Deppman, A.; Simionatto, S.; Macedo, E.M.L.; Bhandari, B.S. )

    1995-02-01

    The electrofission cross section of [sup 182]W was measured in the range 80--180 MeV. A pronounced inflexion, corresponding to a sharp structure in the ([gamma],[ital f]) curve, shows up around 140 MeV. A photofission model, based on a photopion-deuteron reabsorption process, was worked out to explain this finding. Good agreement between calculation and experimental data was achieved.

  4. 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

  5. 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. PMID:26982719

  6. [Renal physiology].

    PubMed

    Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

    2012-03-01

    The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body. PMID:22157516

  7. Quantitative Structure-Pharmacokinetic Relationships for the Prediction of Renal Clearance in Humans

    PubMed Central

    Dave, Rutwij A.

    2015-01-01

    Renal clearance (CLR), a major route of elimination for many drugs and drug metabolites, represents the net result of glomerular filtration, active secretion and reabsorption, and passive reabsorption. The aim of this study was to develop quantitative structure-pharmacokinetic relationships (QSPKR) to predict CLR of drugs or drug-like compounds in humans. Human CLR data for 382 compounds were obtained from the literature. Step-wise multiple linear regression was used to construct QSPKR models for training sets and their predictive performance was evaluated using internal validation (leave-one-out method). All qualified models were validated externally using test sets. QSPKR models were also constructed for compounds in accordance with their 1) net elimination pathways (net secretion, extensive net secretion, net reabsorption, and extensive net reabsorption), 2) net elimination clearances (net secretion clearance, CLSEC; or net reabsorption clearance, CLREAB), 3) ion status, and 4) substrate/inhibitor specificity for renal transporters. We were able to predict 1) CLREAB (Q2 = 0.77) of all compounds undergoing net reabsorption; 2) CLREAB (Q2 = 0.81) of all compounds undergoing extensive net reabsorption; and 3) CLR for substrates and/or inhibitors of OAT1/3 (Q2 = 0.81), OCT2 (Q2 = 0.85), MRP2/4 (Q2 = 0.78), P-gp (Q2 = 0.71), and MATE1/2K (Q2 = 0.81). Moreover, compounds undergoing net reabsorption/extensive net reabsorption predominantly belonged to Biopharmaceutics Drug Disposition Classification System classes 1 and 2. In conclusion, constructed parsimonious QSPKR models can be used to predict CLR of compounds that 1) undergo net reabsorption/extensive net reabsorption and 2) are substrates and/or inhibitors of human renal transporters. PMID:25352657

  8. Partial Characterization of the Molecular Nature of Collagen-Linked Fluorescence: Role of Diabetes and End-Stage Renal Disease

    PubMed Central

    Sell, David R.; Nemet, Ina; Monnier, Vincent M.

    2009-01-01

    Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes and ESRD. It has a molecular weight of 623.2 Da, a UV maximum at 348 nm, and involves a lysine residue in an aromatic ring. LW-1 could not be synthesized using traditional glycation chemistry suggesting a complex mechanism of formation, perhaps related to hypoxia since elevated levels were also found in nondiabetic individuals with chronic lung disease. PMID:19879855

  9. 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. PMID:26235579

  10. Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption▿

    PubMed Central

    Chu, Jessica Y. S.; Chung, Samuel C. K.; Lam, Amy K. M.; Tam, Sidney; Chung, Sookja K.; Chow, Billy K. C.

    2007-01-01

    Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp). Studies using Vp-deficient Brattleboro rats, however, indicated the existence of substantial Vp-independent mechanisms for membrane insertion, as well as transcriptional regulation, of this water channel. The Vp-independent mechanism(s) is clinically relevant to patients with X-linked nephrogenic diabetes insipidus (NDI) by therapeutically bypassing the dysfunctional Vp receptor. On the basis of studies with secretin receptor-null (SCTR−/−) mice, we report here for the first time that mutation of the SCTR gene could lead to mild polydipsia and polyuria. Additionally, SCTR−/− mice were shown to have reduced renal expression of AQP2 and AQP4, as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption process in these animals. By using SCTR−/− mice as controls and comparing them with wild-type animals, we performed both in vivo and in vitro studies that demonstrated a role for secretin in stimulating (i) AQP2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules and (ii) expression of this water channel under hyperosmotic conditions. The present study therefore provides information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating NDI patients. PMID:17283064

  11. Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets.

    PubMed Central

    Tenenhouse, H S; Yip, A; Jones, G

    1988-01-01

    The hypophosphatemic (Hyp) mouse, a murine homologue of human X-linked hypophosphatemic rickets, is characterized by renal defects in brush border membrane phosphate transport and vitamin D3 metabolism. The present study was undertaken to examine whether elevated renal 25-hydroxyvitamin D3-24-hydroxylase activity in Hyp mice is associated with increased degradation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by side chain oxidation. Metabolites of 1,25(OH)2D3 were separated by HPLC on Zorbax SIL and identified by comparison with standards authenticated by mass spectrometry. Production of 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, and 24-oxo-1,23,25-trihydroxyvitamin D3 was twofold greater in mitochondria from mutant Hyp/Y mice than from normal +/Y littermates. Enzyme activities, estimated by the sum of the three products synthesized per milligram mitochondrial protein under initial rate conditions, were used to estimate kinetic parameters. The apparent Vmax was significantly greater for mitochondria from Hyp/Y mice than from +/Y mice (0.607 +/- 0.064 vs. 0.290 +/- 0.011 pmol/mg per protein per min, mean +/- SEM, P less than 0.001), whereas the apparent Michaelis-Menten constant (Km) was similar in both genotypes (23 +/- 2 vs. 17 +/- 5 nM). The Km for 1,25(OH)2D3 was approximately 10-fold lower than that for 25-hydroxyvitamin D3 [25(OH)D3], indicating that 1,25(OH)2D3 is perhaps the preferred substrate under physiological conditions. In both genotypes, apparent Vmax for 25(OH)D3 was fourfold greater than that for 1,25(OH)2D3, suggesting that side chain oxidation of 25(OH)D3 may operate at pharmacological concentrations of substrate. The present results demonstrate that Hyp mice exhibit increased renal catabolism of 1,25(OH)2D3 and suggest that elevated degradation of vitamin D3 hormone may contribute significantly to the clinical phenotype in this disorder. PMID:3339128

  12. Familial renal glycosuria and modifications of glucose renal excretion.

    PubMed

    Prié, D

    2014-12-01

    Under physiological conditions, the kidneys contribute to glucose homoeostasis by producing glucose by gluconeogenesis and preventing glucose loss in urine. The glucose filtered by the glomeruli is completely reabsorbed in the renal proximal tubule. Renal gluconeogenesis produces 25% of the circulating glucose in the postabsorptive state, while the amount of glucose reabsorbed by the kidneys largely exceeds the quantity synthesized by kidney gluconeogenesis. Sodium-glucose cotransporter type 2 (SGLT-2) and glucose transporter 2 (GLUT2) carry out more than 90% of renal glucose uptake. In diabetes, both gluconeogenesis and renal glucose reabsorption are increased. The augmentation of glucose uptake in diabetes is due to the overexpression of renal glucose transporters SGLT-2 and GLUT2 in response to the increase in expression of transcription activator hepatic nuclear factor 1-alpha (HNF1α). The rise in glucose uptake contributes to hyperglycaemia and induces glomerular hyperfiltration by increasing sodium and water reabsorption in the proximal tubule that, in turn, modifies urine flux at the macula densa. SGLT-2 inhibitors improve glycaemic control and prevent renal hyperfiltration in diabetes. Loss of SGLT-2 transporter function is a benign state characterized by glycosuria. In contrast, mutations of other glucose transporters expressed in the kidney are responsible for severe disorders. PMID:25554066

  13. Renal mu opioid receptor mechanisms in regulation of renal function in rats.

    PubMed

    Kapusta, D R; Jones, S Y; DiBona, G F

    1991-07-01

    Studies were performed in pentobarbital anesthetized Sprague-Dawley rats to determine whether mu opioid receptor agonists produce changes in renal function via intrarenal mechanisms. Left renal artery infusion of isotonic saline vehicle or the selective mu opioid receptor agonist, dermorphin (0.5 nmol/kg/min), did not alter mean arterial pressure or heart rate. In contrast, left renal artery dermorphin administration produced a significant decrease in left kidney urinary flow rate and sodium excretion without altering glomerular filtration rate or effective renal plasma flow; function of the right kidney was unaffected. Pretreatment of the left kidney with the opioid receptor antagonist naloxone, 50 micrograms/kg into left renal artery, prevented changes in urinary flow rate and sodium excretion induced by subsequent left renal artery dermorphin administration. Prior bilateral renal denervation abolished the antidiuretic and antinatriuretic responses to left renal artery dermorphin administration. These results suggest that mu opioid receptor agonists participate in the process of renal tubular sodium and water reabsorption via an intrarenal action that is dependent on an interaction with renal sympathetic nerves. This may occur via an action of mu opioid receptor agonists to facilitate the nerve terminal release and/or the direct tubular action of norepinephrine to affect renal tubular sodium and water reabsorption. PMID:1677034

  14. [Detoxication effect of water-soluble imprinted cross-linked chitosan on depleted uranium induced toxicity to renal cells].

    PubMed

    Zhang, Xiao-fei; Li, Chao; Zhao, Chang-qi; Liu, Li-hong

    2011-05-01

    To investigate whether a series of water-soluble cross-linked chitosan derivates synthesized in the guide of imprinting technology could be used as a uranium chelating agent to protect cells exposed to depleted uranium (DU), the imprinted chitosan derivates with high UO2(2+) chelating ability were screened, and cell model of human renal proximal tubule epithelium cells (HK-2) exposed to DU (500 micromol.L-1) was built, chitosan derivates (400 mg.L-1 ) was added to test group and diethylenetriaminepentaacetic acid (DTPA, 50 mg.L-1) was added to positive control group. The results showed that three Cu2+ imprinted chitosan derivates had higher uranium chelating ability (>49 microg.mg-1) than chitosan and non-imprinted chitosan derivates. Compared to the cells exposed to DU only, survival of cells in group added chitosan derivates rose up significantly (increased from 57.3% to 88.7%, and DTPA to 72.6%), and DU intracellular accumulation decreased, membrane damage and DNA damage also eased. Among the imprinted chitosan derivates, Cu2+ imprinted penta dialdehyde cross-linked carboxymethyl chitosan (Cu-P-CMC) was the best, and better than DTPA. From ultrastructure observation, the DU precipitates of test group added Cu-P-CMC were most grouped in a big hairy clusters in a string together outside cells. It is possible that the DU-chitosan derivates precipitates are too big to enter into cells, and from this way, the DU uptake by cells decreased so as to detoxication. PMID:21800537

  15. Leptin in end stage renal disease (ESRD): a link between fat mass, bone and the cardiovascular system.

    PubMed

    Mallamaci, F; Tripepi, G; Zoccali, C

    2005-01-01

    Adipose tissue is now considered an important system operating strictly in concert with other systems. The adipocyte is the main producer of two pleiotropic compounds, leptin and adiponectin, modulating inflammation and having multiple effects in disparate organs including the cardiovascular and the central nervous system. Leptin has disparate influences on various physiologic and organ systems including glucose homeostasis, hematopoiesis and the reproductive and cardiovascular systems and is a crucial hormone for the regulation of food intake and body weight. Peripherally, leptin modulates insulin sensitivity and high leptin triggers insulin resistance and vice versa. Obesity, a situation where circulating leptin attains very high levels is accompanied by increased bone mass, a phenomenon which may depend on direct stimulation of osteoblasts by leptin. However in animal models the stimulating effect of leptin on the osteoblast is counterbalanced by a strong inhibitor effect on bone formation in the central nervous system. Two recent studies reported an inverse link between leptin, bone mass and PTH in dialysis patients suggesting that leptin may be implicated in low bone turnover in these patients, likely by a mechanism involving the central nervous system. Leptin induces vascular calcifications in vitro. In uremic man leptin is unrelated to valvular calcifications but predicts incident cardiovascular events in overweight and obese dialysis patients. Leptin seems to be a relevant player in the emerging connection between bone and cardiovascular alterations in patients with end stage renal disease. PMID:16245256

  16. 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

  17. Genetics Home Reference: renal coloboma syndrome

    MedlinePlus

    ... 1 link) The Kidney and Urology Foundation of America GeneReviews (1 link) Renal Coloboma Syndrome Genetic Testing Registry (1 link) Renal coloboma syndrome Scientific articles on PubMed (1 link) PubMed OMIM (1 ...

  18. 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.

  19. Inappropriate tall stature and renal ectopy in a male patient with X-linked congenital adrenal hypoplasia due to a novel missense mutation in the DAX-1 gene.

    PubMed

    Franzese, Adriana; Brunetti-Pierri, Nicola; Spagnuolo, Maria Immacolata; Spadaro, Raffaella; Giugliano, Michela; Mukai, Tokuo; Valerio, Giuliana

    2005-05-15

    Mutations in DAX-1 gene cause congenital adrenal hypoplasia (AHC). We present a male patient affected by X-linked adrenal hypoplasia congenita due to a novel DAX-1 missense mutation. The mutation V287G affects the C-terminal end of the DAX-1 protein which plays an important role in functioning of the receptor. In addition, our patient presented an inappropriate tall stature and renal ectopy, which have not been described in AHC so far. PMID:15800903

  20. ADH-PGE2 interactions in cortical collecting tubule. II. inhibition of Ca and P reabsorption.

    PubMed

    Holt, W F; Lechene, C

    1981-10-01

    In the absence of ADH, microperfused cortical collecting tubules of rabbits reabsorb calcium and phosphorus. Antidiuretic hormone (ADH) (200 microunits/ml Pitressin or synthetic arginine vasopressin) inhibits the reabsorption and may promote the secretion of calcium and phosphorus. At 5 min after incubation with ADH, there was a transitory increase in the potential difference and the reabsorption of sodium. The fluxes of calcium and phosphorus, however, showed no significant change from the control values. At 30-50 min after treatment with ADH, the reabsorption of calcium and phosphorus was inhibited and in some tubules calcium and phosphorus were secreted. The removal of vasopressin from the bath or the addition of 10(-5) M meclofenamate in vitro prevented ADH from inhibiting the reabsorption of calcium and phosphorus. Treatment of tubules with 10(-5) M prostaglandin E2 (PGE2) subsequent to incubation in a medium containing ADH and meclofenamate inhibited the reabsorption or even promoted the secretin of calcium and phosphorus, as did the prolonged incubation with ADH alone. We conclude that cortical collecting tubules reabsorb calcium and phosphorus in the absence of vasopressin and that ADH inhibits calcium and phosphorus reabsorption. Endogenous synthesis of PGE2 may mediate the inhibitory action of ADH, since meclofenamate (an inhibitor of the synthesis of prostaglandins) opposes and exogenous PGE2 mimics ADH. PMID:6947697

  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. Assessment of the place of tubular reabsorption of phosphorus in the diagnosis of osteopenia of prematurity

    PubMed Central

    Acar, Duygu Besnili; Kavuncuoğlu, Sultan; Çetinkaya, Merih; Petmezci, Ercüment; Dursun, Mesut; Korkmaz, Orhan; Altuncu, Emel Kayrak

    2015-01-01

    Aim: In this study, we aimed to investigate the utility of tubular reabsorption of phosphorus in the diagnosis of osteopenia of prematurity in addition to biochemical markers. Materials and Method: Premature babies with a gestational age of ≤32 weeks and/or a birth weight of ≤1 500 g who were hospitalized in the neonatal intensive care unit between June 2009 and March 2011 were included in the study. These babies were evaluated at the 40th gestational week and serum calcium, phosphorus, alkaline phosphatase, urea, creatinine, urinary calcium and phosphorus levels were measured and tubular reabsorption of phosphorus was determined. The subjects who had bone graphy findings and/or an alkaline phosphatase level of >400IU/L and a phosphorus value of <3.5 mg/dL were considered osteopenic. The levels of tubular reabsorption of phosphorus of the osteopenic patients were compared with the ones of the non-osteopenic patients. The study was initiated after obtaining ethics committee approval (date: 04.29.2009/213). Results: During the study period, a total of 698 premature babies were hospitalized in our neonatology unit. A diagnosis of osteopenia of prematurity was made in 24 of 190 subjects who met the study criteria. The level of tubular reabsorption of phosphorus was compared with the serum calcium, phosphorus and alkaline phosphatase levels measured at the 40th gestational week and alkaline phosphatase was found to be significantly increased in the group with a high tubular reabsorption of phosphorus (≥%95). When the subjects with a phosphorus level of <3.5 mg/dL and an alkaline phosphatase level of >499 IU were compared with the newborns who were found to have a tubular reabsorption of phosphorus of ≥%95 for the objective of evaluating the specificity and sensitivity of tubular reabsorption of phosphorus, the sensitivity, specificity, positive predictive value and negative predictive value of tubular reabsorption of phosphorus in the diagnosis of osteopenia

  3. Role of basolateral cell membranes in organic solute reabsorption in rabbit kidneys.

    PubMed

    Foulkes, E C

    1987-06-01

    The present work explores the contributions of basolateral carrier systems in tubular reabsorption of organic solutes. Reabsorption of sugars and amino acids, as previously shown, can be represented by a three-compartment linear model that predicts that 1) if basolateral transport contributes to sugar reabsorption, alpha-methylglucoside reabsorption compared with that of glucose should be characterized by a longer transepithelial transit time (TET) and a correspondingly increased cellular transport pool (S), and 2) saturation of basolateral amino acid carriers, or presence of competing amino acids or other basolateral transport inhibitors, should prolong TET of a test amino acid, and increase S above the expected value. Both predictions were fully confirmed. Heavy metal intoxication not only inhibits transport of amino acids at the brush border, but also prolongs their TET and increases the size of S for a given reabsorbed load. Basolateral extrusion of amino acids is more sensitive to metals than is uptake across the brush border. Although basolateral carriers accelerate return of reabsorbed solute to blood, their contribution to reabsorption does not seem to be mandatory. PMID:3591952

  4. 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. PMID:24987788

  5. Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats.

    PubMed

    Kapusta, D R; Jones, S Y; DiBona, G F

    1990-06-01

    The aims of the present study were to examine the effects of opioid receptor agonists and antagonists on the renal vascular (renal blood flow) and tubular (urinary sodium excretion) responses to renal nerve stimulation and norepinephrine in anesthetized spontaneously hypertensive rats (SHR). Graded frequency renal nerve stimulation (0.5-4.0 Hz) and doses of norepinephrine (10-80 ng/kg) produced frequency and dose-dependent decreases in renal blood flow. The renal vasoconstrictor responses were not altered by intravenous infusion of the opioid receptor agonists methionine enkephalin (mu and delta, 75 micrograms/kg/min) or U-50488H (kappa, 20 micrograms/kg/min) or administration of the opioid receptor antagonist naloxone (1 mg/kg i.v.). The antinatriuretic response to low frequency (less than 1.0 Hz) electrical renal nerve stimulation was prevented by naloxone but not affected by methionine enkephalin administration without changes in glomerular filtration rate or effective renal plasma flow. These studies suggest that endogenous opioid receptor mechanisms are involved in the increased renal tubular sodium reabsorption response to low frequency renal nerve stimulation but not in the renal vasoconstrictor response to either renal nerve stimulation or norepinephrine. This might occur by facilitation of the renal nerve terminal release, the direct renal tubular action, or both, of norepinephrine to influence renal tubular sodium reabsorption. PMID:2351429

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

    SciTech Connect

    Zhang, Wenxia; Dai, Dejian; Chen, Xifang; Guo, Xiaoxiao; Fan, Jiyang

    2014-03-03

    We synthesize the colloidal carbon/graphene quantum dots 1–9 nm in diameter and study their photoluminescence properties. Surprisingly, the luminescence properties of a fixed collection of colloidal carbon quantum 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 quantum dots are substantially terminated by oxygen atoms, which causes their ultra-high hydrophilicity. Our result clarifies the mystery of distinct emission colors in carbon quantum dots and indicates that photon reabsorption can strongly affect the luminescence properties of colloidal nanocrystals.

  7. Role of MHC-Linked Genes in Autoantigen Selection and Renal Disease in a Murine Model of Systemic Lupus Erythematosus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2b, the haplotype on which the knockout was derived, whereas the wild-type littermates were H2k, the H2 of MRL/lpr mice. To determine which protect...

  8. 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. PMID:27226106

  9. A simple slide-rule method for the assessment of renal tubular reaborption of phosphate in man.

    PubMed

    Walton, R J; Bijvoet, O L

    1977-12-15

    The activity of renal tubular reabsorption of phosphate in man is best expressed as the ratio of the maximum rate or reabsorption to the glomerular filtration rate (TmP/GFR). A slide-rule method based on existing data is described for the derivation of TmP/GFR from values of phosphate and creatinine concentrations in single samples of plasma and urine. This is a simple method which is suitable both for research and for clinical purposes. PMID:923101

  10. Renal P2 receptors and hypertension.

    PubMed

    Menzies, R I; Unwin, R J; Bailey, M A

    2015-01-01

    The regulation of extracellular fluid volume is a key component of blood pressure homeostasis. Long-term blood pressure is stabilized by the acute pressure natriuresis response by which changes in renal perfusion pressure evoke corresponding changes in renal sodium excretion. A wealth of experimental evidence suggests that a defect in the pressure natriuresis response contributes to the development and maintenance of hypertension. The mechanisms underlying the relationship between renal perfusion pressure and sodium excretion are incompletely understood. Increased blood flow through the vasa recta increases renal interstitial hydrostatic pressure, thereby reducing the driving force for transepithelial sodium reabsorption. Paracrine signalling also contributes to the overall natriuretic response by inhibiting tubular sodium reabsorption in several nephron segments. In this brief review, we discuss the role of purinergic signalling in the renal control of blood pressure. ATP is released from renal tubule and vascular cells in response to increased flow and can activate P2 receptor subtypes expressed in both epithelial and vascular endothelial/smooth muscle cells. In concert, these effects integrate the vascular and tubular responses to increased perfusion pressure and targeting P2 receptors, particularly P2X7, may prove beneficial for treatment of hypertension. PMID:25345692

  11. In vivo microperfusion of the ductuli efferentes testis of the rat: flow dependence of fluid reabsorption.

    PubMed

    Clulow, J; Hansen, L A; Jones, R C

    1996-07-01

    Individual ducts from the initial zone of the efferent ducts of the rat were microperfused in vivo using a double cannulation procedure, which allowed the recovery of perfused fluids for analysis and determination of the rate of fluid reabsorption from the perfused duct. The ducts were perfused at rates from 0.025 to 0.4 microliters min-1 with either Krebs-Ringer bicarbonate (KRB) solution or the native rete testis fluid (nRTF) that perfuses the ducts in situ. Reabsorption of KRB solution increased linearly with a perfusion rate of between 0.025 and 0.1 microliter min-1 (from 17.4 +/- 1.5 to 34.3 +/- 3.2 nl (10 mm duct)-1 min-1), then increased no further. Reabsorption of nRTF increased linearly between 0.025 and 0.2 microliters min-1 (from 17.7 +/- 1.5 to 61.4 +/- 13.5 nl (10 mm duct)-1 min-1) and then declined. The reabsorption rate from nRTF perfusates was significantly higher than from KRB perfusates. As a proportion of the luminal perfusate, reabsorption declined from 73.0 +/- 6.0 to 7.4 +/- 3.0% (10 mm duct)-1 for KRB solution and from 73.1 +/- 6.0 to 4.1 +/- 1.3% (10 mm duct)-1 for nRTF. There was no significant change in the concentration of either Na+ or Cl- in KRB solution or nRTF during perfusion through the efferent ducts, indicating that the reabsorption of these ions was isomolar. However, the reabsorption of K+ from nRTF occurred at a greater rate than that of water, and the initial [K+] declined from 17.2 +/- 0.4 mM in nRTF perfusates to 5.7 +/- 0.5 mM in collectates (perfusion rate, 0.1 microliter min-1) to achieve equilibrium with blood plasma (4.7 +/- 0.4 mM). The osmotic pressure of both KRB and nRTF perfusates equilibrated with blood plasma, indicating a high permeability of the epithelium to water. The results of this study provide further evidence that fluid reabsorption in the efferent ducts is isosmotic, or close to isosmotic, and have shown that, as in the homologous proximal kidney tubule, reabsorption is dependent on luminal flow rate

  12. The effect of surgery on the renal excretion of beta 2-microglobulin.

    PubMed

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  13. A novel mu-capture enzyme-linked immunosorbent assay based on recombinant proteins for sensitive and specific diagnosis of hemorrhagic fever with renal syndrome.

    PubMed Central

    Zöller, L G; Yang, S; Gött, P; Bautz, E K; Darai, G

    1993-01-01

    Hantavirus nucleocapsid protein has recently been identified as a major antigen inducing an early and long-lasting humoral immune response in patients with hemorrhagic fever with renal syndrome. A mu-capture enzyme-linked immunosorbent assay utilizing recombinant nucleocapsid proteins of Hantavirus strains Hantaan 76-118 (Hantaan serotype) and CG 18-20 (Puumala serotype) as diagnostic antigens and specific monoclonal antibodies as the detection system has been developed. Histidine-tailed recombinant proteins were expressed in Escherichia coli and purified in a single step by affinity chromatography on a nickel-chelate resin. The assay was evaluated with a panel of sera from patients with hemorrhagic fever with renal syndrome originating from various geographic regions. The overall sensitivity of the mu-capture enzyme-linked immunosorbent assay (both recombinant antigens) was 100%, and its specificity was also found to be 100%. Immunoglobulin M antibodies were detected as early as on day 3, and maximum titers were obtained between days 8 and 25 after onset of the disease. The assay was regularly found to be positive within 3 to 4 months but in some cases up to 2 years after the acute phase of the disease. Images PMID:8099085

  14. 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. PMID:9189257

  15. 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

  16. Population pharmacokinetics of nefopam in elderly, with or without renal impairment, and its link to treatment response

    PubMed Central

    Djerada, Zoubir; Fournet-Fayard, Aurélie; Gozalo, Claire; Lelarge, Chantal; Lamiable, Denis; Millart, Hervé; Malinovsky, Jean-Marc

    2014-01-01

    Aims Nefopam is a nonmorphinic central analgesic, for which no recommendation exists concerning adaptation of regimen in aged patients with or without renal impairment. The objective was to describe the pharmacology of nefopam in aged patients to obtain guidelines for practical use. Methods Elderly patients (n = 48), 65–99 years old, with severe or moderate renal impairment or with normal renal function, were recruited. Nefopam (20 mg) was administered as a 30 min infusion postoperatively. Simultaneously, a 1 min intravenous infusion of iohexol was performed, in order to calculate the glomerular filtration rate. Blood samples were drawn to determine nefopam, desmethyl-nefopam and iohexol plasma concentrations. Nefopam and desmethyl-nefopam concentrations were analysed using a nonlinear mixed-effects modelling approach with Monolix version 4.1.3. The association between pharmacokinetic parameters and treatment response was assessed using logistic regression. Results A two-compartment open model was selected to describe the pharmacokinetics of nefopam. The typical population estimates (between-subject variability) for clearance, volume of distribution, intercompartmental clearance and peripheral volume were, respectively, 17.3 l h−1 (53.2%), 114 l (121%), 80.7 l h−1 (79%) and 208 l (63.6%). Morphine requirement was related to exposure of nefopam. Tachycardia and postoperative nausea and vomiting were best associated with maximal concentration and the rate of increase in nefopam plasma concentration. Conclusions We identified the nefopam pharmacokinetic predictors for morphine requirement and side-effects, such as tachycardia and postoperative nausea and vomiting. In order to maintain morphine sparing and decrease side-effects following a single dose of nefopam (20 mg), simulations suggest an infusion time of >45 min in elderly patients with or without renal impairment. PMID:24252055

  17. 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

  18. 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

  19. 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.

  20. 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. PMID:26041448

  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. 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.

  3. Reabsorption trapping of luminecence in laser crystals: enhancement of energy storage and upconversion

    SciTech Connect

    Noginov, M.A.

    1997-06-01

    It is shown that reabsorption of luminescence in laser crystals can enhance energy storage, energy transfer, and upconversion in solid-state laser media. These effects, experimentally observed in Yb-doped and Er-doped crystals, can potentially decrease the threshold for compact cw pumped lasers. The influence of parasitic laser modes and the amplification of spontaneous emission on population inversion in reflective coated laser elements is discussed. {copyright} 1997 Optical Society of America

  4. Renal Effects of Prostaglandins and Cyclooxygenase-2 Inhibitors

    PubMed Central

    2008-01-01

    Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin (PGI2). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. Under conditions of decreased renal perfusion, the production of renal PGs serves as an important compensatory mechanism. PGI2 (and possibly PGE2) increases potassium secretion mainly by stimulating secretion of renin and activating the renin-angiotensin system, which leads to increased secretion of aldosterone. In addition, PGE2 is involved in the regulation of sodium and water reabsorption and acts as a counterregulatory factor under conditions of increased sodium reabsorption. PGE2 decreases sodium reabsorption at the thick ascending limb of the loop of Henle probably via inhibition of the Na+-K+-2Cl- cotransporter type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating ability in part through effects to upregulate NKCC2 in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct. Thus, they may be useful to treat Bartter's syndrome and nephrogenic diabetes insipidus. PMID:24459520

  5. 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. PMID:20664559

  6. Desmopressin use prior to renal transplant biopsy—does it fit?

    PubMed Central

    Anandagoda, Nelomi; Jayawardene, Satish; Macdougall, Iain C.; Shah, Sapna

    2014-01-01

    Desmopressin acetate (DDAVP), a selective agonist of type 2 vasopressin receptors, is sometimes used prior to percutaneous renal biopsy to reduce the risk of bleeding complications. DDAVP increases free water reabsorption in renal collecting ducts, potentially leading to water intoxication or dilutional hyponatraemia. We present two cases, where DDAVP was used prior to percutaneous renal transplant biopsy and was associated with severe hyponatraemia and neurological sequelae. With DDAVP being advocated in many centres prior to percutaneous renal biopsy, these cases highlight the need for increased awareness regarding side effects. In this report, we provide suggestions on strategies to minimize hyponatraemia in this context. PMID:25859381

  7. Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter.

    PubMed

    Leung, G P; Cheung, K H; Tse, C M; Wong, P Y

    2001-03-01

    The effect of nucleoside on Na+ reabsorption via Na+/nucleoside cotransporter in cultured rat epididymal epithelia was studied by short-circuit current (Isc) technique. Guanosine added apically stimulated Isc in a dose-dependent manner, with a median effective concentration (EC50) of 7 +/- 2 microM (mean +/- SEM). Removal of Na+ from the apical bathing solution or pretreatment with a nonspecific Na+/nucleoside cotransporter inhibitor, phloridzin, completely blocked the Isc response to guanosine. Moreover, the guanosine response was abolished by pretreatment of the tissue with ouabain, a Na+/K+-ATPase inhibitor, suggesting the involvement of Na+/nucleoside cotransporter on the apical side and Na+/K+-ATPase on the basolateral side in Na+ reabsorption. In contrast, the Isc response to guanosine was not affected after desensitization of purinoceptors by ATP. Addition of the Na+/K+/2Cl- symport inhibitor bumetanide to the basolateral side or the nonspecific Cl- channel blocker diphenylamine-2-carboxylate to the apical side showed no effect on the Isc response to guanosine, excluding stimulation of Cl- secretion by guanosine as the cause of the guanosine-induced Isc. The Isc response to purine nucleoside (guanosine and inosine) was much higher than that to pyrimidine nucleoside (thymidine and cytidine). Consistent with substrate specificity, results of reverse transcription-polymerase chain reaction revealed mRNA for concentrative nucleoside transporter (CNT2), which is a purine nucleoside-selective Na+/nucleoside cotransporter in the epididymis, but not for CNT1. It is suggested that the Na+/nucleoside cotransporter (i.e., CNT2) may be one of the elements involved in Na+ and fluid reabsorption in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa. PMID:11207189

  8. 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. PMID:19692483

  9. Selective reabsorption leading to multiple oscillations in the 8446-A atomic-oxygen laser.

    NASA Technical Reports Server (NTRS)

    Feld, M. S.; Feldman, B. J.; Javan, A.; Domash, L. H.

    1973-01-01

    Laser oscillation of atomic oxygen at 8446 A occurs in four closely spaced lines with peculiar intensity ratios, all detuned from the atomic center frequencies of the three fine-structure transitions. These anomalies are caused by the selective reabsorption of resonance radiation from the lower laser level by ground-state oxygen atoms. The selectivity results from the fact that the velocity distribution of the laser levels is considerably wider than that of the ground state, because of the dissociative mode of production of excited oxygen atoms. Possible extension of this mechanism to the atomic-hydrogen system is discussed.

  10. Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

    PubMed Central

    Liu, Jiang; Kennedy, David J.; Yan, Yanling; Shapiro, Joseph I.

    2012-01-01

    The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption. PMID:22518311

  11. 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. PMID:26804200

  12. Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

    PubMed

    Diamond, G L; Cohen, J J; Weinstein, S L

    1986-11-01

    Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution. PMID:3777178

  13. Vasopressin regulates renal calcium excretion in humans

    PubMed Central

    Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel

    2015-01-01

    Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256

  14. 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.

  15. 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. PMID:23195681

  16. The Effects of Angiotensin II on Renal Water and Electrolyte Excretion in Normal and Caval Dogs*

    PubMed Central

    Porush, Jerome G.; Kaloyanides, George J.; Cacciaguida, Roy J.; Rosen, Stanley M.

    1967-01-01

    The effects of intravenous administration of angiotensin II on renal water and electrolyte excretion were examined during hydropenia, water diuresis, and hypotonic saline diuresis in anesthetized normal dogs and dogs with thoracic inferior vena cava constriction and ascites (caval dogs). The effects of unilateral renal artery infusion of a subpressor dose were also examined. During hydropenia angiotensin produced a decrease in tubular sodium reabsorption, with a considerably greater natriuresis in caval dogs, and associated with a decrease in free water reabsorption (TcH2O). Water and hypotonic saline diuresis resulted in an augmented angiotensin natriuresis, with a greater effect still observed in caval dogs. In these experiments free water excretion (CH2O) was limited to 8-10% of the glomerular filtration rate (GFR), although distal sodium load increased in every instance. In the renal artery infusion experiments a significant ipsilateral decrease in tubular sodium reabsorption was induced, particularly in caval dogs. These findings indicate that angiotensin has a direct effect on renal sodium reabsorption unrelated to a systemic circulatory alteration. The attenuation or prevention of the falls in GFR and effective renal plasma flow (ERPF) usually induced by angiotensin may partially account for the greater natriuretic response in caval dogs and the augmentation during water or hypotonic saline diuresis. However, a correlation between renal hemodynamics and the degree of natriuresis induced was not always present and, furthermore, GFR and ERPF decreased significantly during the intrarenal artery infusion experiments. Therefore, the present experiments indicate that another mechanism is operative in the control of the angiotensin natriuresis and suggest that alterations in intrarenal hemodynamics may play a role. The decrease in TcH2O and the apparent limitation of CH2O associated with an increase in distal sodium load localize the site of action of angiotensin

  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. Mechanisms of compensatory renal growth.

    PubMed

    Cleper, Roxana

    2012-11-01

    Congenitally reduced renal mass- as with agenesis of one kidney, unilateral multicystic dysplastic kidney or with premature birth with early arrest of nephrogenesis- as well as acquired loss of a significant part of kidney tissue- as with kidney donation, after surgery for tumor etc- set in motion compensatory processes with main target to meet metabolic body needs. The sensors for reduced renal mass have not yet been identified. The effectors of the compensatory process include a wide range of growth factors- IGF1, TGF-b1, HGF- and signaling molecules-mTOR- which has intricate reciprocal interactions. As nephrogenesis stops at 34-36 weeks of gestation and can't be restarted thereafter, the main result of this compensatory process is increase in glomerular size (glomerulomegaly) and tubular hypertrophy. Renal volume evaluation by ultrasound is a practical noninvasive tool for assessment of compensatory kidney growth. The increased nephron and kidney size induced by the compensatory process have potential detrimental long-term effect through stretch-induced glomerular cell activation of profibrogenic and vasoconstrictor pathways as well as tubular cell nephrotoxicity caused by abnormal activation of reabsorptive mechanisms including GLUT1 and megalin. Deep understanding of these potentially damage process might help in timely implementation of protective strategies. PMID:23469392

  19. Prostaglandin E2 increases proximal tubule fluid reabsorption, and modulates cultured proximal tubule cell responses via EP1 and EP4 receptors.

    PubMed

    Nasrallah, Rania; Hassouneh, Ramzi; Zimpelmann, Joseph; Karam, Andrew J; Thibodeau, Jean-Francois; Burger, Dylan; Burns, Kevin D; Kennedy, Chris Rj; Hébert, Richard L

    2015-09-01

    Renal prostaglandin (PG) E2 regulates salt and water transport, and affects disease processes via EP1-4 receptors, but its role in the proximal tubule (PT) is unknown. Our study investigates the effects of PGE2 on mouse PT fluid reabsorption, and its role in growth, sodium transporter expression, fibrosis, and oxidative stress in a mouse PT cell line (MCT). To determine which PGE2 EP receptors are expressed in MCT, qPCR for EP1-4 was performed on cells stimulated for 24 h with PGE2 or transforming growth factor beta (TGFβ), a known mediator of PT injury in kidney disease. EP1 and EP4 were detected in MCT, but EP2 and EP3 are not expressed. EP1 was increased by PGE2 and TGFβ, but EP4 was unchanged. To confirm the involvement of EP1 and EP4, sulprostone (SLP, EP1/3 agonist), ONO8711 (EP1 antagonist), and EP1 and EP4 siRNA were used. We first show that PGE2, SLP, and TGFβ reduced H(3)-thymidine and H(3)-leucine incorporation. The effects on cell-cycle regulators were examined by western blot. PGE2 increased p27 via EP1 and EP4, but TGFβ increased p21; PGE2-induced p27 was attenuated by TGFβ. PGE2 and SLP reduced cyclinE, while TGFβ increased cyclinD1, an effect attenuated by PGE2 administration. Na-K-ATPase α1 (NaK) was increased by PGE2 via EP1 and EP4. TGFβ had no effect on NaK. Additionally, PGE2 and TGFβ increased fibronectin levels, reaching 12-fold upon co-stimulation. EP1 siRNA abrogated PGE2-fibronectin. PGE2 also increased ROS generation, and ONO-8711 blocked PGE2-ROS. Finally, PGE2 significantly increased fluid reabsorption by 31 and 46% in isolated perfused mouse PT from C57BL/6 and FVB mice, respectively, and this was attenuated in FVB-EP1 null mice. Altogether PGE2 acting on EP1 and EP4 receptors may prove to be important mediators of PT injury, and salt and water transport. PMID:26121313

  20. 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.

  1. 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.

  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. PMID:26604280

  3. 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

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

    PubMed

    Smith, D F; Shimizu, M

    1978-01-01

    Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity. PMID:692834

  5. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats. PMID:17442729

  6. Localization of GFP-tagged concentrative nucleoside transporters in a renal polarized epithelial cell line.

    PubMed

    Mangravite, L M; Lipschutz, J H; Mostov, K E; Giacomini, K M

    2001-05-01

    Many nucleosides undergo active reabsorption within the kidney, probably via nucleoside transporters. To date, two concentrative nucleoside transporters have been cloned, the sodium-dependent purine-selective nucleoside transporter (SPNT) and concentrative nucleoside transporter 1 (CNT1). We report the stable expression of green fluorescence protein (GFP)-tagged SPNT and CNT1 in Madin-Darby canine kidney (MDCK) cells, a polarized renal epithelial line. We demonstrate that the GFP tag does not alter the substrate selectivity and only modestly affects the kinetic activity of the transporters. By using confocal microscopy and functional studies, both SPNT and CNT1 are localized primarily to the apical membrane of MDCK and LLC-PK(1) cells. Apical localization of these transporters suggests a role in renal nucleoside reabsorption and regulation of tubular function via the adenosine pathway. PMID:11292631

  7. 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. PMID:26170627

  8. Endogenous prostaglandin E2 mediates inhibition of rat thick ascending limb Cl reabsorption in chronic hypercalcemia.

    PubMed Central

    Peterson, L N; McKay, A J; Borzecki, J S

    1993-01-01

    The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC. Images PMID:8390479

  9. Influence of reabsorption and reemission on stimulated Raman scattering of polymethine dyes in multiple scattering media

    SciTech Connect

    Yashchuk, V P; Komyshan, A O; Smaliuk, A P; Prygodiuk, O A; Ishchenko, A A; Olkhovyk, L A

    2013-12-31

    It is shown that reabsorption of the luminescence radiation in the range of its overlapping with the absorption spectrum and the following reemission to a long-wavelength range may noticeably affect the process of stimulated Raman scattering (SRS) in polymethine dyes in multiple scattering media (MSM). This is related to the fact that SRS in such media occurs jointly with the random lasing (RL), which favors SRS and makes up with it a united nonlinear process. Reemission into the long-wavelength spectrum range amplified in MSM causes the RL spectrum to shift to longer wavelengths and initiates the long-wavelength band of RL, in which a main part of the lasing energy is concentrated. This weakens or completely stops the SRS if the band is beyond the range of possible spectral localisation of Stokes lines. This process depends on the efficiency of light scattering, dye concentration, temperature and pump intensity; hence, there exist optimal values of these parameters for obtaining SRS in MSM. (nonlinear optical phenomena)

  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. Renal Function Assessment During Peptide Receptor Radionuclide Therapy.

    PubMed

    Erbas, Belkis; Tuncel, Murat

    2016-09-01

    Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51-ethylenediaminetetraacetic acid (EDTA), or

  12. Renal arteriography

    MedlinePlus

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Update Date 4/7/2014 Updated by: Jason ... Failure Kidney Tests X-Rays Browse the Encyclopedia A. ...

  13. Renal venogram

    MedlinePlus

    ... 2008:chap 6. Rankin S. Renal parenchymal disease, including renal failure, renovascular disease and transportation. In: Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New York, NY: Churchill Livingstone; 2008:chap 39. Read ... arteriography Renal vein thrombosis Tumor Venogram Wilms ...

  14. Renal biomarkers in domestic species.

    PubMed

    Hokamp, Jessica A; Nabity, Mary B

    2016-03-01

    Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies. PMID:26918420

  15. Endocrine and Metabolic Regulation of Renal Drug Transporters

    PubMed Central

    Yacovino, Lindsay L.; Aleksunes, Lauren M.

    2012-01-01

    Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function. PMID:22933250

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

    PubMed

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

    2013-10-01

    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

  17. 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

  18. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

    PubMed Central

    Otto, Edgar A; Schermer, Bernhard; Obara, Tomoko; O'Toole, John F; Hiller, Karl S; Mueller, Adelheid M; Ruf, Rainer G; Hoefele, Julia; Beekmann, Frank; Landau, Daniel; Foreman, John W; Goodship, Judith A; Strachan, Tom; Kispert, Andreas; Wolf, Matthias T; Gagnadoux, Marie F; Nivet, Hubert; Antignac, Corinne; Walz, Gerd; Drummond, Iain A; Benzing, Thomas; Hildebrandt, Friedhelm

    2013-01-01

    Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with β-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and β-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and β-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. PMID:12872123

  19. Role of renal nerves in excretory responses to administration of kappa agonists in conscious spontaneously hypertensive rats.

    PubMed

    Kapusta, D R; Jones, S Y; DiBona, G F

    1989-10-01

    The present study examined whether the renal sympathetic nerves contribute to the renal excretory responses produced by kappa opioid receptor agonist administration in conscious spontaneously hypertensive rats (SHR). Intravenous infusion of the kappa opioid receptor agonists, ketocyclazocine (KC) and U-50488H, produced increases in urine flow rate. KC and U-50488H infusion also resulted in a marked and sustained antinatriuresis which was promptly reversed by low-dose naloxone (50 micrograms/kg i.v.), thus suggesting an opioid receptor-mediated action of both agonists. Although these kappa agonists did not produce changes in glomerular filtration rate or renal plasma flow, efferent renal sympathetic nerve activity increased with the same time course as the antinatriuretic response. To investigate whether the decrease in urinary sodium excretion was mediated via the increase in efferent renal sympathetic nerve activity, experiments were repeated in SHR with prior bilateral renal denervation. These studies demonstrated that similar renal excretory responses (diuresis and a naloxone reversible antiinatriuresis occurred during infusion of KC and U-50488H in renal denervated as were seen in intact SHR. These studies indicate that the renal excretory responses to the kappa opioid agonists KC and U-50488H are not mediated through changes in renal hemodynamics or via a pathway requiring intact renal innervation. Because an antinatriuretic response was observed in renal denervated SHR, this suggests that kappa opioid receptor agonists may influence the renal tubular reabsorption of sodium by additional naloxone-sensitive mechanisms independent of intact renal innervation. PMID:2552076

  20. Roles of organic anion transporters in the progression of chronic renal failure.

    PubMed

    Enomoto, Atsushi; Niwa, Toshimitsu

    2007-10-01

    Renal proximal and distal tubules carry out specialized directional transport of various solutes. The family of organic anion transporters (OATs), which belongs to the major facilitator superfamily (SLC22A), are expressed in the renal epithelial cells to regulate the excretion and the reabsorption of endogenous and exogenous organic anions that include various kinds of drugs and their metabolites. In recent years, it is revealed that indoxyl sulfate, one of uremic toxins, is a novel physiological substrate for OAT family, and its accumulation within the renal tubules via OATs induces renal dysfunction. The OATs are also expressed in the blood-brain barrier, muscle cells, and bone osteoblasts, which hint at various pathogenic roles of OAT-mediated transport of uremic toxins. In this review, we introduce and discuss the function of OATs in the context of their roles in the progression of chronic renal disease. PMID:17976081

  1. 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.

  2. Renal functional reserve in pigs: renal haemodynamics, renal tubular function and salt and water homeostatic hormones during amino acid and dopamine stimulation.

    PubMed

    Poulsen, E U; Frøkiaer, J; Jørgensen, T M; Pedersen, E B; Rehling, M

    1997-01-01

    The purpose of the study was to evaluate renal functional reserve [RFR is the difference between glomerular filtration rate (GFR) at rest and maximal GFR after stimulation] in a controlled study in normal pigs. Our basic hypothesis was that a decreased RFR may be used as an early indicator of renal deterioration, i.e. a test to disclose significant obstruction as opposed to simple dilatation in hydronephrosis. During various forms of stimulation (amino acids, captopril and dopamine), we measured changes in GFR, renal plasma flow (RPF), tubular reabsorption of sodium and water, net uptake from plasma to the kidney of three salt and water homeostatic hormones (angiotensin II, aldosterone and atrial natriuretic peptide) and of glucagon, which is thought to play a key role as mediator of the GFR increase during amino acid infusion. We found the largest GFR increase during combined infusion of amino acids and dopamine (+13%), but compared with a non-stimulated control group, the GFR increase was statistically non-significant. RPF increased by 57% during stimulation with amino acids plus dopamine (P < 0.001), while tubular reabsorption of sodium and water, and renal uptake of angiotensin II, aldosterone and atrial natriuretic peptide showed no significant differences between control and stimulation groups. The renal uptake of glucagon increased significantly during amino acid stimulation with no concomitant GFR increase. We conclude that in this experimental, non-obstructed model, RFR is a very insensitive measure, which cannot be used to discriminate between obstruction and simple dilatation in hydronephrosis. Further, our study does not support the hypothesis that glucagon is involved in GFR changes after amino acids. PMID:9015658

  3. Impaired Lysosomal Function Underlies Monoclonal Light Chain-Associated Renal Fanconi Syndrome.

    PubMed

    Luciani, Alessandro; Sirac, Christophe; Terryn, Sara; Javaugue, Vincent; Prange, Jenny Ann; Bender, Sébastien; Bonaud, Amélie; Cogné, Michel; Aucouturier, Pierre; Ronco, Pierre; Bridoux, Frank; Devuyst, Olivier

    2016-07-01

    Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS. PMID:26614382

  4. 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. PMID:26123779

  5. 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

  6. Localization of Tubular Adaptation to Renal Sodium Loss in Gitelman Syndrome

    PubMed Central

    Nau, Valérie; Kolb, Isabelle; Vargas-Poussou, Rosa; Hannedouche, Thierry; Moulin, Bruno

    2012-01-01

    Summary Background and objectives Gitelman syndrome (GS) is a salt-wasting tubulopathy that results from the inactivation of the human thiazide–sensitive sodium chloride cotransporter located in the distal convoluted tubule. Tubular adaptation to renal sodium loss has been described and localized in the distal tubule in experimental models of GS but not in humans with GS. Design, setting, participants, & measurements The tubular adaptation to renal sodium loss is described. Osmole-free water clearance and endogenous lithium clearance with furosemide infusion are used to compare 7 patients with genetically confirmed GS and 13 control participants. Results Neither endogenous lithium clearance nor osmole-free water clearance disclosed enhanced proximal fluid reabsorption in patients with GS. These patients displayed significantly lower osmole-free water clearance factored by inulin clearance (7.1±1.9 versus 10.1±2.2; P<0.01) and significantly lower fractional sodium reabsorption in the diluting nephron (73.2%±7.1% versus 86.1%±4.7%; P<0.005), consistent with the inactivation of the thiazide-sensitive sodium chloride cotransporter. The furosemide-induced reduction rate of fractional sodium reabsorption in the diluting segment was higher in patients with GS (75.6%±6.1% versus 69.9%±3.2%; P<0.039), suggesting that sodium reabsorption would be enhanced in the cortical part of the thick ascending limb of the loop of Henle in patients with GS. Conclusions These findings suggest that tubular adaptation to renal sodium loss in GS would be devoted to the cortical part of the thick ascending limb of the loop of Henle in humans. PMID:22241817

  7. Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

    PubMed Central

    Satoh, Nobuhiko; Nakamura, Motonobu; Suzuki, Masashi; Suzuki, Atsushi; Seki, George; Horita, Shoko

    2015-01-01

    A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2) and stimulates sodium-bicarbonate cotransporter (NBCe1), resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC) and epithelial sodium channel (ENaC) activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK). Moreover, sodium-proton exchanger 3 (NHE3) in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport. PMID:26491696

  8. Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport.

    PubMed

    Satoh, Nobuhiko; Nakamura, Motonobu; Suzuki, Masashi; Suzuki, Atsushi; Seki, George; Horita, Shoko

    2015-01-01

    A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2) and stimulates sodium-bicarbonate cotransporter (NBCe1), resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC) and epithelial sodium channel (ENaC) activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK). Moreover, sodium-proton exchanger 3 (NHE3) in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport. PMID:26491696

  9. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease.

    PubMed

    Ow, Connie P C; Abdelkader, Amany; Hilliard, Lucinda M; Phillips, Jacqueline K; Evans, Roger G

    2014-11-15

    Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney. PMID:25209412

  10. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia

    PubMed Central

    Carpenter, Thomas O.; Imel, Erik A.; Ruppe, Mary D.; Weber, Thomas J.; Klausner, Mark A.; Wooddell, Margaret M.; Kawakami, Tetsuyoshi; Ito, Takahiro; Zhang, Xiaoping; Humphrey, Jeffrey; Insogna, Karl L.; Peacock, Munro

    2014-01-01

    Background. X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate reabsorption, and low serum concentrations of phosphate (inorganic phosphorus, Pi) and 1,25-dihydroxyvitamin D [1,25(OH)2D]. KRN23 is a human anti-FGF23 antibody developed as a potential treatment for XLH. Here, we have assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of KRN23 following a single i.v. or s.c. dose of KRN23 in adults with XLH. Methods. Thirty-eight XLH patients were randomized to receive a single dose of KRN23 (0.003–0.3 mg/kg i.v. or 0.1–1 mg/kg s.c.) or placebo. PK, PD, immunogenicity, safety, and tolerability were assessed for up to 50 days. Results. KRN23 significantly increased the maximum renal tubular threshold for phosphate reabsorption (TmP/GFR), serum Pi, and 1,25(OH)2D compared with that of placebo (P < 0.01). The maximum serum Pi concentration occurred later following s.c. dosing (8–15 days) compared with that seen with i.v. dosing (0.5–4 days). The effect duration was dose related and persisted longer in patients who received s.c. administration. Changes from baseline in TmP/GFR, serum Pi, and serum 1,25(OH)2D correlated with serum KRN23 concentrations. The mean t1/2 of KRN23 was 8–12 days after i.v. administration and 13–19 days after s.c. administration. Patients did not exhibit increased nephrocalcinosis or develop hypercalciuria, hypercalcemia, anti-KRN23 antibodies, or elevated serum parathyroid hormone (PTH) or creatinine. Conclusion. KRN23 increased TmP/GFR, serum Pi, and serum 1,25(OH)2D. The positive effect of KR23 on serum Pi and its favorable safety profile suggest utility for KRN23 in XLH patients. Trial registration. Clinicaltrials.gov NCT00830674. Funding. Kyowa Hakko Kirin Pharma, Inc. PMID:24569459

  11. 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

  12. [Renal elastography].

    PubMed

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  13. 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

  14. 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

  15. 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

  16. Measurement of the helium 23S metastable atom density by observation of the change in the 23S-23P emission line shape due to radiation reabsorption

    NASA Astrophysics Data System (ADS)

    Shikama, T.; Ogane, S.; Iida, Y.; Hasuo, M.

    2016-01-01

    In helium discharge plasmas, the relative emission intensities of the fine-structure transitions belonging to the HeI 23S-23P transition can be affected by radiation reabsorption. Since the magnitude of the reabsorption depends on the density and temperature of the 23S metastable atoms, their density can be determined by measuring the 23S-23P emission line shape using a high wavelength-resolution spectrometer. In this study, the applicable conditions of the method in terms of the opacity and line broadening are revealed, and possible causes of errors in the measurement, i.e. spatial distributions of the density and temperature and the effects of external magnetic and electric fields, are investigated. The effect of reabsorption under an external magnetic field is experimentally confirmed using a glow discharge plasma installed in a superconducting magnet.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23828583

  18. Role of renal nerves in excretory responses to exogenous and endogenous opioid peptides.

    PubMed

    Kapusta, D R; Jones, S Y; Kopp, U C; Dibona, G F

    1989-03-01

    The present study was designed to investigate opioid peptide-mediated changes in renal function in conscious Sprague-Dawley rats after administration of the native opioid agonist methionine enkephalin (ME), its synthetic analog D-Ala2-methionine enkephalinamide (DALA) and the opioid antagonist naloxone. Intravenous infusion of DALA (25 micrograms/kg/min) and ME (75 micrograms/kg/min) produced no changes in mean arterial pressure, heart rate, glomerular filtration rate or effective renal plasma flow in rats with intact or bilaterally denervated kidneys. In contrast, i.v. infusion of these opioid agonists produced differing effects on the renal excretion of water and sodium; DALA produced an increase in urinary flow rate and sodium excretion and ME produced a decrease in these parameters. Changes in renal sympathetic nerve activity were not involved in producing these effects as supported by measurements of renal sympathetic nerve activity and the finding that prior bilateral renal denervation did not alter the renal responses to either agonist. The renal excretory responses to both DALA and ME infusion were prevented by pretreatment with the opioid receptor antagonist naloxone, thus suggesting an opioid receptor-mediated effect of both agonists. Intravenous bolus injections of naloxone alone produced a dose-dependent diuresis and natriuresis without producing changes in systemic or renal hemodynamics or renal sympathetic nerve activity. These studies, therefore, provide evidence that the administration of opioid receptor agonists and antagonists produce changes in the renal excretion of water and sodium via an action on renal tubular reabsorptive mechanisms which are independent of changes in systemic or renal hemodynamics or renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2703962

  19. Time course and localization of endothelin-1 gene expression in a model of renal disease progression.

    PubMed Central

    Bruzzi, I.; Corna, D.; Zoja, C.; Orisio, S.; Schiffrin, E. L.; Cavallotti, D.; Remuzzi, G.; Benigni, A.

    1997-01-01

    Experimental and human proteinuric glomerulopathies are associated with tubulo-interstitial injury that correlates with the decline of renal function even better than glomerular lesions do. Mechanism(s) leading to tubulo-interstitial damage are unknown. It has been proposed that excessive reabsorption of filtered proteins activates renal cells to produce vasoactive and inflammatory molecules including endothelin-1. The aim of the present study was twofold: we first evaluated the cellular origin of excessive renal endothelin-1 production in the renal mass reduction model and then related endothelin-1 distribution to the development of kidney lesions. Four groups of renal mass reduction (n = 15) and four groups of control rats (n = 5) were studied at 7, 14, 21, and 28 days after surgery. Urinary proteins in renal mass reduction rats were comparable with controls at day 7 but became significantly higher thereafter. Renal mass reduction rats first developed tubulo-interstitial changes, which were already evident at day 14 in the majority of them. At 28 days, renal mass reduction rats also developed glomerulosclerosis. A parallel increase of renal endothelin-1 gene expression and synthesis of the corresponding peptide in renal mass reduction rats versus controls was observed from day 14. Nonradioactive in situ hybridization confirmed a pattern of endothelin-1 mRNA consistent with the distribution of lesions. At day 14, endothelin-1 staining was stronger in renal mass reduction than in control kidneys and mainly localized to the cytoplasm of tubular cells, whereas glomeruli were negative. At day 28, endothelin-1 expression further increased in renal mass reduction rats as compared with controls, and the staining was apparent also in glomeruli. Thus, in renal mass reduction, a progressive up-regulation of endothelin-1 occurs during the development of renal injury, that first involves the tubules and, only in a subsequent phase, the glomeruli. Images Figure 2 PMID:9358749

  20. 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

  1. Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

    PubMed Central

    Mlcochova, Hana; Machackova, Tana; Rabien, Anja; Radova, Lenka; Fabian, Pavel; Iliev, Robert; Slaba, Katerina; Poprach, Alexandr; Kilic, Ergin; Stanik, Michal; Redova-Lojova, Martina; Svoboda, Marek; Dolezel, Jan; Vyzula, Rostislav; Jung, Klaus; Slaby, Ondrej

    2016-01-01

    Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro. PMID:27549611

  2. Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.

    PubMed

    Mlcochova, Hana; Machackova, Tana; Rabien, Anja; Radova, Lenka; Fabian, Pavel; Iliev, Robert; Slaba, Katerina; Poprach, Alexandr; Kilic, Ergin; Stanik, Michal; Redova-Lojova, Martina; Svoboda, Marek; Dolezel, Jan; Vyzula, Rostislav; Jung, Klaus; Slaby, Ondrej

    2016-01-01

    Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro. PMID:27549611

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

    PubMed

    Kurozumi, Akira; Kato, Mayuko; Goto, Yusuke; Matsushita, Ryosuke; Nishikawa, Rika; Okato, Atsushi; Fukumoto, Ichiro; Ichikawa, Tomohiko; Seki, Naohiko

    2016-05-01

    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

  4. Paradoxical effects of green tea (Camellia sinensis) and antioxidant vitamins in diabetic rats: improved retinopathy and renal mitochondrial defects but deterioration of collagen matrix glycoxidation and cross-linking.

    PubMed

    Mustata, Georgian T; Rosca, Mariana; Biemel, Klaus M; Reihl, Oliver; Smith, Mark A; Viswanathan, Ashwini; Strauch, Christopher; Du, Yunpeng; Tang, Jie; Kern, Timothy S; Lederer, Markus O; Brownlee, Michael; Weiss, Miriam F; Monnier, Vincent M

    2005-02-01

    We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma were increased by diabetes (P < 0.001) but unaffected by treatment. Erythrocyte glutathione and plasma hydroperoxides were improved by the vitamins (P < 0.05) and green tea (P < 0.001). Retinal superoxide production, acellular capillaries, and pericyte ghosts were increased by diabetes (P < 0.001) and improved by green tea and the vitamins (P variable). Lens crystallin fluorescence at 370/440 nm was ameliorated by green tea (P < 0.05) but not the vitamins. Marginal effects on nephropathy parameters were noted. However, suppressed renal mitochondrial NADH-linked ADP-dependent and dinitrophenol-dependent respiration and complex III activity were improved by green tea (P variable). Green tea also suppressed the methylglyoxal hydroimidazolone immunostaining of a 28-kDa mitochondrial protein. Surprising, glycoxidation in tendon, aorta, and plasma was either worsened or not significantly improved by the vitamins and green tea. Glucosepane cross-links were increased by diabetes (P < 0.001), and green tea worsened total cross-linking. In conclusion, green tea and antioxidant vitamins improved several diabetes-related cellular dysfunctions but worsened matrix glycoxidation in selected tissues, suggesting that antioxidant treatment tilts the balance from oxidative to carbonyl stress in the extracellular compartment. PMID:15677510

  5. Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

    PubMed Central

    Beck, N; Kim, K S; Wolak, M; Davis, B B

    1975-01-01

    It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system. PMID:233968

  6. 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

  7. Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides

    SciTech Connect

    Williams, P.D.; Hottendorf, G.H.; Bennett, D.B.

    1986-06-01

    The initial event in the renal tubular reabsorption of nephrotoxic aminoglycosides involves binding to brush border membranes. This primary event was measured in renal brush border membrane vesicles prepared from rat renal cortex utilizing (3H)gentamicin. In order to gain structure-activity information regarding this interaction the effect of substances having chemical similarities to aminoglycosides (sugars, polyamines and amino acids) on gentamicin binding to brush border membranes was determined. Polyamino acids were found to possess the greatest inhibitory potency. In addition to polymers of cationic amino acids (lysine, ornithine, arginine and histidine), polymers of neutral (asparagine) and acidic (aspartic and glutamic acid) amino acids also exhibited inhibition of the membrane binding of gentamicin. Inasmuch as inhibition of renal membrane binding has the potential to decrease aminoglycoside nephrotoxicity, several polyamino acids that inhibited membrane binding were tested in vivo for potential protective activity vs. gentamicin- and amikacin-induced nephrotoxicity. Polyasparagine90 and polyaspartic acid100 inhibited gentamicin and amikacin nephrotoxicity completely when coadministered to rats with the aminoglycosides. Polylysine20 provided complete and partial inhibition of gentamicin and amikacin nephrotoxicity, respectively. Whereas in vivo distribution studies revealed that cortical levels of (3H)amikacin were elevated slightly by the coadministration of polyaspartic acid, brush border and basolateral membranes contained significantly lower levels of the aminoglycoside (46 and 41% inhibition, respectively). These results question the role of charge per se in the binding of aminoglycosides to renal membranes and further confirm the importance of membrane binding in the pathogenesis of aminoglycoside nephrotoxicity.

  8. [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. PMID:25782287

  9. Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP Signaling.

    PubMed

    Blanchard, Maxime G; Kittikulsuth, Wararat; Nair, Anil V; de Baaij, Jeroen H F; Latta, Femke; Genzen, Jonathan R; Kohan, Donald E; Bindels, René J M; Hoenderop, Joost G J

    2016-03-01

    The transient receptor potential melastatin type 6 (TRPM6) epithelial Mg(2+) channels participate in transcellular Mg(2+) transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg(2+) reabsorption in the kidney. The molecular details of this process are, however, unknown. Adenylate cyclase 3 (Adcy3) has been shown to colocalize with the Na(+)/Cl(-) cotransporter, a marker of the distal convoluted segment of the kidney, the principal site of TRPM6 expression. Given the critical role of TRPM6 in Mg(2+) reabsorption, an inducible kidney-specific Adcy3 deletion mouse model was characterized for blood and urinary electrolyte disturbances under a normal--and low--Mg(2+) diet. Increased urinary Mg(2+) wasting and Trpm6 mRNA levels were observed in the urine and kidney of Adcy3-deleted animals compared with wild-type controls. Serum Mg(2+) concentration was significantly lower in Adcy3-deleted animals at day 7 on the low Mg(2+) diet. Using patch clamp electrophysiology, cell surface biotinylation, and total internal reflection fluorescence live cell imaging of transfected HEK293 cells, we demonstrated that cAMP signaling rapidly potentiates TRPM6 activity by promoting TRPM6 accumulation at the plasma membrane and increasing its single-channel conductance. Comparison of electrophysiological data from cells expressing the phosphorylation-deficient S1252A or phosphomimetic S1252D TRPM6 mutants suggests that phosphorylation at this intracellular residue participates in the observed stimulation of channel activity. Altogether, these data support a physiologically relevant magnesiotropic role of cAMP signaling in the kidney by a direct stimulatory action of protein kinase A on the plasma membrane trafficking and function of TRPM6 ion channels. PMID:26150606

  10. Fluid reabsorption in proximal convoluted tubules of mice with gene deletions of claudin-2 and/or aquaporin1

    PubMed Central

    Huang, Yuning; Mizel, Diane

    2013-01-01

    Deletions of claudin-2 (Cldn2) and aquaporin1 (AQP1) reduce proximal fluid reabsorption (PFR) by about 30% and 50%, respectively. Experiments were done to replicate these observations and to determine in AQP1/claudin-2 double knockout mice (DKO) if the effects of deletions of these established water pores are additive. PFR was determined in inactin/ketamine-anesthetized mice by free-flow micropuncture using single-nephron I125-iothalamate (io) clearance. Animal means of PFR [% of glomerular filtration rate (GFR)] derived from TF/Piothalamate ratios in 12 mice in each of four groups [wild type (WT), Cldn2−/−, AQP1−/−, and DKO) were 45.8 ± 0.85 (51 tubules), 35.4 ± 1 (54 tubules; P < 0.01 vs. WT), 36.8 ± 1 (63 tubules; P < 0.05 vs. WT), and 33.9 ± 1.4 (69 tubules; P < 0.01 vs. WT). Kidney and single-nephron GFRs (SNGFR) were significantly reduced in all mutant strains. The direct relationship between PFR and SNGFR was maintained in mutant mice, but the slope of this relationship was reduced in the absence of Cldn2 and/or AQP1. Transtubular osmotic pressure differences were not different between WT and Cldn2−/− mice, but markedly increased in DKO. In conclusion, the deletion of Cldn2, AQP1, or of both Cldn2 and AQP1 reduces PFR by 22.7%, 19.6%, and 26%, respectively. Our data are consistent with an up to 25% paracellular contribution to PFR. The reduced osmotic water permeability caused by absence of AQP1 augments luminal hypotonicity. Aided by a fall in filtered load, the capacity of non-AQP1-dependent transcellular reabsorption is sufficient to maintain PFR without AQP1 and claudin-2 at 75% of control. PMID:24049145

  11. 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. PMID:22132964

  12. Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1.

    PubMed

    Artunc, Ferruh; Amann, Kerstin; Nasir, Omaima; Friedrich, Björn; Sandulache, Diana; Jahovic, Nermina; Risler, Teut; Vallon, Volker; Wulff, Peer; Kuhl, Dietmar; Lang, Florian

    2006-09-01

    Mineralocorticoids stimulate renal tubular Na(+) reabsorption, enhance salt appetite, increase blood pressure, and favor the development of renal fibrosis. The effects of mineralocorticoids on renal tubular Na(+) reabsorption and salt appetite involve the serum- and glucocorticoid-inducible kinase 1 (SGK1). The kinase is highly expressed in fibrosing tissue. The present experiments thus explored the involvement of SGK1 in renal fibrosis. To this end, SGK1-knockout mice (sgk1 (-/-)) and their wild-type littermates (sgk1 (+/+)) were implanted with desoxycorticosterone acetate (DOCA)-release pellets and offered 1% saline as drinking water for 12 weeks. The treatment led to significant increases in fluid and Na(+) intake and urinary output of fluid and Na(+) in sgk1 (+/+) mice, effects blunted in sgk1 (-/-) mice. Blood pressure increased within the first 7 weeks to a similar extent in both genotypes, but within the next 5 weeks, it increased further only in sgk1 (+/+) mice. Creatinine clearance did not change significantly but albuminuria increased dramatically in sgk1 (+/+) mice, an effect significantly blunted in sgk1 (-/-) mice. Histology after 12 weeks treatment revealed marked glomerular sclerosis and tubulointerstitial damage with interstitial fibrosis and inflammation in kidneys from sgk1 (+/+) mice, but not from sgk1 (-/-) mice. In conclusion, a lack of SGK1 protects against DOCA/high-salt-induced albuminuria and renal fibrosis. PMID:16924469

  13. [Renal disease].

    PubMed

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  14. Renal organogenesis

    PubMed Central

    2011-01-01

    The increasing prevalence of chronic kidney disease in the absence of new treatment modalities has become a strong driver for innovation in nephrology. An increasing understanding of stem cell biology has kindled the prospects of regenerative options for kidney disease. However, the kidney itself is not a regenerative organ, as all the nephrons are formed during embryonic development. Here, we will investigate advances in the molecular genetics of renal organogenesis, including what this can tell us about lineage relationships, and discuss how this may serve to inform us about both the normal processes of renal repair and options for regenerative therapies. PMID:22198432

  15. [Renal colic].

    PubMed

    Pinheiro, J M

    1999-01-01

    The appropriate approach to renal colic, which should be known by the family doctor, is presented. The incidence of this condition in the emergency department of a large general hospital is described as well as the physiopathology of pain, its clinical aspects and the therapeutic attitudes. Renal colic is frequent, it is often possible to diagnose the clinical aspects and general practitioners have the competence for treatment. The use of analgesic drugs, in the correct dosage, is enough to relieve pain and suffering in most of the patients. PMID:10423866

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

    PubMed Central

    Subramanian, Veedamali S.; Subramanya, Sandeep B.; Tsukamoto, Hidekazu

    2010-01-01

    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. PMID:20427470

  17. 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. PMID:22941874

  18. 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. PMID:26740184

  19. Crafting Core/Graded Shell-Shell Quantum Dots with Suppressed Re-absorption and Tunable Stokes Shift as High Optical Gain Materials.

    PubMed

    Jung, Jaehan; Lin, Chun Hao; Yoon, Young Jun; Malak, Sidney T; Zhai, Yaxin; Thomas, Edwin L; Vardeny, Valy; Tsukruk, Vladimir V; Lin, Zhiqun

    2016-04-11

    The key to utilizing quantum dots (QDs) as lasing media is to effectively reduce non-radiative processes, such as Auger recombination and surface trapping. A robust strategy to craft a set of CdSe/Cd1-x Znx Se1-y Sy /ZnS core/graded shell-shell QDs with suppressed re-absorption, reduced Auger recombination rate, and tunable Stokes shift is presented. In sharp contrast to conventional CdSe/ZnS QDs, which have a large energy level mismatch between CdSe and ZnS and thus show strong re-absorption and a constrained Stokes shift, the as-synthesized CdSe/Cd1-x Znx Se1-y Sy /ZnS QDs exhibited the suppressed re-absorption of CdSe core and tunable Stokes shift as a direct consequence of the delocalization of the electron wavefunction over the entire QD. Such Stokes shift-engineered QDs with suppressed re-absorption may represent an important class of building blocks for use in lasers, light emitting diodes, solar concentrators, and parity-time symmetry materials and devices. PMID:26990250

  20. Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis.

    PubMed Central

    Kalluri, R; Shield, C F; Todd, P; Hudson, B G; Neilson, E G

    1997-01-01

    Normal glomerular capillaries filter plasma through a basement membrane (GBM) rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now show that these latter isoforms are absent biochemically from the glomeruli in patients with X-linked Alport syndrome (XAS). Their GBM instead retain a fetal distribution of alpha1(IV) and alpha2(IV) isoforms because they fail to developmentally switch their alpha-chain use. The anomalous persistence of these fetal isoforms of type IV collagen in the GBM in XAS also confers an unexpected increase in susceptibility to proteolytic attack by collagenases and cathepsins. The incorporation of cysteine-rich alpha3(IV), alpha4(IV), and alpha5(IV) chains into specialized basement membranes like the GBM may have normally evolved to protectively enhance their resistance to proteolytic degradation at the site of glomerular filtration. The relative absence of these potentially protective collagen IV isoforms in GBM from XAS may explain the progressive basement membrane splitting and increased damage as these kidneys deteriorate. PMID:9153291

  1. 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

  2. CNNM2, Encoding a Basolateral Protein Required for Renal Mg2+ Handling, Is Mutated in Dominant Hypomagnesemia

    PubMed Central

    Stuiver, Marchel; Lainez, Sergio; Will, Constanze; Terryn, Sara; Günzel, Dorothee; Debaix, Huguette; Sommer, Kerstin; Kopplin, Kathrin; Thumfart, Julia; Kampik, Nicole B.; Querfeld, Uwe; Willnow, Thomas E.; Němec, Vladimír; Wagner, Carsten A.; Hoenderop, Joost G.; Devuyst, Olivier; Knoers, Nine V.A.M.; Bindels, René J.; Meij, Iwan C.; Müller, Dominik

    2011-01-01

    Familial hypomagnesemia is a rare human disorder caused by renal or intestinal magnesium (Mg2+) wasting, which may lead to symptoms of Mg2+ depletion such as tetany, seizures, and cardiac arrhythmias. Our knowledge of the physiology of Mg2+ (re)absorption, particularly the luminal uptake of Mg2+ along the nephron, has benefitted from positional cloning approaches in families with Mg2+ reabsorption disorders; however, basolateral Mg2+ transport and its regulation are still poorly understood. Here, by using a candidate screening approach, we identified CNNM2 as a gene involved in renal Mg2+ handling in patients of two unrelated families with unexplained dominant hypomagnesemia. In the kidney, CNNM2 was predominantly found along the basolateral membrane of distal tubular segments involved in Mg2+ reabsorption. The basolateral localization of endogenous and recombinant CNNM2 was confirmed in epithelial kidney cell lines. Electrophysiological analysis showed that CNNM2 mediated Mg2+-sensitive Na+ currents that were significantly diminished in mutant protein and were blocked by increased extracellular Mg2+ concentrations. Our data support the findings of a recent genome-wide association study showing the CNNM2 locus to be associated with serum Mg2+ concentrations. The mutations found in CNNM2, its observed sensitivity to extracellular Mg2+, and its basolateral localization signify a critical role for CNNM2 in epithelial Mg2+ transport. PMID:21397062

  3. 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.

  4. Renal Transporter-Mediated Drug-Drug Interactions: Are They Clinically Relevant?

    PubMed

    Lepist, Eve-Irene; Ray, Adrian S

    2016-07-01

    The kidney, through the distinct processes of passive glomerular filtration and active tubular secretion, plays an important role in the elimination of numerous endobiotics (eg, hormones, metabolites), toxins, nutrients, and drugs. Renal transport pathways mediating active tubular secretion and reabsorption in the proximal tubule are complex, involving apical and basolateral transporters acting in concert. Detailed studies of the molecular mechanisms of net active tubular secretion have established the involvement of multiple transporters with overlapping substrate specificity mediating competing secretion and reabsorption pathways. Although drug interactions arising from inhibition of renal transporters are rare relative to other mechanisms, they can involve commonly administered drugs (eg, cimetidine, metformin), may be underappreciated due to muted effects on plasma pharmacokinetics relative to tissue levels, can affect narrow-therapeutic-index medications (eg, antiarrhythmic, oncology medications), and may disproportionately affect sensitive populations where polypharmacy is common (eg, the elderly, diabetics). In particular, there is the potential for larger-magnitude interactions in subjects with reduced glomerular filtration rates due to the increased relative contribution of tubular secretion. The assessment of additional endpoints in drug-drug interaction studies including pharmacodynamics, positron emission tomography imaging, and metabolomics promises to expand our understanding of the clinical relevance of renal drug interactions. PMID:27385181

  5. 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. PMID:25767285

  6. 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

  7. Effects of morphine on the renal handling of sodium and lithium in conscious rats.

    PubMed

    el-Awady, E S; Walker, L A

    1990-09-01

    The present study was carried out in order to assess the renal response to i.v. morphine in the rat, particularly the effects on tubular handling of sodium and lithium. Rats were prepared surgically with arterial and venous catheters and bladder cannulas. Clearance experiments and measurements of blood pressure and heart rate were carried out at least 4 days after surgery in unanesthetized animals. Intravenous administration of morphine (4 mg/kg b.wt.) caused a decrease in fractional sodium excretion, (at 90 min after injection, vehicle, 2.49 +/- 0.30% vs. morphine, 1.12 +/- 0.17%, P less than .05), in the absence of significant changes in systemic hemodynamics or glomerular filtration rate. This effect was prevented by pretreatment with naloxone. Enhanced proximal tubular reabsorption of sodium was considered as a possible explanation for the decrease in sodium excretion which followed morphine administration. Proximal tubular fluid reabsorption was estimated utilizing the lithium clearance method. Results indicated a reduction in fractional excretion of lithium by morphine administration (at 90 min, vehicle, 34.2 +/- 3.3% vs. morphine, 18.8 +/- 2.3%, P less than .05), which was also prevented by naloxone pretreatment. It is concluded that, under the present experimental conditions, morphine enhances tubular reabsorption of sodium by an opiate receptor-dependent mechanism and that this effect is, at least in part, localized in the proximal tubule. PMID:2395123

  8. 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. PMID:25613995

  9. Perinatal Taurine Alters Arterial Pressure Control and Renal Function in Adult Offspring

    PubMed Central

    Roysommuti, Sanya; Lerdweeraphon, Wichaporn; Malila, Pisamai; Jirakulsomchok, Dusit; Wyss, J. Michael

    2009-01-01

    The present study investigates the effect of perinatal taurine exposure on renal function in adult, female rats on a high sugar diet. Perinatal taurine depleted (TD), supplemented (TS) or untreated control (C) female offspring were fed normal rat chow and tap water (CW,TDW or TSW) or tap water with 5% glucose (CG, TDG or TSG) after weaning. At 7–8 weeks of age, renal function was studied in the conscious, restrained rats. Mean arterial pressure was significantly higher in TDW, TDG, and TSG rats. Plasma sodium concentration was significantly lower in all glucose treated animals, but the greatest decrease was in TDW rats. Basal renal blood flow was lowest in TSW and TSG, and the responses to a saline load were also lowest in those two groups. These changes were consistent with increased renal vascular resistance. The basal glomerular filtration rate was lowest in TSW, but the responses to a saline load were similar in all of the groups. Water excretion was lower in TSG and TSW, consistent with increased renal tubular water reabsorption. These data suggest that perinatal taurine exposure alters normal renal function and renal responses to dietary sugar in adult female offspring. PMID:19239145

  10. 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. PMID:26511649

  11. Renal Fibrosis

    PubMed Central

    Zeisberg, Michael; Maeshima, Yohei; Mosterman, Barbara; Kalluri, Raghu

    2002-01-01

    During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-β1-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-β1/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-β1/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-β1-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions. PMID:12057905

  12. 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

  13. STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb

    PubMed Central

    Yoon, Joonho; Baum, Michel; Huang, Chou-Long

    2014-01-01

    SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase] kinase consists of a full-length (FL-) and an alternatively spliced kidney-specific (KS-) isoform. SPAK regulates the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). The relative abundance and role of FL- vs. KS-SPAK in regulating Na+-K+-2Cl− cotransporter (NKCC2) in thick ascending limb (TAL) are not completely understood. Here, we report that FL-SPAK mRNA was the most abundant in medullary TAL (mTAL), followed by cortical TAL (cTAL) and DCT. KS-SPAK mRNA abundance was relatively lower than FL-SPAK. The ratios of FL-SPAK to KS-SPAK in mTAL, cTAL, and DCT were 12.3, 12.5, and 10.2, respectively. To examine the role of SPAK in the regulation of sodium transport in TAL, we used in vitro microperfusion of mTAL and cTAL isolated from wild-type (WT) and SPAK knockout mice (SPAK-KO) that lack both FL- and KS-SPAK. The rates of sodium absorption in cTAL and mTAL of SPAK-KO mice were 34.5 and 12.5% of WT tubules, respectively. The mRNA levels of related OSR1 kinase and SPAK protease Dnpep in SPAK-KO tubules were not significantly different from WT tubules. We next examined the role of SPAK in the regulation of sodium reabsorption by vasopressin in TAL. Vasopressin increased sodium reabsorption by ∼80% in both mTAL and cTAL from WT mice. While baseline sodium reabsorption was lower in SPAK-KO tubules, vasopressin increased sodium reabsorption over twofold. In conclusion, the combined net effect of SPAK isoforms on sodium reabsorption in TAL is stimulatory. SPAK is not essential for vasopressin stimulation of sodium reabsorption in TAL. PMID:25477470

  14. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.

    PubMed

    Buishas, Joel; Gould, Ian G; Linninger, Andreas A

    2014-10-01

    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

  15. New insights into diuretic use in patients with chronic renal disease.

    PubMed

    Wilcox, Christopher S

    2002-03-01

    Patients with chronic renal insufficiency (CRI) or the nephrotic syndrome frequently manifest diuretic resistance. Factors limiting diuretic responsiveness in patients with CRI may include a reduced basal level of fractional Na(+) reabsorption that places an upper limit on diuretic response, and enhanced NaCl reabsorption in downstream segments, combined with a reduced delivery of diuretic to the kidney. Diuretics are secreted by the recently characterized organic anion transporters (OATs), which are expressed in proximal tubule cells. Secretion may be inhibited by retained organic anions, urate, or acidosis. These limitations necessitate an increased diuretic dosage, up to a defined ceiling level, and consideration of the use of a nonrenally metabolized loop diuretic rather than furosemide. Diuretic responsiveness in patients with the nephrotic syndrome is limited by avid Na(+) reabsorption by the terminal nephron. Experimental studies have shown that a reduced serum albumin concentration can increase the volume of distribution of loop diuretics, reduce their tubular secretion, and enhance the inactivation of furosemide within the kidney by glucuronidization. Binding of loop diuretics can curtail their action in the loop of Henle. Recent clinical investigations have challenged the importance of some of these mechanisms that were identified in animal models. Strategies to improve loop diuretic responsiveness include increasing diuretic dosage, concurrent use of a thiazide diuretic to inhibit downstream NaCl reabsorption and attempts to maximally reduce albumin excretion. Strategies to limit albumin excretion include the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and appropriate limitation of protein intake. These measures are more logical, effective, and less expensive than infusion of albumin solutions. PMID:11856788

  16. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  17. A Novel Member of the Trehalose Transporter Family Functions as an H+-Dependent Trehalose Transporter in the Reabsorption of Trehalose in Malpighian Tubules

    PubMed Central

    Kikuta, Shingo; Hagiwara-Komoda, Yuka; Noda, Hiroaki; Kikawada, Takahiro

    2012-01-01

    In insects, Malpighian tubules are functionally analogous to mammalian kidneys in that they not only are essential to excrete waste molecules into the lumen but also are responsible for the reabsorption of indispensable molecules, such as sugars, from the lumen to the principal cells. Among sugars, the disaccharide trehalose is highly important to insects because it is the main hemolymph sugar to serve as a source of energy and carbon. The trehalose transporter TRET1 participates in the transfer of newly synthesized trehalose from the fat body across the cellular membrane into the hemolymph. Although transport proteins must play a pivotal role in the reabsorption of trehalose in Malpighian tubules, the molecular context underlying this process remains obscure. Previously, we identified a Tret1 homolog (Nlst8) that is expressed principally in the Malpighian tubules of the brown planthopper (BPH). Here, we used the Xenopus oocyte expression system to show that NlST8 exerts trehalose transport activity that is elevated under low pH conditions. These functional assays indicate that Nlst8 encodes a proton-dependent trehalose transporter (H-TRET1). To examine the involvement of Nlst8 in trehalose reabsorption, we analyzed the sugar composition of honeydew by using BPH with RNAi gene silencing. Trehalose was detected in the honeydew as waste excreted from Nlst8-dsRNA-injected BPH under hyperglycemic conditions. However, trehalose was not expelled from GFP-dsRNA-injected BPH even under hyperglycemic conditions. We conclude that NlST8 could participate in trehalose reabsorption driven by a H+ gradient from the lumen to the principal cells of the Malpighian tubules. PMID:22934042

  18. 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

  19. 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. PMID:21665585

  20. Effects of central administration of morphine on renal function in conscious rats.

    PubMed

    Danesh, S; Walker, L A

    1988-02-01

    Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism. PMID:3346840

  1. 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.

  2. Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats.

    PubMed

    Pinto, Vanda; Amaral, João; Silva, Elisabete; Simão, Sónia; Cabral, José Miguel; Afonso, Joana; Serrão, Maria Paula; Gomes, Pedro; Pinho, Maria João; Soares-da-Silva, Patrício

    2011-01-01

    This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption. PMID:21699911

  3. Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells.

    PubMed

    Ikari, Akira; Sanada, Ayumi; Sawada, Hayato; Okude, Chiaki; Tonegawa, Chie; Sugatani, Junko

    2011-06-01

    Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is used in treatments for transplantation and cancer. Rapamycin causes hypomagnesemia, although precisely how has not been examined. Here, we investigated the effect of rapamycin on the expression of transient receptor potential melastatin 6 (TRPM6), a Mg2+ channel. Rapamycin and LY-294002, an inhibitor of phosphatidilinositol-3 kinase (PI3K) located upstream of mTOR, inhibited epidermal growth factor (EGF)-induced expression of the TRPM6 protein without affecting TRPM7 expression in rat renal NRK-52E epithelial cells. Both rapamycin and LY-294002 decreased EGF-induced Mg2+ influx. U0126, a MEK inhibitor, inhibited EGF-induced increases in c-Fos, p-ERK, and TRPM6 levels. In contrast, neither rapamycin nor LY-294002 inhibited EGF-induced increases in p-ERK and c-Fos levels. EGF increased p-Akt level, an effect inhibited by LY-294002 and 1L-6-hydroxymethyl-chiro-inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate] (Akt inhibitor). Akt inhibitor decreased TRPM6 level similar to rapamycin and LY-294002. These results suggest that a PI3K/Akt/mTOR pathway is involved in the regulation of TRPM6 expression. Rapamycin inhibited the EGF-induced increase in TRPM6 mRNA but did not inhibit human TRPM6 promoter activity. In the presence of actinomycin D, a transcriptional inhibitor, rapamycin accelerated the decrease in TRPM6 mRNA. Rapamycin decreased the expression and activity of a luciferase linked with the 3'-untranslated region of human TRPM6 mRNA. These results suggest that TRPM6 expression is up-regulated by a PI3K/Akt/mTOR pathway and rapamycin reduces TRPM6 mRNA stability, resulting in a decrease in the reabsorption of Mg2+. PMID:21073857

  4. 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. PMID:26661279

  5. Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria.

    PubMed

    Seliverstova, E V; Prutskova, N P

    2015-01-01

    The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes), and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals. PMID:26150156

  6. Kappa-opioid-receptor agonists modulate the renal excretion of water and electrolytes in anaesthetized rats.

    PubMed

    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

  7. Receptor-Mediated Endocytosis of Lysozyme in Renal Proximal Tubules of the Frog Rana Temporaria

    PubMed Central

    Seliverstova, E.V.

    2015-01-01

    The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endo-somes), and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intra-cellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals. PMID:26150156

  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. 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.

  10. Interaction between the renal excretion rates of beta 2-microglobulin and tobramycin in man.

    PubMed

    Vree, T B; Zweens, K; Huige, P J; Guelen, P J; Jongman-Nix, B

    1984-03-27

    The renal excretion rate of beta 2-microglobulin in man is 127 +/- 98 ng/min at alkaline urine pH (pH 7). Tobramycin, up to intravenous doses of 160 mg (2 mg/kg) does not increase the renal excretion rate of beta 2-microglobulin. Tobramycin must have less affinity than gentamicin for the tubular system for active reabsorption of amino groups containing organic compounds. Due to this reduced affinity tobramycin will be absorbed less by the proximal tubular cells, which may be one of the reasons for tobramycin being less toxic than gentamicin. beta 2-Microglobulin excretion can be used as a parameter for the relative binding affinity of aminoglycosides. PMID:6370509

  11. Role of the Collecting Duct Renin Angiotensin System in Regulation of Blood Pressure and Renal Function.

    PubMed

    Ramkumar, Nirupama; Kohan, Donald E

    2016-04-01

    Recent evidence suggests that the renal tubular renin angiotensin system regulates urinary Na(+) and water excretion and blood pressure. Three key components of the tubular renin angiotensin system, namely renin, prorenin receptor, and angiotensin-II type 1 receptor, are localized to the collecting duct. This system may modulate collecting duct Na(+) and water reabsorption via angiotensin-II-dependent and angiotensin-II-independent pathways. Further, the system may be of greatest relevance in hypertensive states and particularly those characterized by high circulating angiotensin-II. In this review, we summarize the current knowledge on the synthesis, regulation, and function of collecting duct-derived renin angiotensin system components and examine recent developments with regard to regulation of blood pressure and renal fluid and Na(+) excretion. PMID:26951246

  12. Mineralocorticoid-induced sodium appetite and renal salt retention: evidence for common signaling and effector mechanisms.

    PubMed

    Fu, Yiling; Vallon, Volker

    2014-01-01

    An increase in renal sodium chloride (salt) retention and an increase in sodium appetite are the body's responses 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 the 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 therapeutic 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

  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. The rectal complex and Malpighian tubules of the cabbage looper (Trichoplusia ni): regional variations in Na+ and K+ transport and cation reabsorption by secondary cells.

    PubMed

    O'Donnell, Michael J; Ruiz-Sanchez, Esau

    2015-10-01

    In larvae of most Lepidoptera the distal ends of the Malpighian tubules are closely applied to the rectal epithelia and are ensheathed within the perinephric membrane, thus forming the rectal complex. The cryptonephric Malpighian tubules within the rectal complex are bathed in fluid within a functional compartment, the perinephric space, which is separate from the haemolymph. In this study, the scanning ion-selective electrode technique (SIET) was used to measure transport of Na(+) and K(+) across the rectal complex and across multiple regions of the Malpighian tubules of larvae of the cabbage looper Trichoplusia ni. Measurements were made in an intact preparation in which connections of the tubules upstream to the rectal complex and downstream to the urinary bladder and gut remained intact. SIET measurements revealed reabsorption of Na(+) and K(+) across the intact rectal complex and into the bath (haemolymph), with K(+) fluxes approximately twice as large as those of Na(+). Analyses of fluxes in larvae with empty guts, found in recently moulted larvae, versus those with full guts highlighted differences in the rates of K(+) or Na(+) transport within tubule regions that appeared morphologically homogeneous, such as the rectal lead. The distal rectal lead of larvae with empty guts reabsorbed K(+), whereas the same region secreted K(+) in tubules of larvae with full guts. SIET measurements of the ileac plexus also indicated a novel role for secondary (type II) cells in cation reabsorption. Secondary cells reabsorb K(+), whereas the adjacent principal (type I) cells secrete K(+). Na(+) is reabsorbed by both principal and secondary cells, but the rate of reabsorption by the secondary cells is approximately twice the rate in the adjacent principal cells. PMID:26491192

  15. Inherited renal cystic diseases.

    PubMed

    Kim, Bohyun; King, Bernard F; Vrtiska, Terri J; Irazabal, Maria V; Torres, Vicente E; Harris, Peter C

    2016-06-01

    A number of inherited renal diseases present with renal cysts and often lead to end-stage renal disease. With recent advances in genetics, increasing number of genes and mutations have been associated with cystic renal diseases. Although genetic testing can provide a definite diagnosis, it is often reserved for equivocal cases or for ongoing investigational research. Therefore, imaging findings are essential in the routine diagnosis, follow-up, and detection of complications in patients with inherited cystic renal diseases. In this article, the most recent classification, genetic analysis, clinical presentations, and imaging findings of inherited cystic renal diseases will be discussed. PMID:27167233

  16. 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

    2016-01-01

    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

  17. 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

  18. Renal cell cancer and exposure to gasoline: a review.

    PubMed Central

    McLaughlin, J K

    1993-01-01

    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. PMID:8020434

  19. 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 Update Date 5/19/2015 Updated by: ...

  20. Kidney (Renal) Failure

    MedlinePlus

    ... renal function using ureteral stenting, nephrostomy, surgery or dialysis. What is kidney (renal) failure? How is kidney ... as a urinary stent or kidney stone removal. Dialysis , including hemodialysis and peritoneal dialysis: These procedures remove ...

  1. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  2. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  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.

  4. 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

  5. [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. PMID

  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. 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.

  8. 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.

  9. Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure.

    PubMed

    Zhou, Xiaoyan; Zhang, Zuo; Shin, Myung Kyun; Horwitz, Sarah Beth; Levorse, John M; Zhu, Lei; Sharif-Rodriguez, Wanda; Streltsov, Denis Y; Dajee, Maya; Hernandez, Melba; Pan, Yi; Urosevic-Price, Olga; Wang, Li; Forrest, Gail; Szeto, Daphne; Zhu, Yonghua; Cui, Yan; Michael, Bindhu; Balogh, Leslie Ann; Welling, Paul A; Wade, James B; Roy, Sophie; Sullivan, Kathleen A

    2013-08-01

    The renal outer medullary potassium channel (ROMK, KCNJ1) mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK(-/-) pups recapitulated features identified in the ROMK null mice. The ROMK(+/-) rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK(+/+) littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation. PMID:23753405

  10. 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.

  11. Effect of renal denervation on the antinatriuretic response to morphine administration in conscious rats.

    PubMed

    Walker, L A; Murphy, J C

    1986-06-01

    The effect of surgical denervation on the antinatriuretic response to morphine was assessed in conscious rats prepared with arterial and venous catheters and bladder cannulas. In sham-operated animals, morphine sulfate (4 mg/kg i.v. plus 2 mg/kg X hr) caused a marked reduction in sodium excretion (650 +/- 218 vs. 2394 +/- 265 nEq/100 g X min in vehicle-treated animals; P less than .05). Although glomerular filtration rate was reduced, fractional excretion of sodium, expressed as a percentage of the filtered load, was also markedly decreased by morphine (0.62 +/- 0.18 vs. 1.51 +/- 0.15% in the vehicle group; P less than .05). The changes in sodium excretion were readily reversed by naloxone. In rats subjected to the renal denervation procedure, morphine had no effect on sodium excretion (1614 +/- 261 vs. 1926 +/- 520 nEq/100 g X min) or on fractional sodium excretion (1.92 +/- 0.50 vs. 1.41 +/- 0.37%). However, glomerular filtration rate was reduced by morphine as in the sham-denervated rats. Blood pressure and heart rate were not significantly affected by morphine in either group. The results suggest that morphine enhances renal tubular sodium reabsorption, at least in part, by a mechanism dependent on intact renal nerves. Because there was no evidence of generalized sympathetic activation (as judged by blood pressure and heart rate changes), the effect may be selective for the renal innervation. PMID:3712279

  12. Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds.

    PubMed

    Du, Chan; Narayanan, Karthikeyan; Leong, Meng Fatt; Ibrahim, Mohammed Shahrudin; Chua, Ying Ping; Khoo, Vanessa Mei Hui; Wan, Andrew C A

    2016-08-01

    Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney. PMID:27294565

  13. Localization of corin and atrial natriuretic peptide expression in human renal segments.

    PubMed

    Dong, Liang; Wang, Hao; Dong, Ningzheng; Zhang, Ce; Xue, Boxin; Wu, Qingyu

    2016-09-01

    Atrial natriuretic peptide (ANP)-mediated natriuretic response is a well-established cardiac endocrine function. Corin is a transmembrane protease that activates ANP in the heart. Corin expression has been detected in non-cardiac tissues including the kidney. Here we examined corin, pro-ANP/ANP and natriuretic peptide receptor-A (NPR-A) expression in human renal segments. By immunostaining and in situ hybridization, we found similar corin, pro-ANP/ANP and NPR-A protein and mRNA expression in human renal segments. The expression was most abundant in the proximal convoluted tubules and the medullary connecting ducts. In the proximal tubules, corin protein was present in the apical membrane region underneath the brush border where the ANP-degrading protease neprilysin was abundant. These results suggest that corin-mediated pro-ANP activation may occur in renal segments and that locally produced ANP may act in an autocrine manner to regulate sodium and water reabsorption in situ Our results also point to the proximal convoluted tubules as a major site for local ANP action. Such a renal corin/ANP autocrine mechanism may differ from the cardiac corin/ANP endocrine mechanism in regulating sodium homoeostasis under physiological and pathological conditions. PMID:27343265

  14. Effect of Chronic Bile Duct Obstruction on Renal Handling of Salt and Water

    PubMed Central

    Better, Ori S.; Massry, Shaul G.

    1972-01-01

    Renal sodium reabsorption and the concentrating and diluting abilities of the kidney were evaluated in the same trained mongrel dogs before and after chronic common bile duct ligation (BDL). Glomerular filtration rate (GFR) and CPAH were not altered by BDL. The natriuretic response to a standardized infusion of 0.45% solution of NaCl was markedly blunted by BDL (P < 0.01); calculated distal sodium delivery was significantly less in experiments after BDL than in control studies. Furthermore, the fractional reabsorption of sodium at the diluting segment for any given rate of distal delivery was enhanced by BDL. Similarly, CH2O/100 ml GFR for a given sodium delivery was higher after BDL than control values. Maximal urinary concentration (Uosm-max) was lower after BDL, and the mean Uosm-max for the whole group of animals was 60% of the control value (P < 0.001). Mean maximal TH2O/100 ml GFR after BDL was not different from control values; however, TcH2O/100 ml GFR for a given Cosm/100 ml GFR was lower after BDL in three dogs only. The sodium content of the inner part of renal medulla after BDL was significantly lower than the values obtained in control animals. The excretion of an oral water load in the conscious state was impaired after BDL; although all animals excreted hypotonic urine, urinary osmolality was usually higher after BDL than in control studies. Maximal urinary concentration and the excretion of an oral water load were not affected by sham operation. These studies demonstrate that chronic, common bile duct ligation is associated with (a) enhanced sodium reabsorption both in the proximal and diluting segments of the nephron, (b) a defect in attaining maximal urinary concentration, (c) diminished sodium content in the renal papilla, and (d) impaired excretion of a water load. The results suggest that decreased distal delivery of sodium may underlie the abnormality in the concentrating mechanism and in the inability to normally excrete a water load. In

  15. [New perspective on the role of WNK1 and WNK4 in the regulation of NaCl reabsorption and K(+) secretion by the distal nephron].

    PubMed

    Rafael, Chloé; Chavez-Canales, Maria; Hadchouel, Juliette

    2016-03-01

    The study of Familial Hyperkalemic Hypertension (FHHt), a rare monogenic disease, allowed remarkable advances in the understanding of the mechanisms of regulation of NaCl reabsorption by the distal nephron. FHHt results from mutations in the genes encoding WNK1 and WNK4, two serine-threonine kinases of the WNK (With No lysine [K]) family. The clinical manifestations of FHHt are due, among others, to an increased activity of the Na(+)-Cl(-) cotransporter NCC. Several groups therefore tried to understand how WNK1 and WNK4 could regulate NCC. However, the data were often contradictory. Two of our recent studies allowed to partially explain these controversies and to propose a new model for the regulation of NCC by the WNKs. PMID:27011246

  16. 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

  17. Renal cystic disease

    SciTech Connect

    Hartman, D.S.

    1988-01-01

    The book begins with an overview of renal cystic disease and a presentation of simple renal cysts. Subsequent chapters cover cystic disease in association with renal neoplasms and medullary sponge kidney. The chapters addressing autosomal-dominant and autosomal-recessive polycystic kidney disease discuss and differentiate the infantile and adult forms of the disease. There are also separate discussions of medullary cystic disease, multicystic dysplastic kidney, and cysts of the renarenal sinus.

  18. Calcified renal oncocytoma

    SciTech Connect

    Wasserman, N.F.; Ewing, S.L.

    1983-10-01

    Renal oncocytoma, a neoplasm thought to derive from cells of the proximal convoluted tubules, exhibits benign clinical features. Its preoperative distinction from typical renal cell carcinoma would enable the surgeon to perform a more limited procedure. In a patient who is a poor operative candidate, surgery might be deferred. However, preoperative diagnosis has been elusive. A rare case of bilateral renal oncocytoma is reported. One of these tumors represents the first reported oncocytoma showing radiologically demonstrable calcification.

  19. [Hereditary renal cell carcinomas].

    PubMed

    Hartmann, A; Stöhr, C G; Junker, K

    2010-10-01

    Renal cell carcinomas occur in several hereditary tumor syndromes. These renal tumors frequently have a specific histopathological appearance which can be a sign for a hereditary cause of the disease. The genetic alterations responsible for most of these tumor syndromes were identified in recent years. Interestingly, renal cell carcinomas show specific histopathological features in each of the hereditary renal cancer syndromes. Clear cell and often cystic renal cell carcinomas occur in von Hippel-Lindau syndrome (VHL), while oncocytomas and chromophobe renal cell carcinomas are found in the Birt-Hugg-Dube syndrome, often also as hybrid tumors. Well differentiated papillary carcinomas (Type 1 according to the WHO) are found in the hereditary papillary renal cell carcinoma (HPRC). In contrast, poorly diffentiated papillary renal cell carcinomas (Type 2 according to the WHO) occur in combination with leiomyomas and leiomyosarcomas of the skin and uterus in hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The various genetic causes for these hereditary tumor syndromes open up new therapeutic possibilities, some of which are already being investigated in clinical studies. PMID:20960197

  20. Segmental neurofibromatosis associated with renal angiomyolipomas.

    PubMed

    Nguyen, Kim-Tan; Chiu, Melvin

    2008-07-01

    Segmental neurofibromatosis (SN) is a rare disorder characterized by neurofibromas or neurofibromas with café-au-lait spots limited to one region of the body without crossing the midline. Renal angiomyolipomas (AMLs) are rare benign neoplasms usually found in association with tuberous sclerosis (TS). Similar to neurofibromatosis (NF), TS has a high spontaneous mutation rate and a family history often is absent. Although both are autosomal dominant diseases with neural involvement, there are few reports in the literature demonstrating a link between the 2 disorders. We report a case of SN associated with renal AMLs. To our knowledge, there has been only 1 prior report of renal AML associated with NF type 1 (NF1), and there have been no prior reports of SN associated with AML. PMID:18712027

  1. Tuberous Sclerosis Complex Renal Disease

    PubMed Central

    Dixon, Bradley P.; Hulbert, John C.; Bissler, John J.

    2010-01-01

    Although not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease. PMID:21071977

  2. Laboratory Markers of Ventricular Arrhythmia Risk in Renal Failure

    PubMed Central

    2014-01-01

    Sudden cardiac death continues to be a major public health problem. Ventricular arrhythmia is a main cause of sudden cardiac death. The present review addresses the links between renal function tests, several laboratory markers, and ventricular arrhythmia risk in patients with renal disease, undergoing or not hemodialysis or renal transplant, focusing on recent clinical studies. Therapy of hypokalemia, hypocalcemia, and hypomagnesemia should be an emergency and performed simultaneously under electrocardiographic monitoring in patients with renal failure. Serum phosphates and iron, PTH level, renal function, hemoglobin and hematocrit, pH, inflammatory markers, proteinuria and microalbuminuria, and osmolarity should be monitored, besides standard 12-lead ECG, in order to prevent ventricular arrhythmia and sudden cardiac death. PMID:24982887

  3. Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases γ-Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study

    PubMed Central

    Morris, Marilyn E.; Morse, Bridget L.; Baciewicz, Gloria J.; Tessena, Matthew M.; Acquisto, Nicole M.; Hutchinson, David J.; DiCenzo, Robert

    2012-01-01

    Background and objective The purpose of the current study was to demonstrate proof-of-concept that monocarboxylate transporter (MCT) inhibition with L-lactate combined with osmotic diuresis increases renal clearance of γ-hydroxybutyrate (GHB) in human subjects. GHB is a substrate for human and rodent MCTs, which are responsible for GHB renal reabsorption, and this therapy increases GHB renal clearance in rats. Methods Ten healthy volunteers were administered GHB orally as sodium oxybate 50 mg/kg (4.5 gm maximum dose) on two different study days. On study day 1, GHB was administered alone. On study day 2, treatment of L-lactate 0.125 mmol/kg and mannitol 200 mg/kg followed by L-lactate 0.75 mmol/kg/hr was administered intravenously 30 minutes after GHB ingestion. Blood and urine were collected for 6 hours, analyzed for GHB, and pharmacokinetic and statistical analyses performed. Results L-lactate/mannitol administration significantly increased GHB renal clearance compared to GHB alone, 439 vs. 615 mL/hr (P=0.001), and increased the percentage of GHB dose excreted in the urine, 2.2 vs. 3.3% (P=0.021). Total clearance was unchanged. Conclusions MCT inhibition with L-lactate combined with osmotic diuresis increases GHB renal elimination in humans. No effect on total clearance was observed in this study due to the negligible contribution of renal clearance to total clearance at this low GHB dose. Considering the nonlinear renal elimination of GHB, further research in overdose cases is warranted to assess the efficacy of this treatment strategy for increasing renal and total clearance at high GHB doses. PMID:24772380

  4. Renal Fanconi Syndrome Is Caused by a Mistargeting-Based Mitochondriopathy.

    PubMed

    Assmann, Nadine; Dettmer, Katja; Simbuerger, Johann M B; Broeker, Carsten; Nuernberger, Nadine; Renner, Kathrin; Courtneidge, Holly; Klootwijk, Enriko D; Duerkop, Axel; Hall, Andrew; Kleta, Robert; Oefner, Peter J; Reichold, Markus; Reinders, Joerg

    2016-05-17

    We recently reported an autosomal dominant form of renal Fanconi syndrome caused by a missense mutation in the third codon of the peroxisomal protein EHHADH. The mutation mistargets EHHADH to mitochondria, thereby impairing mitochondrial energy production and, consequently, reabsorption of electrolytes and low-molecular-weight nutrients in the proximal tubule. Here, we further elucidate the molecular mechanism underlying this pathology. We find that mutated EHHADH is incorporated into mitochondrial trifunctional protein (MTP), thereby disturbing β-oxidation of long-chain fatty acids. The resulting MTP deficiency leads to a characteristic accumulation of hydroxyacyl- and acylcarnitines. Mutated EHHADH also limits respiratory complex I and corresponding supercomplex formation, leading to decreases in oxidative phosphorylation capacity, mitochondrial membrane potential maintenance, and ATP generation. Activity of the Na(+)/K(+)-ATPase is thereby diminished, ultimately decreasing the transport activity of the proximal tubule cells. PMID:27160910

  5. Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions.

    PubMed

    Kalra, Jaspreet; Prakash, Atish; Kumar, Puneet; Majeed, Abu Bakar Abdul

    2015-09-01

    Work on the brain renin-angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed. PMID:25944853

  6. Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism.

    PubMed

    Glahn, R P; Beers, K W; Bottje, W G; Wideman, R F; Huff, W E; Thomas, W

    1991-11-01

    Experiments were designed to determine the effects of aflatoxicosis on avian renal function, calcium (CA), inorganic phosphorous (Pi), and vitamin D metabolism, and to determine if the effects of aflatoxin are reversible upon discontinuation of toxin administration. Three-week-old male broiler chickens (n = 12 per treatment) received aflatoxin (AF; 2 mg/kg po) or an equal volume of corn oil, the AF carrier vehicle, for 10 consecutive days. After 10 d of treatment, half of the birds from each treatment group were anesthetized and prepared for renal function analysis, which included a 2-h phosphate loading period. Ten days after discontinuation of AF treatment, the remaining birds in each treatment group were anesthetized and prepared for renal function analysis. AF decreased plasma 25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D] levels after 5 d of treatment. After 10 d of treatment, urine flow rate (V), fractional sodium excretion (FENa), and fractional potassium excretion (FEK) were lower in AF-treated birds. In addition, total plasma Ca tended to be lower (p = .10) and fractional Ca excretion (FECa) tended to be higher (p = .10) in the AF-treated birds. Intravenous phosphate loading produced a sharp increase in urine hydrogen ion concentration ([H+]) in the AF-treated birds. Glomerular filtration rate (GFR) was reduced and plasma osmolality was increased in AF-treated birds 10 d after discontinuation of toxin administration. The results indicate that AF directly or indirectly affects Ca and Pi metabolism in avians. At the present time, the effects may be related to altered vitamin D and parathyroid hormone (PTH) metabolism. Aflatoxicosis may decrease endogenous PTH synthesis and the renal sensitivity to PTH. The AF-related increase in urine [H+] during phosphate loading is probably due to increased Na+/H+ counterport, suggesting that AF stimulates sodium reabsorption. Also, the decrease in GFR exhibited 10 d after toxin removal indicates

  7. Urinary and proximal tubule acidification during reduction of renal blood flow in the rat.

    PubMed Central

    Jaramillo-Juárez, F; Aires, M M; Malnic, G

    1990-01-01

    1. The effects of reduction in renal blood flow (RBF) on urinary acidification and proximal tubule H+ ion secretion were studied after partial aortic clamping in rats. 2. Acute reduction of the renal perfusion pressure (from 109 +/- 3.88 to 77.4 +/- 1.05 mmHg) decreased both inulin and PAH (p-aminohippurate) clearances to about one-third of their control values. Absolute levels of urinary sodium excretion also decreased markedly, but fractional sodium excretion did not change significantly. 3. Urine pH and bicarbonate levels were not affected, but titratable acidity increased significantly from 0.12 +/- 0.011 to 0.25 +/- 0.042 muequiv min-1 ml-1 glomerular filtration rate (GFR). During aortic clamping, cortical PCO2 as determined by means of Severinghaus microelectrodes was reduced by a mean value of 7.0 +/- 1.5 mmHg. 4. Proximal tubule acidification kinetics were studied by stationary microperfusion techniques in which the time course of pH changes was monitored by pH microelectrodes. Steady-state pH fell from a mean control value of 6.77 +/- 0.03 to 6.65 +/- 0.02, and stationary bicarbonate concentrations from 4.70 +/- 0.27 to 2.84 +/- 0.18 mM. Acidification half-time decreased from 5.07 +/- 0.30 to 4.39 +/- 0.19 s, and net bicarbonate reabsorption increased from 1.63 +/- 0.14 to 1.99 +/- 0.12 nmol cm-2 s-1, these changes being statistically significant. 5. The experiments demonstrate that both overall acid excretion and proximal acid secretion are not compromised by a large decrease of RBF to about one-third of the control value; titratable acid excretion and proximal net bicarbonate reabsorption were even moderately increased under these conditions. PMID:2348400

  8. Fructokinase activity mediates dehydration-induced renal injury.

    PubMed

    Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

    2014-08-01

    The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy. PMID:24336030

  9. [Atherosclerotic renal artery stenosis].

    PubMed

    Sauguet, A; Honton, B

    2014-12-01

    Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension. PMID:25450992

  10. Cadmium and renal cancer

    SciTech Connect

    Il'yasova, Dora; Schwartz, Gary G. . E-mail: gschwart@wfubmc.edu

    2005-09-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine.

  11. Mitochondrial and Metabolic Dysfunction in Renal Convoluted Tubules of Obese Mice: Protective Role of Melatonin

    PubMed Central

    Giugno, Lorena; Lavazza, Antonio; Reiter, Russel J.; Rodella, Luigi Fabrizio; Rezzani, Rita

    2014-01-01

    Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, which are the major tubules involved in reabsorptive processes. For optimal performance of the kidney, energy is primarily provided by mitochondria. Melatonin, an indoleamine and antioxidant, has been identified in mitochondria, and there is considerable evidence regarding its essential role in the prevention of oxidative mitochondrial damage. In this study we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondrial morphology and dynamics as influenced by mitofusin-2 and the intrinsic apoptotic cascade. Melatonin dissolved in 1% ethanol was added to the drinking water from postnatal week 5–13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-related morphological alterations were apparent in the proximal tubules which contained round mitochondria with irregular, short cristae and cells with elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria-driven intrinsic apoptotic pathway. These changes possibly aid in reducing renal failure. The melatonin-mediated changes indicate its potential protective use against renal morphological damage and dysfunction associated with obesity and metabolic disease. PMID:25347680

  12. Purification and renal effects of phospholipase A(2) isolated from Bothrops insularis venom.

    PubMed

    Machado Braga, Marcus Davis; Costa Martins, Alice Maria; Alves, Claudênio Diógenes; de Menezes, Dalgimar Beserra; Martins, René Duarte; Ferreira Barbosa, Paulo Sérgio; de Sousa Oliveira, Isadora Maria; Toyama, Marcos Hikari; Toyama, Daniela Oliveira; Dos Santos Diz Filho, Eduardo Brito; Ramos Fagundes, Fabio Henrique; Fonteles, Manassés Claudino; Azul Monteiro, Helena Serra

    2008-02-01

    Bothrops insularis venom contains a variety of substances presumably responsible for several pharmacological effects. We investigated the biochemical and biological effects of phospholipase A(2) protein isolated from B. insularis venom and the chromatographic profile showed 7 main fractions and the main phospholipase A(2) (PLA(2)) enzymatic activity was detected in fractions IV and V. Fraction IV was submitted to a new chromatographic procedure on ion exchange chromatography, which allowed the elution of 5 main fractions designated as IV-1 to IV-5, from which IV-4 constituted the main fraction. The molecular homogeneity of this fraction was characterized by high-performance liquid chromatography (HPLC) and demonstrated by mass spectrometry (MS), which showed a molecular mass of 13984.20 Da; its N-terminal sequence presented a high amino acid identity (up to 95%) with the PLA(2) of Bothrops jararaca and Bothrops asper. Phospholipase A(2) isolated from B. insularis (Bi PLA(2) ) venom (10 microg/mL) was also studied as to its effect on the renal function of isolated perfused kidneys of Wistar rats (n=6). Bi PLA(2) increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa(+)) and chloride tubular reabsorption (%TCl(-)) decreased at 120 min, without alteration in potassium transport. In conclusion, PLA(2) isolated from B. insularis venom promoted renal alterations in the isolated perfused rat kidney. PMID:17953979

  13. NHERF-1 and the regulation of renal phosphate reabsoption: a tale of three hormones

    PubMed Central

    Lederer, Eleanor D.

    2012-01-01

    The renal excretion of inorganic phosphate is regulated in large measure by three hormones, namely, parathyroid hormone, dopamine, and fibroblast growth factor-23. Recent experiments have indicated that the major sodium-dependent phosphate transporter in the renal proximal tubule, Npt2a, binds to the adaptor protein sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and in the absence of NHERF-1, the inhibitory effect of these three hormones is absent. From these observations, a new model for the hormonal regulation of renal phosphate transport was developed. The downstream signaling pathways of these hormones results in the phosphorylation of the PDZ 1 domain of NHERF-1 and the dissociation of Npt2a/NHERF-1 complexes. In turn, this dissociation facilitates the endocytosis of Npt2a with a subsequent decrease in the apical membrane abundance of the transporter and a decrease in phosphate reabsorption. The current review outlines the experimental observations supporting the operation of this unique regulatory system. PMID:22535796

  14. Multicystic renal dysplasia.

    PubMed

    Nagaraj, V P; Ratnakar, K S

    2001-07-01

    Multicystic renal dysplasia, the most common form of cystic renal disease in the newborn period, is a clinically important consequence of abnormal nephrogenesis. It usually presents as an abdominal mass. The dysplasias are usually unilateral, but it can be bilateral, segmental or focal. The clinical presentation usually depends on the extent of the dysplastic involvement and the degree of the associated urinary obstruction. Here, we present a case of histologically multicystic renal dysplasia, which is ?bilateral. The left kidney showed typical radiological, gross and histopathological features of multicystic dysplasia, but the right kidney showed only radiological features of dysplastic cystic kidney. PMID:11479648

  15. Renal Replacement Therapy.

    PubMed

    Villa, Gianluca; Ricci, Zaccaria; Ronco, Claudio

    2015-10-01

    Renal replacement therapy (RRT) is a cornerstone in the clinical management of patients with acute kidney injury. Results from different studies agree that early renal support therapy (aimed to support the residual kidney function during early phases of organ dysfunction) may reduce mortality with respect to late RRT (aimed to substitute the complete loss of function during the advanced kidney insufficiency). Although it seems plausible that a timely initiation of RRT may be associated with improved renal and nonrenal outcomes in these patients, there is scarce evidence in literature to exactly identify the most adequate onset timing for RRT. PMID:26410148

  16. Idiopathic hypercalciuria and formation of calcium renal stones.

    PubMed

    Coe, Fredric L; Worcester, Elaine M; Evan, Andrew P

    2016-09-01

    The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall's plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone disease. PMID:27452364

  17. Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells.

    PubMed

    Mitsuoka, Keisuke; Shirasaka, Yoshiyuki; Fukushi, Akimasa; Sato, Masanobu; Nakamura, Toshimichi; Nakanishi, Takeo; Tamai, Ikumi

    2009-04-01

    L-Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L-citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L-citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L-Citrulline was transported in a Na(+)-dependent manner from the apical side of both cell types cultured on permeable supports with a microporous membrane. Kinetic analysis indicated that the transport involves two distinct Na(+)-dependent saturable systems and one Na(+)-independent saturable system in HK-2 cells. The uptake was competitively inhibited by neutral and cationic, but not anionic amino acids. Relatively large cationic and anionic compounds inhibited the uptake, but smaller ones did not. In HK-2 cells, mRNA expression of SLC6A19 and SLC7A9, which encode B(0)AT1 and b(0,+)AT, respectively, was detected by RT-PCR. In addition, L-citrulline transport was significantly decreased in HK-2 cells in which either SLC6A19 or SLC7A9 was silenced. Hence, these results suggest that amino acid transporters B(0)AT1 and b(0,+)AT are involved in the reabsorption of L-citrulline in the kidney, at least in part, by mediating the apical membrane transport of L-citrulline in renal tubule cells. PMID:19322909

  18. Renal Mitochondrial Cytopathies

    PubMed Central

    Emma, Francesco; Montini, Giovanni; Salviati, Leonardo; Dionisi-Vici, Carlo

    2011-01-01

    Renal diseases in mitochondrial cytopathies are a group of rare diseases that are characterized by frequent multisystemic involvement and extreme variability of phenotype. Most frequently patients present a tubular defect that is consistent with complete De Toni-Debré-Fanconi syndrome in most severe forms. More rarely, patients present with chronic tubulointerstitial nephritis, cystic renal diseases, or primary glomerular involvement. In recent years, two clearly defined entities, namely 3243 A > G tRNALEU mutations and coenzyme Q10 biosynthesis defects, have been described. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this paper, the physiopathologic bases of mitochondrial cytopathies, the diagnostic approaches, and main characteristics of related renal diseases are summarized. PMID:21811680

  19. 'Transcollateral' Renal Angioplasty for a Completely Occluded Renal Artery

    SciTech Connect

    Chandra, Subash; Chadha, Davinder S. Swamy, Ajay

    2011-02-15

    Percutaneous transluminal renal angioplasty with stenting has been effective in the control of hypertension, renal function, and pulmonary edema caused by atherosclerotic renal artery stenosis. However, the role of the procedure has not been fully established in the context of chronic total occlusion of renal artery. We report the successful use of this procedure in 57-year-old male patient who reported for evaluation of a recent episode of accelerated hypertension. A renal angiogram in this patient showed ostial stenosis of the right renal artery, which was filling by way of the collateral artery. Renal angioplasty for chronic total occlusion of right renal artery was successfully performed in a retrograde fashion through a collateral artery, thereby leading to improvement of renal function and blood pressure control.

  20. Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule.

    PubMed

    Pessoa, Thaissa Dantas; Campos, Luciene Cristina Gastalho; Carraro-Lacroix, Luciene; Girardi, Adriana C C; Malnic, Gerhard

    2014-09-01

    Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule. PMID:24652792

  1. [Renal function, organic acid transport and protein binding: the three elements defining the response to diuretics in clinical practice: an update].

    PubMed

    Conz, P A

    2005-01-01

    Organic anion transporters (OATs), which are expressed in proximal tubule cells, mediate diuretic secretion into tubular fluid. Increased plasma levels of organic anions and urate and metabolic acidosis, i.e. two characteristic features of chronic renal insufficiency, could be factors contributing to diuretic resistance. These limitations demand increasing doses of diuretics up to a maximum level, or the use of a loop diuretic with non-renal metabolism. Diuretic responsiveness in nephrotic syndrome is limited by strong Na+ reabsorption in the distal nephron. Strategies to improve loop diuretic responsiveness include diuretic dosage and the combination of a loop diuretic with a distal acting diuretic. Strategies to limit protein excretion include the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and appropriate salt intake limitation. PMID:16001364

  2. Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease.

    PubMed

    Chang, H-H; Chao, H-N; Walker, C S; Choong, S-Y; Phillips, A; Loomes, K M

    2015-11-01

    Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease. PMID:26311112

  3. Disappearing renal calculus

    PubMed Central

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-01-01

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging. PMID:23580676

  4. Hereditary Renal Cancer Syndromes

    PubMed Central

    Haas, Naomi B.

    2013-01-01

    Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of renal cancer, which are reviewed herein. Clear cell renal cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome and mutations in BAP1, as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary renal cancers arise in conjunction with germline mutations in MET and type 2 as part of Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations). Chromophone and oncocytic renal cancers are predominantly associated with Birt Hogg Dubé syndrome. Angiomyolipomas are commonly and their malignant counterpart epitheliod angiomyolipomas rarely are found in patients with Tuberous Sclerosis Complex. The targeted therapeutic options for the renal cancer associated with these diseases are just starting to expand, and are an area of active clinical research. PMID:24359990

  5. Renal Proteome in Mice with Different Susceptibilities to Fluorosis

    PubMed Central

    Peres-Buzalaf, Camila; Salvato, Fernanda; Labate, Carlos Alberto; Everett, Eric T.; Whitford, Gary Milton; Buzalaf, Marília Afonso Rabelo

    2013-01-01

    A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F) metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18) and 129P3/J mice (resistant, n = 18) were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies. PMID:23308176

  6. [Hereditary renal cancer].

    PubMed

    Sanz-Ortega, Julián; Olivier, Carlos; Pérez Segura, Pedro; Galante Romo, Isabel; San José Mansó, Luis; Saez, Mamen

    2009-02-01

    Kidney cancer is the tenth most common cause of cancer death. There are a growing number of genes known to be associated with an increased risk of specific types of kidney cancer. People with Von Hippel-Lindau syndrome have about a 40% risk of developing multiple bilateral clear cell kidney cancers. They can also develop retinal and brain hemangioblastoma, kidneys or pancreas cysts, pheochromocytoma and endolymphatic sac tumor. Four phenotypes with different renal cancer and pheocromocitoma risk have been described depending on the germline mutation. Hereditary papillary renal cell carcinoma syndrome has type 1 papillary renal cell carcinomas associated with protooncogene c-MET germline mutations. Birt-Hogg-Dubé syndrome has FLCN gene mutations associated with fibrofolliculomas, lung cysts with a high risk for spontaneous pneumothorax, and a 15% to 30% risk of kidney cancer (most classified as chromophobe carcinoma, oncocytoma or oncocytic hybrid, but clear cell and papillary kidney cancers have also been reported). Histopathological findings such as oncocytosis and oncocytic hybrids are very unusual outside the syndrome. Hereditary leiomyomatosis and renal cell cancer syndrome shows mutations of Fumarate hydratase gene and cutaneous leiomyomata in 76% of affected individuals, uterine leiomyomata in 100% of females, and unilateral, solitary, and aggressive papillary renal cancer in 10 to 16% of patients. A specific histopathological change is eosinophilic prominent nucleoli with a perinucleolar halo. Tuberous sclerosis complex is one of the most prevalent (1/5.800) hereditary syndromes where renal disease is the second leading cause of death, associated with angiomyolipomas (70%), renal cysts, oncocytomas or clear cell cancer. PMID:19418834

  7. Pharmacokinetics in renal disease.

    PubMed

    Levy, G

    1977-04-01

    The physiologic perturbations associated with renal disease can have a pronounced effect on the kinetics of elimination of drugs and their metabolites from the body. Drugs are ordinarily cleared from the body by a number of routes, each of which can be characterized by a clearance value. The sum of these clearances (renal, hepatic, etc.) is the total or body clearance which is inversely proportional to the steady-state plasma concentration produced by a given drug dosage regimen. The quantitative contribution of each route of elimination to the metabolic fate of a drug is proportional to the clearance value of that route relative to the body clearance. As a first approximation, the reduction in the renal clearance of a drug caused by renal disease is proportional to the reduction in the renal clearance of creatinine. The metabolic (biotransformation) clearance of many extensively plasma protein bound drugs is proportional to their free fraction (ratio of concentrations of free to total drug) in plasma. Since severe renal disease causes a reduction in the plasma protein binding of many drugs, the metabolic clearance of such drugs will be increased. The contribution of hemodialysis to the total clearance of a drug depends on the magnitude of the clearance obtained by hemodialysis relative to the magnitude of the body clearance of the drug on a day between dialyses. To compensate for the increased elimination of a drug during hemodialysis, the dosing rate (i.e., the dose per unit of time) must be increased by the factor (hemodialysis clearance and body clearance):body clearance, where body clearance is that during a day between dialyses. Further dosage compensation may be needed if body clearance is increased during hemodialysis due to decreased plasma protein binding of the drug. Under certain conditions, an increased accumulation of pharmacologically active drug metabolites during renal failure becomes a matter of serious concern. PMID:851113

  8. Renal haemodynamic and excretory responses to bradykinin in anaesthetized dogs.

    PubMed

    Matsumura, Y; Tadano, K; Yamasaki, T

    1999-08-01

    1. Effects of bradykinin (BK) on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Renal arterial infusion of BK at doses of 5 or 50 ng/kg per min produced dose-dependent increases in renal blood flow (RBF), without affecting systemic arterial pressure or glomerular filtration rate. There were also significant and dose-dependent increases in urine flow (UF), urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) and decreases in urine osmolality during BK infusion. 3. Renal haemodynamic and excretory responses to the BK infusion were completely abolished by the simultaneous administration of Hoe 140 (icatibant, 100 ng/kg per min intrarenally), a selective BK B2-receptor antagonist. 4. In the presence of NG-nitro-L-arginine (NOARG; 40 micrograms/kg per min intrarenally), a nitric oxide (NO) synthase inhibitor, BK-induced renal vasodilative and natriuretic effects were markedly attenuated, although responses of UF and urine osmolality to BK remained unchanged. The water diuretic effect of BK was abolished in dogs given both NOARG and ibuprofen (12.5 mg/kg bolus injection plus 12.5 mg/kg per h of sustained infusion intravenously), a cyclooxygenase inhibitor. 5. These results clearly indicate that renal haemodynamic and excretory responses to BK were mediated exclusively by the B2-receptor. Renal vasodilative and natriuretic responses are mainly linked to NO generation, while both NO and prostaglandin biosynthesis are involved in the BK-induced water diuresis. PMID:10474781

  9. p66Shc regulates renal vascular tone in hypertension-induced nephropathy.

    PubMed

    Miller, Bradley; Palygin, Oleg; Rufanova, Victoriya A; Chong, Andrew; Lazar, Jozef; Jacob, Howard J; Mattson, David; Roman, Richard J; Williams, Jan M; Cowley, Allen W; Geurts, Aron M; Staruschenko, Alexander; Imig, John D; Sorokin, Andrey

    2016-07-01

    Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy. PMID:27270176

  10. Chemokines as Potential Markers in Pediatric Renal Diseases

    PubMed Central

    Simões e Silva, Ana Cristina; Pereira, André Barreto; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio

    2014-01-01

    Glomerular diseases and obstructive uropathies are the two most frequent causes of chronic kidney disease (CKD) in children. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric renal diseases. Among several putative biomarkers, chemokines emerge as promising molecules since they play relevant roles in the pathophysiology of pediatric renal diseases. The evaluation of these inflammatory mediators might help in the management of diverse renal diseases in children and the detection of patients at high risk to develop CKD. The aim of this paper is to revise general aspects of chemokines and the potential link between chemokines and the most common pediatric renal diseases by including experimental and clinical evidence. PMID:24692841

  11. Renal disease in Colombia.

    PubMed

    Gómez, Rafael Alberto

    2006-01-01

    Chronic renal disease represents a problem of public health in Colombia. Its prevalence has increased in last decade, with a prevalence of 44.7 patients per million (ppm) in 1993 to 294.6 ppm in 2004, considering that only 56.2% of the population has access to the health. This increase complies with the implementation of Law 100 of 1993, offering greater coverage of health services to the Colombian population. The cost of these pathologies is equivalent to the 2.49% of the budget for health of the nation. The three most common causes of renal failure are diabetes mellitus (DM; 30%), arterial hypertension (30%), and glomerulonephritis (7.85%). In incident patients, the DM accounts for 32.9%. The rate of global mortality is 15.8%, 17.4% in hemodialysis and 15.1% in peritoneal dialysis. In 2004, 467 renal transplants were made, 381 of deceased donor with an incidence of 10.3 ppm. The excessive cost of these pathologies can cause the nation's health care system to collapse if preventative steps are not taken. In December of 2004, the Colombian Association of Nephrology with the participation of the Latin American Society of Nephrology and Arterial Hypertension wrote the "Declaration of Bogotá," committing the state's scientific societies and promotional health companies to develop a model of attention for renal health that, in addition to implementing national registries, continues to manage renal disease. PMID:17162422

  12. Role of renal medullary oxidative and/or carbonyl stress in salt-sensitive hypertension and diabetes.

    PubMed

    Mori, Takefumi; Ogawa, Susumu; Cowely, Allen W; Ito, Sadayoshi

    2012-01-01

    1. Salt-sensitive hypertension is commonly associated with diabetes, obesity and chronic kidney disease. The present review focuses on renal mechanisms involved in the development of this type of hypertension. 2. The renal medullary circulation plays an important role in the development of salt-sensitive hypertension. In vivo animal studies have demonstrated that the balance between nitric oxide (NO) and reactive oxygen species (ROS) in the renal medulla is an important element of salt-sensitive hypertension. The medullary thick ascending limb (mTAL) in the outer medulla is an important source of NO and ROS production and we have explored the mechanisms that stimulate their production, as well as the effects of NO superoxide and hydrogen peroxide on mTAL tubular sodium reabsorption and the regulation of medullary blood flow. 3. Angiotensin II-stimulated NO produced in the mTAL is able to diffuse from the renal mTAL to the surrounding vasa recta capillaries, providing a mechanism by which to increase medullary blood flow and counteract the direct vasoconstrictor effects of angiotensin II. Enhanced oxidative stress attenuates NO diffusion in this region. 4. Carbonyl stress, like oxidative stress, can also play an important role in the pathogenesis of chronic kidney disease, such as insulin resistance, salt-sensitive hypertension and renal vascular complications. 5. Despite the large number of studies undertaken in this area, there is as yet no drug available that directly targets renal ROS. Oxidative and/or carbonyl stress may be the next target of drug discovery to protect against salt-sensitive hypertension and associated end-organ damage. PMID:22150746

  13. Renal Tumor Biopsy Technique

    PubMed Central

    Zhang, Lei; Li, Xue-Song; Zhou, Li-Qun

    2016-01-01

    Objective: To review hot issues and future direction of renal tumor biopsy (RTB) technique. Data Sources: The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. Study Selection: We included all the relevant articles on RTB technique in English, with no limitation of study design. Results: Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended. Conclusion: In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors. PMID:27174334

  14. Tofacitinab in Renal Transplantation

    PubMed Central

    Zand, Martin S.

    2013-01-01

    Tofacitinib (tositinib, CP-690,550) is a small molecule inhibitor of Janus associated kinases, primarily JAK3 and JAK2, which inhibits cytokine signaling through the IL-2Rγ chain. In this article, we review the mechanism of action of tofacitinib, and pre-clinical and clinical data regarding its use in solid organ transplantation thus far. It is hoped that tofacitinib may form the basis for calcineurin-free immunosuppression, improving renal function while eliminating calcineurin inhibitor renal toxicity. Current studies suggest that tofacitinib is an effective immunosuppressive agent for renal transplantation, but it's use in current protocols carries an increased risk of CMV, BK, and EBV viral infection, anemia and leukopenia, and post-transplant lymphoproliferative disorder. PMID:23849222

  15. Contemporary Management of Renal Trauma

    PubMed Central

    Shoobridge, Jennifer J; Corcoran, Niall M; Martin, Katherine A; Koukounaras, Jim; Royce, Peter L; Bultitude, Matthew F

    2011-01-01

    In the management of renal trauma, surgical exploration inevitably leads to nephrectomy in all but a few specialized centers. With current management options, the majority of hemodynamically stable patients with renal injuries can be successfully managed nonoperatively. Improved radiographic techniques and the development of a validated renal injury scoring system have led to improved staging of injury severity that is relatively easy to monitor. This article reviews a multidisciplinary approach to facilitate the care of patients with renal injury. PMID:21941463

  16. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  17. Effects of an anti-G suit on the hemodynamic and renal responses to positive /+Gz/ acceleration

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

    The effects of the currently used U.S. Air Force (CSU-12/P) anti-G suit on renal function during positive radial acceleration (+Gz) were assessed in seven normal male subjects in balance on a 200 meq sodium diet. Following suit inflation in the seated position, +2.0 Gz for 30 min resulted in a decrease in the rate of sodium excretion from 125 plus or minus 19 to 60 plus or minus 14 microeq/min, which persisted during a 25-min recovery period. Fractional excretion of sodium also decreased significantly during +Gz. The magnitude of the antinatriuresis was indistinguishable from that observed during +Gz without suit inflation. In contrast to the antinatriuresis observed during centrifugation without suit, however, the antinatriuresis with suit was mediated primarily by an enhanced tubular reabsorption of sodium.

  18. Effects of D-glucose, 2-deoxy-D-glucose and D-xylose on renal function in the rat.

    PubMed Central

    Garland, H O; Singh, H J

    1988-01-01

    1. Standard renal clearance techniques were used to investigate the effects of 2.5, 5 and 10% D-glucose, 2.5% 2-deoxy-D-glucose and 2.5% D-xylose on kidney function in male rats. 2. There was no consistent effect of D-glucose on urinary sodium output except with 10% D-glucose, where sodium excretion was raised compared to controls. 3. An increased urinary calcium output was seen in all D-glucose-infused rats compared to controls. Values obtained for 2.5, 5 and 10% glucose were respectively 32, 61 and 58% above control data. Neither 2-deoxy-D-glucose nor D-xylose produced a calciuresis. 4. The increased urinary calcium excretion in D-glucose rats was the result of a reduction in fractional calcium reabsorption. Glomerular filtration rate (GFR) was unchanged. It was not dependent upon glycosuria or a diuresis. PMID:3418534

  19. Renal adaptation during hibernation

    PubMed Central

    Martin, Sandra L.; Jain, Swati; Keys, Daniel; Edelstein, Charles L.

    2013-01-01

    Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart, and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system, and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and reimplantation during transplantation. PMID:24049148

  20. Autophagy in renal diseases.

    PubMed

    De Rechter, Stéphanie; Decuypere, Jean-Paul; Ivanova, Ekaterina; van den Heuvel, Lambertus P; De Smedt, Humbert; Levtchenko, Elena; Mekahli, Djalila

    2016-05-01

    Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production. In the healthy kidney, autophagy plays an important role in the homeostasis and viability of renal cells such as podocytes and tubular epithelial cells and of immune cells. Recently, evidence is mounting that (dys)regulation of autophagy is implicated in the pathogenesis of various renal diseases, and might be an attractive target for new renoprotective therapies. In this review, we provide an overview of the role of autophagy in kidney physiology and kidney diseases. PMID:26141928

  1. Epidemiologic characteristics and risk factors for renal cell cancer

    PubMed Central

    Lipworth, Loren; Tarone, Robert E; Lund, Lars; McLaughlin, Joseph K

    2009-01-01

    Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches, including evaluation of gene–environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer. PMID:20865085

  2. Oxidant Mechanisms in Renal Injury and Disease

    PubMed Central

    Ratliff, Brian B.; Abdulmahdi, Wasan; Pawar, Rahul

    2016-01-01

    Abstract Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. Future Directions: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones. Antioxid. Redox Signal. 25, 119–146. PMID:26906267

  3. Physiology of the Renal Interstitium

    PubMed Central

    2015-01-01

    Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium. PMID:25813241

  4. Community Links

    ERIC Educational Resources Information Center

    Nelson, Mary

    1975-01-01

    At Moraine Valley Community College (Illinois), a chain of events, programs, activities, and services has linked the college and community in such areas as fine arts, ethnic groups, public services, community action, community service, and community education. (Author/NHM)

  5. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia.

    PubMed

    Zhang, Xiaoping; Imel, Erik A; Ruppe, Mary D; Weber, Thomas J; Klausner, Mark A; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey; Glorieux, Francis H; Portale, Anthony A; Insogna, Karl; Carpenter, Thomas O; Peacock, Munro

    2016-02-01

    In X-linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2 D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half-life was 16.4 days. The mean area under the concentration-time curve (AUCn ) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration-time curve (AUECn ) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2 D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn . Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration. PMID:26073451

  6. Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia.

    PubMed

    Zhang, Xiaoping; Peyret, Thomas; Gosselin, Nathalie H; Marier, J F; Imel, Erik A; Carpenter, Thomas O

    2016-04-01

    X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a novel human anti-FGF23 antibody for the treatment of XLH. The pharmacokinetics (PK) and pharmacodynamics (PD) models of KRN23 were assessed following subcutaneous dosing every 28 days over an initial 4-month dose escalation (0.05-0.6 mg/kg) and a subsequent 12-month titration period (0.1-1.0 mg/kg) in XLH adults. The PK of KRN23 was described by a 1-compartmental model with first-order absorption and elimination at doses ≥0.1 mg/kg. The elimination half-life was 17.8 days. Covariates did not affect KRN23 PK. Mean peak serum Pi was attained 7-10 days after dosing and progressively increased following each of the initial 4 doses with comparable peak values attained following the sixth through tenth doses with a slight decrease thereafter. A PK-PD model with a maximum effect (Emax ) and a time-varying effective concentration to reach 50% of Emax (EC50,t ) described data adequately. Typical Emax was 1.5 mg/dL. Typical EC50,t was 1780 ng/mL and 5999 ng/mL after first and last dose, respectively. PMID:26247790

  7. Link Analysis

    NASA Astrophysics Data System (ADS)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  8. Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations

    PubMed Central

    Blázquez-Medela, Ana M.; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M.; Romero, Miguel; Duarte, Juan M.; López-Hernández, Francisco J.; López-Novoa, José M.; Martínez-Salgado, Carlos

    2015-01-01

    Abstract Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys. We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage. Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments. The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening. KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

  9. Calcium Extrusion Pump PMCA4: A New Player in Renal Calcium Handling?

    PubMed Central

    van Loon, Ellen P. M.; Little, Robert; Prehar, Sukhpal; Bindels, René J. M.; Cartwright, Elizabeth J.; Hoenderop, Joost G. J.

    2016-01-01

    Calcium (Ca2+) is vital for multiple processes in the body, and maintenance of the electrolyte concentration is required for everyday physiological function. In the kidney, and more specifically, in the late distal convoluted tubule and connecting tubule, the fine-tuning of Ca2+ reabsorption from the pro-urine takes place. Here, Ca2+ enters the epithelial cell via the transient receptor potential vanilloid receptor type 5 (TRPV5) channel, diffuses to the basolateral side bound to calbindin-D28k and is extruded to the blood compartment via the Na+/Ca2+ exchanger 1 (NCX1) and the plasma membrane Ca2+ ATPase (PMCA). Traditionally, PMCA1 was considered to be the primary Ca2+ pump in this process. However, in recent studies TRPV5-expressing tubules were shown to highly express PMCA4. Therefore, PMCA4 may have a predominant role in renal Ca2+ handling. This study aimed to elucidate the role of PMCA4 in Ca2+ homeostasis by characterizing the Ca2+ balance, and renal and duodenal Ca2+-related gene expression in PMCA4 knockout mice. The daily water intake of PMCA4 knockout mice was significantly lower compared to wild type littermates. There was no significant difference in serum Ca2+ level or urinary Ca2+ excretion between groups. In addition, renal and duodenal mRNA expression levels of Ca2+-related genes, including TRPV5, TRPV6, calbindin-D28k, calbindin-D9k, NCX1 and PMCA1 were similar in wild type and knockout mice. Serum FGF23 levels were significantly increased in PMCA4 knockout mice. In conclusion, PMCA4 has no discernible role in normal renal Ca2+ handling as no urinary Ca2+ wasting was observed. Further investigation of the exact role of PMCA4 in the distal convoluted tubule and connecting tubule is required. PMID:27101128

  10. Kidney Injury Molecule-1 Enhances Endocytosis of Albumin in Renal Proximal Tubular Cells.

    PubMed

    Zhao, Xueying; Jiang, Chen; Olufade, Rebecca; Liu, Dong; Emmett, Nerimiah

    2016-04-01

    Receptor-mediated endocytosis plays an important role in albumin reabsorption by renal proximal tubule epithelial cells. Kidney injury molecule-1 (KIM-1) is a scavenger receptor that is upregulated on the apical membrane of proximal tubules in proteinuric kidney disease. In this study, we examined the cellular localization and functional role of KIM-1 in cultured renal tubule epithelial cells (TECs). Confocal immunofluorescence microscopy reveals intracellular and cell surface localization of KIM-1 in primary renal TECs. Albumin stimulation resulted in a redistribution of KIM-1 and tight junction protein zonula occludens-1 in primary TEC monolayer. An increase in albumin internalization was observed in both primary TECs expressing endogenous KIM-1 and rat kidney cell line (NRK-52E) overexpressing exogenous KIM-1. KIM-1-induced albumin accumulation was abolished by its specific antibody. Moreover, endocytosed KIM-1 and its cargo proteins were delivered from endosomes to lysosomes for degradation in a clathrin-dependent pathway. Supportive evidence includes (1) detection of KIM-1 in Rab5-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes, (2) colocalization of KIM-1 and clathrin in the intracellular vesicles, and (3) blockade of KIM-1-mediated albumin internalization by chlorpromazine, an inhibitor of clathrin-dependent endocytosis. KIM-1 expression was upregulated by albumin but downregulated by transforming growth factor-β1. Taken together, our data indicate that KIM-1 increases albumin endocytosis in renal tubule epithelial cells, at least partially via a clathrin-dependent mechanism. J. Cell. Physiol. 231: 896-907, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332568

  11. Effect of chronic poisoning with aluminum on the renal handling of phosphate in the rat.

    PubMed

    Mahieu, S; Calvo, M L

    1998-01-16

    The effects of aluminum on renal function and phosphate handling were studied using clearance techniques in chronically-intoxicated rats. Rats were given aluminum hydroxide (80 mg/kg b.w., i.p.), three times per week during 6 months. The phosphate tubular transport capacity was evaluated by determining the maximum tubular transport (TmRPi) and the fractional excretion of phosphate (FE% Pi) during the infusion of phosphate solutions with increasing concentrations (0, 9, 18, 33 mM). Parathyroid gland function was studied using indirect methods: calcemia recovery after EDTA administration and the nephrogenic excretion of cAMP as indicative of renal PTH actions, by RIA. The systemic acid base status was determined and food intake and rat growth were controlled in both groups. No changes were observed in the renal function. Pi reabsorption values per ml glomerular filtration rate (TRPi/GFR microg/ml) for different Pi plasmatic concentrations were distributed following a saturation curve compatible with a saturation kinetics. Aluminum increased TmRPi/GFR in treated animals (T) 76+/-4 as compared with control animals (C) 57+/-7 microg/ml, without a statistical modification in the apparent affinity. The FE% Pi and FE% Na were significantly lower in treated animals than in control animals. There were neither systemic variations in the acid-base balance nor in the Ca and Pi concentrations in plasma. The calcemia recovery following a hypocalcemic stimulus and the nephrogenic excretion of cAMP (T: 44+/-4; C: 91+/-7 pmol/min) were diminished. Considering all these facts, it can be postulated that the aluminum renal effect is associated from a decrease in PTH phosphaturic capacity. Nevertheless, other associated factors like minor phosphate intestinal absorption rate may not be disregarded, even though there were no significant intake variations. PMID:9544698

  12. Significant impact of transient deterioration of renal function on dosimetry in PRRT.

    PubMed

    Van Binnebeek, Sofie; Baete, Kristof; Terwinghe, Christelle; Vanbilloen, Bert; Haustermans, Karin; Mortelmans, Luc; Borbath, Ivan; Van Cutsem, Eric; Verslype, Chris; Mottaghy, Felix M; Verbruggen, Alfons; Deroose, Christophe M

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration. PMID:22961123

  13. Combination Therapy with Losartan and α-Tocopherol in Acute Ureteral Obstruction-Induced Renal Excretory Dysfunction and Acidification Defect

    PubMed Central

    Gheitasi, Izadpanah; Moosavi, Seyed Mostafa

    2014-01-01

    Background: Previous study by the authors showed that a-tocopherol prevents oxidative stress but would not improve depressed excretory variables in post-obstructed kidney (POK) after release of 24-h unilateral ureteral obstruction (UUO). This study is a supplementary investigation on the effects of a-tocopherol combined with an antagonist of angiotensin-II type-1 (AT1) receptor on renal dysfunction following release of acute UUO. Methods: The left ureter was ligated in different groups of male Sprague-Dawley rats that received normal saline, losartan or losartan/a-tocopherol (n=6 in each group). After releasing 24-h UUO, urine of each kidney was separately collected under paraffin during 1-3 h of post-release period and then both kidneys were removed for measuring malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP). Results: Losartan-treatment decreased MDA and increased FRAP, creatinine-clearance and sodium-reabsorption in POK, while co-treatment with losartan and a-tocopherol not only augmented improvement in these variables but also elevated potassium-excretion, free-water reabsorption and urine-osmolality. However, UUO-induced fall in urinary pCO2 and rise in pH and bicarbonate-excretion of POK were ameliorated equally with losartan and losartan/a-tocopherol. Conclusion: Activation of AT1-receptor contributes to the development of renal distal acidification defect induced by acute ureteral obstruction. The co-treatment with losartan and a-tocopherol showed that their effects on preventing oxidative stress along with ameliorating glomerular filtration and tubular fluid-delivery in POK could lead to improvement in tubular transport of sodium and potassium as well as urine-concentrating ability at the early post-release period. PMID:25031488

  14. Uroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway

    PubMed Central

    da Silva Lima, Vanessa; Crajoinas, Renato O.; Carraro-Lacroix, Luciene R.; Godinho, Alana N.; Dias, João L. G.; Dariolli, Rafael; Girardi, Adriana C. C.; Fonteles, Manassés C.; Malnic, Gerhard

    2014-01-01

    Cumulative evidence suggests that guanylin peptides play an important role on electrolyte homeostasis. We have previously reported that uroguanylin (UGN) inhibits bicarbonate reabsorption in a renal distal tubule. In the present study, we tested the hypothesis that the bicarbonaturic effect of UGN is at least in part attributable to inhibition of H+-ATPase-mediated hydrogen secretion in the distal nephron. By in vivo stationary microperfusion experiments, we were able to show that UGN inhibits H+-ATPase activity by a PKG-dependent pathway because KT5823 (PKG inhibitor) abolished the UGN effect on distal bicarbonate reabsorption and H89 (PKA inhibitor) was unable to prevent it. The in vivo results were confirmed by the in vitro experiments, where we used fluorescence microscopy to measure intracellular pH (pHi) recovery after an acid pulse with NH4Cl. By this technique, we observed that UGN and 8 bromoguanosine-cGMP (8Br-cGMP) inhibited H+-ATPase-dependent pHi recovery and that the UGN inhibitory effect was abolished in the presence of the PKG inhibitor. In addition, by using RT-PCR technique, we verified that Madin-Darby canine kidney (MDCK)-C11 cells express guanylate cyclase-C. Besides, UGN stimulated an increase of both cGMP content and PKG activity but was unable to increase the production of cellular cAMP content and PKA activity. Furthermore, we found that UGN reduced cell surface abundance of H+-ATPase B1 subunit in MDCK-C11 and that this effect was abolished by the PKG inhibitor. Taken together, our data suggest that UGN inhibits H+-ATPase activity and surface expression in renal distal cells by a cGMP/PKG-dependent pathway. PMID:25031022

  15. Malignancy after renal transplantation.

    PubMed

    Zeier, Martin; Hartschuh, Wolfgang; Wiesel, Manfred; Lehnert, Thomas; Ritz, Eberhard

    2002-01-01

    Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression. PMID:11774131

  16. Metabolomics and Renal Disease

    PubMed Central

    Rhee, Eugene P.

    2015-01-01

    Purpose of review This review summarizes recent metabolomics studies of renal disease, outlining some of the limitations of the literature to date. Recent findings The application of metabolomics in nephrology research has expanded from initial analyses of uremia to include both cross-sectional and longitudinal studies of earlier stages of kidney disease. Although these studies have nominated several potential markers of incident CKD and CKD progression, lack of overlap in metabolite coverage has limited the ability to synthesize results across groups. Further, direct examination of renal metabolite handling has underscored the substantial impact kidney function has on these potential markers (and many other circulating metabolites). In experimental studies, metabolomics has been used to identify a signature of decreased mitochondrial function in diabetic nephropathy and a preference for aerobic glucose metabolism in PKD; in each case, these studies have outlined novel therapeutic opportunities. Finally, as a complement to the longstanding interest in renal metabolite clearance, the microbiome has been increasingly recognized as the source of many plasma metabolites, including some with potential functional relevance to CKD and its complications. Summary The high-throughput, high-resolution phenotyping enabled by metabolomics technologies has begun to provide insight on renal disease in clinical, physiologic, and experimental contexts. PMID:26050125

  17. Ablative therapies for renal tumors

    PubMed Central

    Ramanathan, Rajan; Leveillee, Raymond J.

    2010-01-01

    Owing to an increased use of diagnostic imaging for evaluating patients with other abdominal conditions, incidentally discovered kidney masses now account for a majority of renal tumors. Renal ablative therapy is assuming a more important role in patients with borderline renal impairment. Renal ablation uses heat or cold to bring about cell death. Radiofrequency ablation and cryoablation are two such procedures, and 5-year results are now emerging from both modalities. Renal biopsy at the time of ablation is extremely important in order to establish tissue diagnosis. Real-time temperature monitoring at the time of radiofrequency ablation is very useful to ensure adequacy of ablation. PMID:21789083

  18. Impact of renal medullary three-dimensional architecture on oxygen transport.

    PubMed

    Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

    2014-08-01

    We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the

  19. Direct effect of vanadium on citrate uptake by rat renal brush border membrane vesicles (BBMV).

    PubMed

    Sato, Kazuhiro; Kusaka, Yukinori; Akino, Hironobu; Kanamaru, Hiroshi; Okada, Kenichiro

    2002-07-01

    Vanadium pentoxide is used as a catalyst and a ferrovanadium alloy ingredient in automotive steels and in jet engines and airframes. In addition, vanadium is found in fuel oils. Thus, occupational exposures to vanadium pentoxide and trioxide may occur during the cleaning of oil-fired ship boilers, and from oil-fired power station boilers. Occupational exposure to vanadium pentoxide induces green tongue, asthmatic symptoms and albuminuria with cast. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In this study, we exposed rat renal brush border membrane vesicles (BBMV) to vanadium pentoxide and examined their citrate uptake characteristics. The preincubation of BBMV with 1 mM V2O5 for 8 hours significantly inhibited citrate uptake compared with that of BBMV without V2O5, preincubation. These findings indicate that the preincubation of BBMV with vanadium pentoxide results in a time-dependent inhibition of citrate uptake by BBMV. These findings might contribute to nephrotoxicity in vanadium exposure. PMID:12141377

  20. How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure.

    PubMed

    Digne-Malcolm, Holly; Frise, Matthew C; Dorrington, Keith L

    2016-01-01

    Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca(++)-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents. PMID:27524972

  1. Thyroid hormones increase Na -H exchange activity in renal brush border membranes

    SciTech Connect

    Kinsella, J.; Sacktor, B.

    1985-06-01

    Na -H exchange activity, i.e., amiloride-sensitive Na and H flux, in renal proximal tubule brush border (luminal) membrane vesicles was increased in the hyperthyroid rat and decreased in the hypothyroid rat, relative to the euthyroid animal. A positive correlation was found between Na -H exchange activity and serum concentrations of thyroxine (T4) and triiodothyronine (T3). The thyroid status of the animal did not alter amiloride-insensitive Na uptake. The rate of passive pH gradient dissipation was higher in membrane vesicles from hyperthyroid rats compared to the rate in vesicles from hypothyroid animals, a result which would tend to limit the increase in Na uptake in vesicles from hyperthyroid animals. Na -dependent phosphate uptake was increased in membrane vesicles from hyperthyroid rats; Na -dependent D-glucose and L-proline uptakes were not changed by the thyroid status of the animal. The effect of thyroid hormones in increasing the uptake of Na in the brush border membrane vesicle is consistent with the action of the hormones in enhancing renal Na reabsorption.

  2. How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure

    PubMed Central

    Digne-Malcolm, Holly; Frise, Matthew C.; Dorrington, Keith L.

    2016-01-01

    Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents. PMID:27524972

  3. Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.

    PubMed

    Horita, Shoko; Nakamura, Motonobu; Satoh, Nobuhiko; Suzuki, Masashi; Seki, George

    2015-01-01

    Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema. PMID:26074951

  4. Nephrology and astrology--is there a link?

    PubMed

    Hughes, S

    1990-07-01

    Astrologers presume a link between the susceptibility of particular organs to disease and signs of the Zodiac. A simple test of the positive connection between renal disease and the sign of Libra was undertaken by studying the birth dates of consecutive nephrology in-patient admissions. No significant link was found on analysis, thus disproving the traditional astrologers' claims. PMID:2206825

  5. Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity

    PubMed Central

    Strand, Joanna; Nordeman, Patrik; Honarvar, Hadis; Altai, Mohamed; Orlova, Anna; Larhed, Mats; Tolmachev, Vladimir

    2015-01-01

    Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of 125I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using 125I-IPEM with an overall yield of 45±3 %. 125I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of 125I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g−1at 1 and 4 h after injection, respectively) was significantly lower than uptake of 125I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g−1at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity. PMID:25969816

  6. Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1

    PubMed Central

    Nagamori, Shushi; Wiriyasermkul, Pattama; Guarch, Meritxell Espino; Okuyama, Hirohisa; Nakagomi, Saya; Tadagaki, Kenjiro; Nishinaka, Yumiko; Bodoy, Susanna; Takafuji, Kazuaki; Okuda, Suguru; Kurokawa, Junko; Ohgaki, Ryuichi; Nunes, Virginia; Palacín, Manuel; Kanai, Yoshikatsu

    2016-01-01

    Heterodimeric amino acid transporters play crucial roles in epithelial transport, as well as in cellular nutrition. Among them, the heterodimer of a membrane protein b0,+AT/SLC7A9 and its auxiliary subunit rBAT/SLC3A1 is responsible for cystine reabsorption in renal proximal tubules. The mutations in either subunit cause cystinuria, an inherited amino aciduria with impaired renal reabsorption of cystine and dibasic amino acids. However, an unsolved paradox is that rBAT is highly expressed in the S3 segment, the late proximal tubules, whereas b0,+AT expression is highest in the S1 segment, the early proximal tubules, so that the presence of an unknown partner of rBAT in the S3 segment has been proposed. In this study, by means of coimmunoprecipitation followed by mass spectrometry, we have found that a membrane protein AGT1/SLC7A13 is the second partner of rBAT. AGT1 is localized in the apical membrane of the S3 segment, where it forms a heterodimer with rBAT. Depletion of rBAT in mice eliminates the expression of AGT1 in the renal apical membrane. We have reconstituted the purified AGT1-rBAT heterodimer into proteoliposomes and showed that AGT1 transports cystine, aspartate, and glutamate. In the apical membrane of the S3 segment, AGT1 is suggested to locate itself in close proximity to sodium-dependent acidic amino acid transporter EAAC1 for efficient functional coupling. EAAC1 is proposed to take up aspartate and glutamate released into luminal fluid by AGT1 due to its countertransport so that preventing the urinary loss of aspartate and glutamate. Taken all together, AGT1 is the long-postulated second cystine transporter in the S3 segment of proximal tubules and a possible candidate to be involved in isolated cystinuria. PMID:26739563

  7. RENAL INSUFFICIENCY FOLLOWING TRYPSIN INJECTION INTO THE RENAL ARTERIES.

    PubMed

    Friedman, M; Katz, L N

    1938-09-30

    1. The injection of trypsin into both renal arteries of the dog was found to cause an acute necrosis of large sections of the kidney, an immediate excretory insufficiency, and a transient hypertension. 2. Dogs surviving the acute phase of the trypsin injection, developed a chronic renal excretory insufficiency with no hypertension, despite the severity and duration of the renal excretory insufficiency. 3. The application of a Goldblatt clamp to the renal artery of one of the two kidneys, previously injected with trypsin, led to a rise in blood pressure which returned at once to normal when the ischemic kidney was removed, even though the pre-existing renal excretory insufficiency was augmented. This experience demonstrated unequivocally that chronic renal excretory insufficiency and hypertension are not directly related. 4. The application of a Goldblatt clamp to the renal artery of one kidney and the simultaneous injection of trypsin into the other led to a hypertension. The later removal of the ischemic kidney led to a severe renal excretory insufficiency, at the same time the pre-existing hypertension disappeared. This indicated again that renal excretory insufficiency and renal ischemia produced different phenomena and that the former had no direct relation to hypertension. PMID:19870800

  8. The cardiovascular and renal functional responses to the 5-HT1A receptor agonist flesinoxan in two rat models of hypertension.

    PubMed Central

    Chamienia, A. L.; Johns, E. J.

    1996-01-01

    1. This study investigated the importance of renal sympathetic nerves in regulating sodium and water excretion from the kidneys of stroke prone spontaneously hypertensive and 2K1C Goldblatt hypertensive rats anaesthetized with chloralose/urethane (17.5/300 mg initially and supplemented at regular intervals), and prepared for measurement of renal function. 2. In stroke prone spontaneously hypertensive rats, flesinoxan, 30-1000 micrograms kg-1, i.v., caused graded reductions in blood pressure and heart rate of 74 +/- 5 mmHg and 63 +/- 9 beats min-1, respectively at the highest dose (P < 0.001). Renal blood flow did not change at any dose of drug while glomerular filtration rate fell by some 20% (P < 0.001) at the highest dose of drug, absolute and fractional sodium excretions, approximately doubled at 100 micrograms kg-1, and thereafter fell to below the baseline level at 1000 micrograms kg-1. 3. This pattern of excretory response was abolished following acute renal denervation when flesinoxan caused dose-related reductions in urine flow and sodium excretion, similar to that obtained by a mechanical reduction of renal perfusion pressure. 4. Flesinoxan administration (30-1000 micrograms kg-1, i.v.) into 2K1C Goldblatt hypertensive rats caused a maximum decrease in blood pressure and heart rate (both P < 0.001) of 34 +/- 3 mmHg and 20 +/- 6 beats min-1 and while renal blood flow and glomerular filtration rate were autoregulated, from 160 to 125 mmHg, there were dose-related decreases in urine volume and sodium excretion from the clipped and non-clipped kidneys of approximately 50-60% at the highest dose. 5. These findings suggest that in the stroke prone spontaneously hypertensive rat the renal nerves importantly control sodium and water reabsorption at the level of the tubules, whereas in 2K1C Goldblatt hypertensive rats, they play a minor role. PMID:8864520

  9. Linked Systems.

    ERIC Educational Resources Information Center

    Association of Research Libraries, Washington, DC.

    Three papers are compiled here for research library directors: (1) "Background: Open Systems Interconnection," in which David F. Bishop provides fundamental background information to explain the concept of the emerging technology of linked systems and open systems interconnection--i.e., an agreed upon standard set of conventions or rules that,…

  10. Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension.

    PubMed

    Bełtowski, Jerzy; Jamroz-Wiśniewska, Anna; Borkowska, Ewelina; Wójcicka, Grazyna

    2004-01-01

    Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin has not been elucidated. We investigated the effect of experimental hyperleptinemia on renal function, renal Na(+), K(+)-ATPase and ouabain-sensitive H(+), K(+)-ATPase activities in the rat. Leptin administered for 7 days (0.25 mg/kg twice daily sc) decreased food intake on 6th and 7th day of treatment but had no effect on body weight. Systolic blood pressure was 30.5% higher in leptin-treated animals. Urinary excretion of sodium decreased by 35.0% following leptin treatment. Leptin had no effect on potassium and phosphate excretion as well as on creatinine clearance. The activity of Na(+), K(+)-ATPase in the renal cortex and medulla was higher in leptin-treated rats by 32.4% and 84.2%, respectively. In contrast, leptin had no effect on either cortical or medullary ouabain-sensitive H(+), K(+)-ATPase. In pair-fed group, in which food intake was reduced to the level observed in leptin-treated group, no changes in sodium metabolism and renal Na(+), K(+)-ATPase were observed. Leptin decreased urinary excretion of nitric oxide metabolites by 55.0% and urinary excretion of cGMP by 26.3%. Plasma concentration of atrial natriuretic peptide tended to be higher and urinary excretion of urodilatin was 64.9% higher in leptin-treated animals. These data suggest that hyperleptinemia decreases natriuresis by up-regulating Na(+), K(+)-ATPase and stimulating tubular sodium reabsorption. This effect is mediated, at least in part, by deficiency of nitric oxide (NO). Abnormal renal sodium retention and vasoconstriction associated with NO deficiency may contribute to leptin-induced hypertension and to blood pressure elevation in hypertensive obese individuals. PMID:15156072

  11. Renal osteodystrophy, phosphate homeostasis, and vascular calcification.

    PubMed

    Hruska, Keith A; Saab, Georges; Mathew, Suresh; Lund, Richard

    2007-01-01

    New advances in the pathogenesis of renal osteodystrophy (ROD) change the perspective from which many of its features and treatment are viewed. Calcium, phosphate, parathyroid hormone (PTH), and vitamin D have been shown to be important determinants of survival associated with kidney diseases. Now ROD dependent and independent of these factors is linked to survival more than just skeletal frailty. This review focuses on recent discoveries that renal injury impairs skeletal anabolism decreasing the osteoblast compartment of the skeleton and consequent bone formation. This discovery and the discovery that PTH regulates the hematopoietic stem cell niche alters our view of secondary hyperparathyroidism in chronic kidney disease (CKD) from that of a disease to that of a necessary adaptation to renal injury that goes awry. Furthermore, ROD is shown to be an underappreciated factor in the level of the serum phosphorus in CKD. The discovery and the elucidation of the mechanism of hyperphosphatemia as a cardiovascular risk in CKD change the view of ROD. It is now recognized as more than a skeletal disorder, it is an important component of the mortality of CKD that can be treated. PMID:17635820

  12. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time.

    PubMed

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  13. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time

    PubMed Central

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  14. Dental management of people with renal disease and renal transplants.

    PubMed

    Ferguson, C A; Whyman, R A

    1998-09-01

    Chronic renal failure is the result of progressive loss of functioning nephrons leading to loss of renal function and accumulation of excretory products. Loss of the regulatory and excretory functions of the kidneys causes oral manifestations and multiple complications which have implications for dental care. Dental management of patients with renal failure and renal transplants involves consideration of specific haematological and cardiovascular effects, and implications for the prescribing and use of pharmaceuticals. It also requires the dentist to appreciate the potential for involvement of multiple organ systems in the disease process and the implications this has for dental care. The orofacial manifestations of chronic renal failure are secondary to systemic manifestations and are not specific to the diagnosis of end-stage renal disease. PMID:9775650

  15. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    PubMed

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  16. Bilateral renal calculi

    PubMed Central

    Sreenevasan, G

    1974-01-01

    Bilateral renal calculi were present in 114 (10.7%) of 1,070 cases of proved urinary calculus admitted to the Urological Department of the General Hospital, Kuala Lumpur, during the period November 1968—May 1973. The management of bilateral renal calculi is discussed with reference to the first 100 cases in this series. The introduction of renography has greatly facilitated the decision as to which kidney should be operated on first. The management of patients with and without uraemia is discussed and the use of the modified V and V—Y incisions for the removal of staghorn calculi is described. Complications and results are briefly reviewed. ImagesFig. 1Fig. 4Fig. 6Fig. 7 PMID:4845653

  17. Inherited renal carcinomas.

    PubMed

    Kawashima, Akira; Young, Scott W; Takahashi, Naoki; King, Bernard F; Atwell, Thomas D

    2016-06-01

    Hereditary forms of kidney carcinoma account for 5-8% of all malignant kidney neoplasms. The renal tumors are often multiple and bilateral and occur at an earlier age. Each of the hereditary kidney carcinoma syndromes is associated with specific gene mutations as well as a specific histologic type of kidney carcinoma. The presence of associated extrarenal manifestations may suggest a hereditary kidney cancer syndrome. Radiology is most commonly used to screen and manage patients with hereditary kidney cancer syndromes. This manuscript reviews the clinical and imaging findings of well-defined inherited kidney cancer syndromes including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal carcinoma syndrome, hereditary leiomyomatosis and RCC syndrome, tuberous sclerosis complex, and Lynch syndrome. PMID:27108134

  18. Renal Clearance of Nanoparticles

    PubMed Central

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2008-01-01

    SUMMARY The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter (HD) by over 15 nm and prevented renal excretion. A final HD smaller than 5.5 nm resulted in rapid and efficient urinary excretion, and elimination of QDs from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. PMID:17891134

  19. Renal injury in sport.

    PubMed

    Holmes, F Clarke; Hunt, Jeremy J; Sevier, Thomas L

    2003-04-01

    Hematuria is the most common presenting sign of renal injury. Its presence in athletes may indicate a benign entity such as exercise-induced hematuria or a more serious injury in the presence of trauma. Exercise-induced hematuria can originate in the kidney, bladder, urethra, or prostate. The type of activity, as well as activity duration and intensity, contributes to its development. A wide differential diagnosis must be considered if hematuria persists longer than 24 to 72 hours. Trauma to the kidney can occur from a direct blow or deceleration; contact and collision sports are most commonly involved. Fortunately, most sports-related renal trauma is mild, and can be managed expectantly. A sporting injury rarely results in nephrectomy. Determining return to play for the athlete with a single kidney remains a controversial issue that requires patient education and an individualized approach. PMID:12831667

  20. Renal stones in pregnancy

    PubMed Central

    Gibbons, Norma; DasGupta, Ranan

    2014-01-01

    Diagnosis and treatment of renal stones during pregnancy is a complex problem. Risks to the fetus from ionising radiation and interventional procedures need to be balanced with optimising clinical care for the mother. Management of such patients requires a clear understanding of available options, with a multidisciplinary team approach. In this review, we discuss the role of different diagnostic tests including ultrasound, magnetic resonance urography, and computerized tomography. We also provide an update on recent developments in the treatment of renal stones during pregnancy. Expectant management remains first-line treatment. Where definitive treatment of the stone is required, new evidence suggests that ureteroscopic stone removal may be equally safe, and possibly better than traditional temporising procedures.

  1. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  2. Renal Infarction Caused by Isolated Spontaneous Renal Artery Intramural Hematoma

    PubMed Central

    Park, Sihyung; Lee, Ga Hee; Jin, Kyubok; Park, Kang Min; Kim, Yang Wook; Park, Bong Soo

    2015-01-01

    Patient: Male, 46 Final Diagnosis: Renal infarction Symptoms: Flank pain Medication: — Clinical Procedure: CT Specialty: Nephrology Objective: Rare disease Background: Acute renal infarction is an uncommon condition resulting from an obstruction or a decrease in renal arterial blood flow. Isolated spontaneous renal artery intramural hematoma is a rare cause of renal infarction. Case Report: A 46-year-old healthy man presented to our emergency room because of sudden onset of severe right flank pain. An enhanced abdominal computed tomography scan showed a low-attenuated lesion in the lateral portion of the right kidney but no visible thromboembolisms in the main vessels. Computed tomography angiography revealed acute infarction resulting from intramural hematoma of the anterior segmental artery of the right kidney, with distal occlusion. Conclusions: The rarity and non-specific clinical presentation of renal infarction often lead to a delayed diagnosis that may result in impaired renal function. Clinical suspicion is important in the early diagnosis, and intramural hematoma of the renal artery should be considered the cause of renal infarction even in healthy patients without pre-disposing factors. PMID:26596500

  3. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  4. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  5. Percutaneous renal cryoablation: current status.

    PubMed

    Mazaris, Evangelos M; Varkarakis, Ioannis M; Solomon, Stephen B

    2008-04-01

    Over the last 13 years, renal cryoablation has emerged as a promising technique for the treatment of solid renal tumors. The improvement in imaging modalities such as ultrasound, computed tomography and MRI, as well as the introduction of thinner probes, has led to the spread of the minimally invasive percutaneous approach. We review the historical background of percutaneous renal cryoablation (PRC), present its basic principles, mention the contemporary clinical data and outcomes of this technique and suggest future directions for its wider application in renal tumors. Early results have demonstrated that it may offer an alternative for the treatment of small renal masses with the advantages of minimal complications, spared renal function, decreased overall costs and equivalent oncologic efficacy. Long-term results are required in order to apply this minimally invasive technique to a broader spectrum of patients. PMID:18407738

  6. Drug-induced renal disorders.

    PubMed

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  7. H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

    NASA Astrophysics Data System (ADS)

    Wall, Susan M.; Klein, Janet D.

    2008-09-01

    The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

  8. Increased Renal Solute Excretion in Rats Following Space Flight

    NASA Technical Reports Server (NTRS)

    Wade, Charles E.; Moore, A. L.; Morey-Holton, E.

    1995-01-01

    Following space flight a diuresis, due to an increase in free water clearance, has been suggested in humans. To assess the effects of space flight on renal function, rats were flown in space for 14 days. Rats were divided into three groups; vivarium controls (V;n=6; housed 2/shoe box cage), flight controls (FC;n=6; group housed in a flight cage), and flight animals (F;n=6). Upon landing all animals were placed into individual metabolic cages. Urine was collected daily for 7 days and every other day for 14 days. Urine output was increased (p less than 0.05; ANOVA) following flight for 3 days. On postflight day 1, flow rates were, V=6.8 plus or minus 0.9, FC=8.711.8 and F=16.6 plus or minus 2.7 microliter/min. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate (V=7.9 plus or minus 0.9, FC=6.1 plus or minus 0.7 and F=13.5 plus or minus 0.7 uOsm/min). Creatinine excretion rate was increased over the first two postflight days. In the absence of changes in plasma creatinine, Na+, or K+ (samples obtained immediately post flight from similar rats compared to Day 14), GFR was increased following space flight. The increased excretion of solute was thus the result of increased delivery and decreased reabsorption. Osmotic clearance was increased (V=28, FC=27 and F=51 microliter/min), while free water clearance was decreased post flight (V=-21,FC=-18 and F=-34 microliter/min). In rats, the postflight diuresis is the result of an increase in solute (osmotic) excretion with an accompanying reduction in free water clearance.

  9. Multiple oncocytomas and renal carcinoma

    SciTech Connect

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma.

  10. Interleukin-17A Regulates Renal Sodium Transporters and Renal Injury in Angiotensin II-Induced Hypertension.

    PubMed

    Norlander, Allison E; Saleh, Mohamed A; Kamat, Nikhil V; Ko, Benjamin; Gnecco, Juan; Zhu, Linjue; Dale, Bethany L; Iwakura, Yoichiro; Hoover, Robert S; McDonough, Alicia A; Madhur, Meena S

    2016-07-01

    Angiotensin II-induced hypertension is associated with an increase in T-cell production of interleukin-17A (IL-17A). Recently, we reported that IL-17A(-/-) mice exhibit blunted hypertension, preserved natriuresis in response to a saline challenge, and decreased renal sodium hydrogen exchanger 3 expression after 2 weeks of angiotensin II infusion compared with wild-type mice. In the current study, we performed renal transporter profiling in mice deficient in IL-17A or the related isoform, IL-17F, after 4 weeks of Ang II infusion, the time when the blood pressure reduction in IL-17A(-/-) mice is most prominent. Deficiency of IL-17A abolished the activation of distal tubule transporters, specifically the sodium-chloride cotransporter and the epithelial sodium channel and protected mice from glomerular and tubular injury. In human proximal tubule (HK-2) cells, IL-17A increased sodium hydrogen exchanger 3 expression through a serum and glucocorticoid-regulated kinase 1-dependent pathway. In mouse distal convoluted tubule cells, IL-17A increased sodium-chloride cotransporter activity in a serum and glucocorticoid-regulated kinase 1/Nedd4-2-dependent pathway. In both cell types, acute treatment with IL-17A induced phosphorylation of serum and glucocorticoid-regulated kinase 1 at serine 78, and treatment with a serum and glucocorticoid-regulated kinase 1 inhibitor blocked the effects of IL-17A on sodium hydrogen exchanger 3 and sodium-chloride cotransporter. Interestingly, both HK-2 and mouse distal convoluted tubule 15 cells produce endogenous IL-17A. IL17F had little or no effect on blood pressure or renal sodium transporter abundance. These studies provide a mechanistic link by which IL-17A modulates renal sodium transport and suggest that IL-17A inhibition may improve renal function in hypertension and other autoimmune disorders. PMID:27141060

  11. A brief survey of aquaporins and their implications for renal physiology.

    PubMed

    Gade, Wayne; Robinson, Brooke

    2006-01-01

    Aquaporins (AQPs) are an important family of proteins that efficiently channel water through the cell membranes. Although water can diffuse across biological membranes at measurable rates, physiologists had long predicted the existence of channels to facilitate rapid reabsorption of water by renal tubular cells. With AQPs present, water can "gush" through the membrane at the extraordinary rate of three billion water molecules per second per aquaporin channel. In their absence, water only trickles across the hydrophobic lipid bilayers of cell membranes. Aquaporins have fascinated researchers over the last decade, culminating in the 2003 Nobel Prize for Chemistry given to their discoverer, Dr. Peter Agre. During the 1990s, scientists identified and characterized members of the mammalian aquaporin family, now designated as AQP0 through AQP10. AQPs are also found in many plant and bacterial species. However, their relevance to the clinical laboratory is only recently emerging. Dr. Agre's Nobel symposium address provides an excellent mini-review of aquaporins in medicine. Our understanding of renal physiology and pathophysiology has advanced greatly as we account for the subtle implications of various AQP systems. For example, nephrogenic diabetes insipidus (NDI), the inability to produce concentrated urine, can result from several different malfunctions in the AQP2 system controlled by anti-diuretic hormone (ADH). Virtually all mammalian cells incorporate aquaporins into their cell membranes, and many cells produce multiple aquaporins, each with a specific function. It is therefore not surprising that malfunctions have important clinical conditions. The present article discusses the implications of aquaporins for renal physiology, while the accompanying article is focused on the clinical aspects of aquaporins. PMID:16749243

  12. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice

    PubMed Central

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-01-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased. PMID:24396058

  13. Aquatic models for the study of renal transport function and pollutant toxicity.

    PubMed Central

    Miller, D S

    1987-01-01

    Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule. Images FIGURE 3. FIGURE 6. PMID:3297665

  14. Aquatic models for the study of renal transport function and pollutant toxicity.

    PubMed

    Miller, D S

    1987-04-01

    Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule. PMID:3297665

  15. Aquatic models for the study of renal transport function and pollutant toxicity

    SciTech Connect

    Miller, D.S.

    1987-04-01

    Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed (1) by other anionic xenobiotics that compete for secretory transport sites and (2) by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity and tissue heterogeneity that limit transport studies in proximal tubule.

  16. Controversies in the pathogenesis of HIV-associated renal diseases

    PubMed Central

    Bruggeman, Leslie A.; Nelson, Peter J.

    2009-01-01

    The two most common HIV-associated renal diseases, HIV-associated nephropathy and HIV-immune-complex kidney disease, share the common pathologic finding of hyperplasia within the glomerulus. Podocyte injury is central to the pathogenesis of these diseases; however, the source of the proliferating glomerular epithelial cell remains a topic of debate. Parenchymal injury has been linked to direct infection of renal epithelial cells by HIV-1, although the mechanism of viral entry into this non-lymphoid compartment is unclear. Although transgenic rodent models have provided insight into viral proteins responsible for inducing renal disease, such models have important limitations. Rodent HIV-1 models, for instance, cannot replicate all aspects of immune activation, a process that could have an important role in the pathogenesis PMID:19776779

  17. The renal scan in pregnant renal transplant patients

    SciTech Connect

    Goldstein, H.A.; Ziessman, H.A.; Fahey, F.H.; Collea, J.V.; Alijani, M.R.; Helfrich, G.B.

    1985-05-01

    With the greater frequency of renal transplant surgery, more female pts are becoming pregnant and carrying to term. In the renal allograft blood vessels and ureter may be compressed resulting in impaired renal function and/or, hypertension. Toxemia of pregnancy is seen more frequently than normal. Radionuclide renal scan monitoring may be of significant value in this high risk obstetrical pt. After being maintained during the pregnancy, renal function may also deteriorate in the post partum period. 5 pregnant renal transplant pts who delivered live babies had renal studies with Tc-99m DTPA to assess allograft perfusion and function. No transplanted kidney was lost during or after pregnancy as a result of pregnancy. No congenital anomalies were associated with transplant management. 7 studies were performed on these 5 pts. The 7 scans all showed the uterus/placenta. The bladder was always distorted. The transplanted kidney was rotated to a more vertical position in 3 pts. The radiation dose to the fetus is calculated at 0.024 rad/mCi administered. This study demonstrates the anatomic and physiologic alterations expected in the transplanted kidney during pregnancy when evaluated by renal scan and that the radiation burden may be acceptable in management of these pts.

  18. Early diagnosis of renal disease and renal failure.

    PubMed

    Lees, George E

    2004-07-01

    The main goal of early diagnosis of renal disease and renal failure in dogs and cats is to enable timely application of therapeutic interventions that may slow or halt disease progression. Strategies for early diagnosis of renal disease use urine tests that detect proteinuria that is a manifestation of altered glomerular permselectivity or impaired urine-concentrating ability as well blood tests to evaluate plasma creatinine concentration. Animals with progressive renal disease should be carefully investigated and treated appropriately. Animals with mild, possibly nonprogressive, renal disease should be monitored adequately to detect any worsening trends,which should lead to further investigation and treatment even if the increments of change are small. PMID:15223206

  19. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma. PMID:19266088

  20. UNITED STATES RENAL DATA SYSTEM

    EPA Science Inventory

    The United States Renal Data System (USRDS) is a national data system that collects, analyzes, and distributes information about end-stage renal disease (ESRD) in the United States. The USRDS is funded directly by the National Institute of Diabetes and Digestive and Kidney Diseas...

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

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  2. Renal failure after ruptured aneurysm.

    PubMed

    Abbott, W M; Abel, R M; Beck, C H; Fischer, J E

    1975-09-01

    The effectiveness of an intravenous nutritional program plus aggressive dialysis was studied in 32 patients with renal failure following ruptured abdominal aortic aneurysm. Each patient was managed postoperatively with a renal failure fluid regimen, consisting of the eight essential amino acids plus dextrose in conjunction with peritoneal dialysis and hemodialysis. This regimen induced salutary metabolic effects temporarily improving the patient's condition in most instances. No technical or septic complications associated with the intravenous dietary therapy occurred. However, the incidence of recovery of renal function was low, and the overall patient survival was only 12.5%. The experience indicates that although this program has been shown to be efficacious in some patients with acute renal failure, it seems of little benefit in those whose renal failure follows ruptured aortic aneurysm. PMID:808197

  3. Renal biopsy: methods and interpretation.

    PubMed

    Vaden, Shelly L

    2004-07-01

    Renal biopsy most often is indicated in the management of dogs and cats with glomerular disease or acute renal failure. Renal biopsy can readily be performed in dogs and cats via either percutaneous or surgical methods. Care should be taken to ensure that proper technique is used. When proper technique is employed and patient factors are properly addressed, renal biopsy is a relatively safe procedure that minimally affects renal function. Patients should be monitored during the post biopsy period for severe hemorrhage, the most common complication. Accurate diagnosis of glomerular disease, and therefore, accurate treatment planning,requires that the biopsy specimens not only be evaluated by light microscopy using special stains but by electron and immunofluorescent microscopy. PMID:15223207

  4. Renal Denervation: Where to Now?

    PubMed

    Wimmer, Neil J; Mauri, Laura

    2015-12-01

    Resistant hypertension remains a growing problem worldwide. Renal sympathetic denervation was thought to be a new method for the treatment for resistant hypertension. Early studies demonstrated a marked benefit in patients who underwent renal denervation procedures, but the pivotal SYMPLICITY 3-HTN trial, the only sham-controlled randomized trial performed, did not show a benefit for patients treated with the procedure compared to sham. There is still much to learn about the physiology and anatomy of renal sympathetic pathways as well as careful attention to medication adherence in order to understand the role of renal sympathetic denervation in treating hypertensive patients. While renal denervation technology remains available in clinical practice outside of the USA, we expect further development of this technology in the upcoming years and the continued evaluation of this technology in patients with hypertension as well as other disease states to fully understand its role. PMID:26482759

  5. Transatlantic link

    NASA Astrophysics Data System (ADS)

    (left) European Geophysical Society (EGS) President Rolf Meissner at AGU Headquarters with (center) Executive Director Fred Spilhaus and (right) Foreign Secretary Juan Roederer. Meissner attended the meeting of AGU's Committee on International Participation (CIP) on February 26, 1988. At that meeting, specific ways of fostering close links between AGU and EGS were discussed.A few weeks later, Roederer and AGU staff, working with EGS Secretary-General Arne Richter at the EGS meeting in Bologna, Italy, March 21-25, planned details of the establishment of an AGU office in Europe. The Copernicus Gesellschaft, a new entity located on the premises of the Max Planck Institute for Aeronomy in Lindau, Federal Republic of Germany, will provide the administrative staff and handle logistics.

  6. Renal transplantation in infants.

    PubMed

    Jalanko, Hannu; Mattila, Ilkka; Holmberg, Christer

    2016-05-01

    Renal transplantation (RTx) has become an accepted mode of therapy in infants with severe renal failure. The major indications are structural abnormalities of the urinary tract, congenital nephrotic syndrome, polycystic diseases, and neonatal kidney injury. Assessment of these infants needs expertise and time as well as active treatment before RTx to ensure optimal growth and development, and to avoid complications that could lead to permanent neurological defects. RTx can be performed already in infants weighing around 5 kg, but most operations occur in infants with a weight of 10 kg or more. Perioperative management focuses on adequate perfusion of the allograft and avoidance of thrombotic and other surgical complications. Important long-term issues include rejections, infections, graft function, growth, bone health, metabolic problems, neurocognitive development, adherence to medication, pubertal maturation, and quality of life. The overall outcome of infant RTx has dramatically improved, with long-term patient and graft survivals of over 90 and 80 %, respectively. PMID:26115617

  7. Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

    PubMed Central

    Gong, Yongfeng; Himmerkus, Nina; Plain, Allein; Bleich, Markus

    2015-01-01

    The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney—claudin-14, -16, and -19—as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases. PMID:25071082

  8. Renal disease and chronic renal failure in dental practice.

    PubMed

    Fitzpatrick, J J; Wilson, M H; McArdle, N S; Stassen, L F A

    2008-01-01

    Patients with renal diseases are increasingly common in dental practice. This is due to advances in medicine, and the increasing life expectancy of western populations. Chronic renal failure is a serious condition that general dental practitioners may see in their practice. This article discusses the functions of the kidney, and the causes and medical management of chronic renal failure, as well as considerations in the dental management of these patients. Common complications such as infection and bleeding are discussed. General recommendations are made, based on current evidence with respect to prescribing of medications. PMID:18986093

  9. Atheroembolic renal disease

    MedlinePlus

    ... of the kidneys. Causes AERD is linked to atherosclerosis . Atherosclerosis is a common disorder of the arteries. It ... blockages of the kidney blood vessels are severe. Atherosclerosis of the aorta is the most common cause ...

  10. SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2.

    PubMed

    Reiche, Juliane; Theilig, Franziska; Rafiqi, Fatema H; Carlo, Anne-Sophie; Militz, Daniel; Mutig, Kerim; Todiras, Mihail; Christensen, Erik Ilsø; Ellison, David H; Bader, Michael; Nykjaer, Anders; Bachmann, Sebastian; Alessi, Dario; Willnow, Thomas E

    2010-06-01

    Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor with A-type repeats) in functional activation of renal ion transporters. We demonstrate that SORLA is expressed in epithelial cells of the thick ascending limb (TAL) of Henle's loop and that lack of receptor expression in this cell type in SORLA-deficient mice results in an inability to properly reabsorb sodium and chloride during osmotic stress. The underlying cellular defect was correlated with an inability of the TAL to phosphorylate Na(+)-K(+)-Cl(-) cotransporter 2 (NKCC2), the major sodium transporter in the distal nephron. SORLA functionally interacts with Ste-20-related proline-alanine-rich kinase (SPAK), an activator of NKCC2, and receptor deficiency is associated with missorting of SPAK. Our data suggest a novel regulatory pathway whereby intracellular trafficking of SPAK by the sorting receptor SORLA is crucial for proper NKCC2 activation and for maintenance of renal ion balance. PMID:20385770

  11. Characteristics of taurine transport in cultured renal epithelial cell lines: asymmetric polarity of proximal and distal cell lines.

    PubMed

    Jones, D P; Miller, L A; Budreau, A; Chesney, R W

    1992-01-01

    Taurine transport was determined in two continuous, renal epithelial cell lines: LLC-PK1 derived from the proximal tubule of the pig, and the Madin-Darby canine kidney cell (MDCK) from the distal tubule of the dog. In LLC-PK1, taurine transport is maximal at the apical surface, whereas in MDCK cells, transport is greatest at the basolateral surface. Transport is highly dependent on both sodium and chloride in the external medium, and is specific for beta-amino acids. The apical and basolateral surfaces of both cell lines show an adaptive response to extracellular taurine concentration, but only the basolateral surface of the MDCK cell responds to hyperosomolality by increased taurine accumulation. Thus, differential control of the beta-amino acid transport system by substrate and external tonicity exists. The role of the beta-amino acid transport system may differ according to the origin of the cell: in the proximal renal tubular cell, net transepithelial reabsorption of filtered taurine increases the body pool. By contrast, taurine accumulation by distal tubular cells may form a mechanism of cell volume regulation in response to osmotic stress. PMID:1509959

  12. Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

    PubMed Central

    Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

    2016-01-01

    Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

  13. Developmental Signaling: Does It Bridge the Gap Between Cilia Dysfunction and Renal Cystogenesis?

    PubMed Central

    Tran, Pamela V.; Sharma, Madhulika; Li, Xiaogang; Calvet, James P.

    2015-01-01

    For more than a decade, evidence has accumulated linking dysfunction of primary cilia to renal cystogenesis, yet molecular mechanisms remain undefined. The pathogenesis of renal cysts is complex, involving multiple cellular aberrations and signaling pathways. Adding to this complexity, primary cilia exhibit multiple roles in a context-dependent manner. On renal epithelial cells, primary cilia act as mechanosensors and trigger extracellular Ca2+ influx in response to laminar fluid flow. During mammalian development, primary cilia mediate the Hedgehog (Hh), Wnt, and Notch pathways, which control cell proliferation and differentiation, and tissue morphogenesis. Further, experimental evidence suggests the developmental state of the kidney strongly influences renal cystic disease. Thus, we review evidence for regulation of Ca2+ and cAMP, key molecules in renal cystogenesis, at the primary cilium, the role of Hh, Wnt, and Notch signaling in renal cystic disease, and the interplay between these developmental pathways and Ca2+ signaling. Indeed if these developmental pathways influence renal cystogenesis, these may represent novel therapeutic targets that can be integrated into a combination therapy for renal cystic disease. PMID:24861210

  14. Renal Glucose Handling

    PubMed Central

    Ferrannini, Ele; Veltkamp, Stephan A.; Smulders, Ronald A.; Kadokura, Takeshi

    2013-01-01

    OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to <90), moderate (eGFR3 ≥30 to <60), or severe reduction in eGFR (eGFR4 ≤15 to <30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment. PMID:23359360

  15. Patterning the Renal Vascular Bed

    PubMed Central

    Herzlinger, Doris; Hurtado, Romulo

    2015-01-01

    The renal vascular bed has a stereotypic architecture that is essential for the kidney’s role in excreting metabolic waste and regulating the volume and composition of body fluids. The kidney’s excretory functions are dependent on the delivery of the majority of renal blood flow to the glomerular capillaries, which filter plasma removing from it metabolic waste, as well as vast quantities of solutes and fluids. The renal tubules reabsorb from the glomerular filtrate solutes and fluids required for homeostasis, while the post-glomerular capillary beds return these essential substances back into the systemic circulation. Thus, the kidney’s regulatory functions are dependent on the close proximity or alignment of the post-glomerular capillary beds with the renal tubules. This review will focus on our current knowledge of the mechanisms controlling the embryonic development of the renal vasculature. An understanding of this process is critical for developing novel therapies to prevent vessel rarefaction and will be essential for engineering renal tissues suitable for restoring kidney function to the ever-increasing population of patients with end stage renal disease. PMID:25128732

  16. Effects of supplemental recombinant bovine somatotropin and mist-fan cooling on the renal tubular handling of sodium in different stages of lactation in crossbred Holstein cattle.

    PubMed

    Boonsanit, Dolrudee; Chanpongsang, Somchai; Chaiyabutr, Narongsak

    2012-08-01

    The effect of supplementary administration of recombinant bovine somatotrophin (rbST) on the renal tubular handling of sodium in crossbred 87.5% Holstein cattle housed in normal shade (NS) or mist-fan cooled (MF) barns was evaluated. The cows were injected with 500 mg rbST at three different stages of lactation. The MF barn housed cows showed a slightly decreased ambient temperature and temperature humidity index, but an increased relative humidity. Rectal temperature and respiration rates were significantly lower in cooled cows. The rbST treated cows, housed in NS or MF barns, showed markedly increased milk yields, total body water, extracellular fluid and plasma volume levels, along with a reduced rate of urine flow and urinary excretion of sodium, potassium and chloride ions and osmolar clearance, in all three stages of lactation. Renal tubular sodium and water reabsorption were increased after rbST administration without any alteration in the renal hemodynamics. Lithium clearance data suggested that the site of response is in the proximal nephron segment, which may be mediated via increases in the plasma levels of aldosterone and IGF-1, but not vasopressin, during rbST administration. PMID:21862090

  17. Cardiovascular risk factors following renal transplant

    PubMed Central

    Neale, Jill; Smith, Alice C

    2015-01-01

    Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. PMID:26722646

  18. Urinary Calprotectin and Posttransplant Renal Allograft Injury

    PubMed Central

    Bistrup, Claus; Marcussen, Niels; Pagonas, Nikolaos; Seibert, Felix S.; Arndt, Robert; Zidek, Walter; Westhoff, Timm H.

    2014-01-01

    Objective Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. Methods In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. Results We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. Conclusions Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation. PMID:25402277

  19. Renal Ablation Update

    PubMed Central

    Khiatani, Vishal; Dixon, Robert G.

    2014-01-01

    Thermal ablative technologies have evolved considerably in the recent past and are now an important component of current clinical guidelines for the treatment of small renal masses. Both radiofrequency ablation and cryoablation have intermediate-term oncologic control that rivals surgical options, with favorable complication profiles. Studies comparing cryoablation and radiofrequency ablation show no significant difference in oncologic control or complication profile between the two modalities. Early data from small series with microwave ablation have shown similar promising results. Newer technologies including irreversible electroporation and high-intensity–focused ultrasound have theoretical advantages, but will require further research before becoming a routine part of the ablation armamentarium. The purpose of this review article is to discuss the current ablative technologies available, briefly review their mechanisms of action, discuss technical aspects of each, and provide current data supporting their use. PMID:25049445

  20. [Cystic renal pathology].

    PubMed

    Rosi, P; Cesaroni, M; Bracarda, S; Rociola, W; Virgili, G

    1993-08-01

    Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID:8353538

  1. Renal ablation update.

    PubMed

    Khiatani, Vishal; Dixon, Robert G

    2014-06-01

    Thermal ablative technologies have evolved considerably in the recent past and are now an important component of current clinical guidelines for the treatment of small renal masses. Both radiofrequency ablation and cryoablation have intermediate-term oncologic control that rivals surgical options, with favorable complication profiles. Studies comparing cryoablation and radiofrequency ablation show no significant difference in oncologic control or complication profile between the two modalities. Early data from small series with microwave ablation have shown similar promising results. Newer technologies including irreversible electroporation and high-intensity-focused ultrasound have theoretical advantages, but will require further research before becoming a routine part of the ablation armamentarium. The purpose of this review article is to discuss the current ablative technologies available, briefly review their mechanisms of action, discuss technical aspects of each, and provide current data supporting their use. PMID:25049445

  2. [Cilia and renal cysts].

    PubMed

    Paces-Fessy, Mélanie

    2014-11-01

    Advances in genomics, bioinformatics and the creation of model organisms have identified many genes associated with polycystic kidney diseases. Historically, these genes were not necessarily associated with ciliopathies, but it appeared that many connections can be made between the cystic kidney disease and function of the primary cilium. Indeed, the proteins encoded by these genes are localized to the cilium itself, to the basal body or are known to regulate the expression and localization of ciliary proteins. The goal of this article is to describe the multiple cellular processes that may lead to the development of renal cysts if they are deregulated. These include changes in proliferation rate, cell polarity or signaling pathways involved in embryonic kidney development. To highlight the role of the primary cilium in cystogenesis, I will discuss several studies investigating the function of ciliary genes and cilia in the kidneys of different model organisms. PMID:25388585

  3. Hyperparathyroidism of Renal Disease

    PubMed Central

    Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J

    2016-01-01

    Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1.73 m2). Since the 1990s, improving medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs has expanded the treatment options for patients with rHPT, but some patients still require a parathyroidectomy to mitigate the sequelae of this challenging disease. PMID:27479950

  4. Renal Cancer in the Elderly.

    PubMed

    González León, Tania; Morera Pérez, Maricela

    2016-01-01

    The increase of the aging population corresponds with the rise of renal cancer in elderly patients. The distinction between functional and chronological age, quality of life, and survival estimate are important issues, among others, that should be considered in the management of renal cancer in elderly patients. We made this review with the purpose of synthesizing the most updated criteria regarding indications and outcomes of the different therapeutic options in the management of elderly patients with renal cancer, beginning from the physiologic considerations that characterize them, their capacity to tolerate different therapeutic possibilities, and the prognosis of the patients' risks and comorbidity assessment. PMID:26715222

  5. Unusual renal tumour: multilocular cystic renal cell carcinoma.

    PubMed

    Palmeiro, Marta Morna; Niza, João Luz; Loureiro, Ana Luisa; Conceição e Silva, João Paulo

    2016-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a rare presentation of renal cell carcinoma. Most patients are asymptomatic and frequently MCRCCs are detected incidentally. MCRCCs have good prognosis because of their low malignant potential. We report a case of a 39-year-old woman who presented with mild right flank pain and normal laboratory data. On imaging examinations, a Bosniak III cystic lesion was detected in the lower third of the right kidney. She underwent right partial nephrectomy and histopathology showed a multilocular cystic renal cell carcinoma Fuhrman grade 1. In this article, we also present a review of the literature on MCRCC, highlight the correlation of the pathological and imaging characteristics of these low aggressive renal lesions, and underscore the importance of their recognition to prevent unnecessary radical surgery. PMID:26957035

  6. Hypohyperparathyroidism: a model for renal osteodystrophy?

    PubMed

    Junor, B J; Edward, N

    1981-06-01

    A child who presented with features of renal osteodystrophy but with normal renal function is described. Improvement occurred both on large doses of vitamin D and small doses of 1, alpha-hydroxy-vitamin D3 (1, alpha-OHD3). Investigations suggested that the primary defect was an impaired renal response to parathyroid hormone. The relationship between renal osteodystrophy, abnormalities of vitamin D metabolism and hypohyperparathyroidism is discussed and an alternative hypothesis for the development of renal bone disease suggested. PMID:7301683

  7. Chemerin in renal dysfunction and cardiovascular disease.

    PubMed

    Bonomini, Mario; Pandolfi, Assunta

    2016-02-01

    The potential involvement of chemerin in cardiovascular and renal dysfunction has recently been acknowledged. There are indeed many links between this protein and inflammation, atherosclerosis, and multiple obesity- and diabetes-related parameters such as body mass index, insulin resistance, and blood levels of insulin, cholesterol, triglycerides, and glucose. In addition, in the last few years, several reports have investigated the circulating chemerin levels and their pathophysiologic significance in chronic kidney disease populations. However, there are still gaps in our understanding of this matter, in particular as to whether elevated chemerin might be the cause behind, or simply mirror, a reduced renal function. The limitations of the present knowledge on chemerin may partly relate to the lack of specific antibodies for assessing the different active isoforms of the protein. Measuring its bioactive serum concentration, and achieving a precise overall pattern of the tissue-specific formation of different isoforms, with the use of suitable technology, will ultimately help define the role of chemerin in disease pathophysiology, or as a diagnostic or therapeutic marker. PMID:26545628

  8. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

    PubMed Central

    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  9. Renal function in suckling and fasting pups of the northern elephant seal.

    PubMed

    Houser, D S; Crocker, D E; Webb, P M; Costa, D P

    2001-06-01

    Elephant seals fast for prolonged periods without access to water. This is made possible, in part, by reductions in urine production. However, the mechanisms involved in reducing urine production are not understood. In this study, glomerular filtration rate (GFR) was measured in five northern elephant seal pups (Mirounga angustirostris) via the inulin clearance technique. Measurements were made during day 9 and day 18-22 of nursing and the second and eighth week of the postweaning fast. Plasma aldosterone and cortisol concentrations, quantified by radioimmunoassay, were measured in eight other weanlings during the second and eighth week of the fast. Mean GFR was 79.3+/-29.3 ml/min during the early suckling period and 78.2+/-17.1, 89.8+/-52.7, and 80.4+/-12.2 ml/min during the late suckling, early fasting and late fasting periods, respectively. Differences between nursing and fasting were insignificant, possibly because reduced protein oxidation during suckling and rapid recruitment of protein for tissue synthesis obviated the need for postprandial hyperfiltration. Alternatively, maintenance of GFR during fasting may facilitate urea concentration by compensating for reductions in the fractional excretion of urea. It is further hypothesized that aldosterone is primarily responsible for mediating renal water reabsorption in this system. PMID:11423313

  10. Resolving an 80-yr-old controversy: the beginning of the modern era of renal physiology.

    PubMed

    Jamison, Rex L

    2014-12-01

    Marcello Malpighi discovered the glomerulus that bears his name in the 17th century, but it was not until the middle of the 19th century, in 1842, that William Bowman in London published his studies of the histological structure of the glomerulus and proposed that urine formation begins with glomerular secretion. At nearly the same time in Marburg, Carl Ludwig, unaware of Bowman's findings, proposed that urine formation begins with glomerular filtration followed by tubule reabsorption. The controversy lasted 80 yr. Prominent investigators weighed in on both sides. Rudolph Heidenhain's findings in 1874 swung the pendulum toward Bowman's theory until Arthur Cushny published his book, The Secretion of Urine, in 1917, in which he found the evidence insufficient to prove either theory. In 1921, a young physician, Joseph Wearn, began his postresidency training in the laboratory of Alfred N. Richards. He read Cushny's book and learned how to expose the glomerulus of a living frog. Richards proposed that Wearn use that experimental preparation to inject epinephrine into the glomerulus. Wearn proposed a different experiment: instead of using injection, collect fluid from the glomerulus and analyze it. Richards agreed, and the landmark results of that experiment, published in 1924, settled the controversy. The modern era of renal physiology was born. PMID:25434011

  11. Renal function and structure in a rat model of arterial calcification and increased pulse pressure.

    PubMed

    Gaillard, Virginie; Jover, Bernard; Casellas, Daniel; Cordaillat, Magali; Atkinson, Jeffrey; Lartaud, Isabelle

    2008-10-01

    Clinical studies suggest a strong link between tissue calcification and pressure hyperpulsatility in end stage renal disease patients. Using a Wistar rat model of arterial elastocalcinosis and hyperpulsatility [vitamin D and nicotine (VDN) treatment], we evaluated the relative importance of tissue calcification and hyperpulsatility in the etiology of renal failure. VDN rats showed significant increases in aortic wall calcium content (50 times; 992+/-171 vs. control 19+/-1 micromol/g dry wt) and pulse pressure (1.5 times; 61+/-4 vs. control 40+/-2 mmHg). Significant renal calcification (16 times; 124+/-27 vs. control 8.1+/-0.7 micromol/g dry wt) occurred mainly within the media of the preglomerular vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal damages (5 times; 26+/-5% of collapsed-atrophic or sclerotic glomeruli, or glomerular cysts vs. control 5.2+/-0.3%; 28 times; 61+/-12% areas of focal, cortical areas exhibiting interstitial fibrosis per section vs. control 2.2+/-0.6%) were observed histologically. The glomerular filtration rate significantly decreased (880+/-40 vs. control 1,058+/-44 microl.min(-1).g kidney wt(-1)). Albuminuria increased six times (1.6+/-0.4 vs. control 0.27+/-0.04 mg/24 h). There were significant linear relationships between albuminuria and pulse pressure (r2=0.408; n=24) or renal calcium content (r2=0.328; n=24; P<0.05) and between glomerular filtration rate and pulse pressure (r2=0.168; n=27). To our knowledge, this study provides the first evidence of links between both 1) hyperpulsatility and renal dysfunction, and 2) renal calcification and renal dysfunction. Given the increasing frequency of end-stage renal disease, this model could prove useful for preclinical evaluation of drugs that prevent or attenuate hyperpulsatility and/or tissue calcification. PMID:18715942

  12. Urea distribution in renal failure

    PubMed Central

    Blackmore, D. J.; Elder, W. J.; Bowden, C. H.

    1963-01-01

    An assessment of intracellular urea removed during haemodialysis has been made from urea extraction and plasma urea estimations. An apparent wide variation in the movement of intracellular urea in patients with acute renal failure from obstetric and traumatic causes and with chronic renal failure is reported. A method for the estimation of red cell water urea is presented. In two patients with chronic renal failure the red cell urea level was much higher than would have been expected from the plasma urea level before dialysis. In two obstetric patients there was no such discrepancy. The conclusion is drawn that research should be directed to variations of intracellular metabolism in renal failure before a more rational approach can be made to its management. PMID:16811009

  13. The renal mononuclear phagocytic system.

    PubMed

    Nelson, Peter J; Rees, Andrew J; Griffin, Matthew D; Hughes, Jeremy; Kurts, Christian; Duffield, Jeremy

    2012-02-01

    The renal mononuclear phagocytic system, conventionally composed of macrophages (Mø) and dendritic cells (DCs), plays a central role in health and disease of the kidney. Overlapping definitions of renal DCs and Mø, stemming from historically separate research tracks and the lack of experimental tools to specifically study the roles of these cells in vivo, have generated confusion and controversy, however, regarding their immunologic function in the kidney. This brief review provides an appraisal of the current state of knowledge of the renal mononuclear phagocytic system interpreted from the perspective of immunologic function. Physical characteristics, ontogeny, and known functions of the main subsets of renal mononuclear phagocytes as they relate to homeostasis, surveillance against injury and infection, and immune-mediated inflammatory injury and repair within the kidney are described. Gaps and inconsistencies in current knowledge are used to create a roadmap of key questions to be answered in future research. PMID:22135312

  14. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  15. Renal protection in cardiovascular surgery

    PubMed Central

    Di Tomasso, Nora; Monaco, Fabrizio; Landoni, Giovanni

    2016-01-01

    Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided. PMID:26998249

  16. Primary carcinoma of renal calyx.

    PubMed

    Williams, Phillip A; Mai, Kien T

    2013-10-01

    Renal calyx carcinoma (RCXC) may mimic collecting duct carcinoma (CDC) or urothelial carcinoma (UC) of the renal pelvis. RCXC is distinguished from CDC and UC of the renal pelvis as having the tumor epicenter in the renal calyx, with limited involvement of the surrounding renal pelvis surface urothelium. In this study, we summarize our experience with this entity. Ten cases of RCXC, including 9 cases with urothelial differentiation (RCXC-UC) and 1 case with salivary gland-type differentiation (RCXC-SC), were identified. Ten consecutive cases of UC were selected for comparison, with extensive renal pelvis involvement and with secondary renal parenchymal invasion. Two cases of collecting duct carcinoma (CDC) were also examined. Immunohistochemistry (IHC) was performed on representative tissue blocks for PAX8, PAX2, CK5, CK7, CK20, p63, GATA3, AMACR, RCC, CD10, vimentin, S100, and MSA. The 10 cases of RCXC (M:F=4:6, ages: 62-91 years, mean: 76) presented with renal masses of 3-6cm. Ureteroscopic studies and renal pelvic washings showed atypical/malignant cells in three cases. Seven patients were treated with nephrectomy followed by radiation±chemotherapy, and all cases developed metastases to lymph nodes or liver/lung/bone. In all 7 cases with nephrectomy, there was extensive renal parenchymal involvement with infiltrating borders and diffuse spread along collecting ducts. Six RCXC-UC contained focal squamous differentiation. The RCXC-SC displayed features of adenoid cystic and basaloid features. In situ UC, with or without papillary components, was identified in the calyces in all 7 nephrectomy cases with remaining renal pelvis harboring small tumor burden in 5 cases, and no tumor in another 2 cases. Of the three cases without nephrectomy, no tumor in the renal pelvis could be visualized with endoscopy, however one case was associated with UC of the urinary bladder. Of 10 control UC cases, tumor was limited to the tip of renal papilla in 7 cases, extensive in 3

  17. Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

    ClinicalTrials.gov

    2015-12-23

    Chronic Allograft Nephropathy; Chronic Kidney Disease; Chronic Renal Failure; Disordered Mineral Metabolism; End Stage Renal Disease; Hyperparathyroidism; Hypophosphatemia; Kidney Disease; Kidney Transplantation; Post Renal Transplantation

  18. Cystic renal neoplasms and renal neoplasms associated with cystic renal diseases in adults: cross-sectional imaging findings.

    PubMed

    Katabathina, Venkata S; Garg, Deepak; Prasad, Srinivasa R; Vikram, Raghu

    2012-01-01

    Cystic renal neoplasms in adults are a heterogeneous group of tumors with characteristic histogenesis, pathological findings, and variable biological profiles. They include disparate entities that are either biologically benign (lymphangioma, cystic nephroma, and mixed epithelial and stromal tumor) or malignant (cystic renal cell carcinoma, multilocular cystic renal cell carcinoma, and primary renal synovial sarcoma). Renal cystic diseases are characterized by cystic changes of the kidneys due to hereditary, developmental, or acquired etiology. Cystic renal diseases such as acquired cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis are associated with the development of a wide spectrum of benign and malignant renal neoplasms. Most cystic renal tumors and cystic disease-associated renal neoplasms show characteristic cross-sectional imaging findings that permit accurate diagnosis. In addition, cross-sectional imaging is pivotal in the follow-up and surveillance of adult cystic tumors of the kidney. PMID:23192202

  19. Metoclopramide and renal vascular resistance.

    PubMed

    Manara, A R; Bolsin, S; Monk, C R; Hartnell, G; Harris, R A

    1991-01-01

    We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide. PMID:1997046

  20. Management of acute renal failure

    PubMed Central

    Fry, A C; Farrington, K

    2006-01-01

    Acute renal failure is a common condition, frequently encountered in both community practice and hospital inpatients. While it remains a heterologous condition, following basic principles makes investigation straightforward, and initial management follows a standard pathway in most patients. This article shows this, advises on therapeutic strategies, including those in special situations, and should help the clinician in deciding when to refer to a nephrologist, and when to consider renal replacement therapy. PMID:16461473

  1. Oxygen radicals and renal diseases.

    PubMed

    Klahr, S

    1997-01-01

    Reactive oxygen metabolites (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorous acid) are important mediators of renal damage in acute renal failure and glomerular and tubulointerstitial diseases. The role of these oxygen metabolites in the above entities is discussed, and the effects of antioxidants and scavengers of O2 radicals are considered. The role of oxygen radicals in the regulation of gene transcription is also considered. PMID:9387104

  2. [Renal injury in Takayasu's arteritis].

    PubMed

    Boubaker, Karima; Kaaroud, Hayet; Goucha, Rim; Kheder, Adel

    2014-11-01

    Renal involvement in Takayasu's arteritis is frequent and worsens the progression of the disease. This is primarily a renal artery stenosis causing renovascular hypertension. The glomerular disease is exceptional. This study was undertaken to determine the clinical, radiological, biological features and therapeutic response in patients with kidney disease associated with Takayasu arteritis. A retrospective chart review was conducted on 11 patients (five men and six females), with a mean age of 31.1 years (19-40 years). The discovery of kidney disease preceded the diagnosis of Takayasu's arteritis in eight cases. Ten patients developed hypertension. Laboratory finding showed proteinuria in five cases of which one case was due to nephrotic syndrome. Renal failure was found in six cases including four cases in stage of terminal chronic renal failure. Impairment of the renal artery was present in nine patients, proximal in seven cases and distal in two cases, bilateral in five cases and unilateral in four cases. Narrowing renal artery was found in seven cases. The renal biopsy revealed membranoproliferative glomerulonephritis in one case and nephrosclerosis in another case. Eleven patients were followed for an average period of 155 months (3-335 months). Remission of nephrotic syndrome was concomitant with the remission of the disease. Seven patients developed outbreaks of Takayasu's arteritis of which six were in care. Relapse of nephrotic syndrome was concomitant with the outbreak of the disease followed by spontaneous remission of both diseases. Improved pressure was obtained in 5 cases and worsening renal function in seven cases. Death was observed in two cases. PMID:25440941

  3. Renal Ammonia Metabolism and Transport

    PubMed Central

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  4. Sex-linked dominant

    MedlinePlus

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... one of the sex chromosomes, which are the X and Y chromosomes. Dominant inheritance occurs when an ...

  5. Sex-linked recessive

    MedlinePlus

    Inheritance - sex-linked recessive; Genetics - sex-linked recessive; X-linked recessive ... X-linked recessive diseases usually occur in males. Males have only one X chromosome. A single recessive ...

  6. Sex-linked dominant

    MedlinePlus

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... type of chromosome that is affected (autosomal or sex chromosome). It also depends on whether the trait ...

  7. Renal and systemic acid-base effects of chronic dichloroacetate administration in dogs.

    PubMed

    Hulter, H N; Glynn, R D; Sebastian, A

    1980-10-01

    Dichloroacetate (DCA) increases metabolic disposal of lactic acid secondary to activation of pyruvate dehydrogenase and consequent acceleration of pyruvate oxidation. DCA has thus been proposed as a therapeutic agent for clinical states of lactic acidosis. Yet, DCA has a potential metabolic acidosis-producing effect by virtue of reported effects of (A) increasing blood ketoacid concentration, (B) decreasing tubular reabsorption of filtered ketoacid anions, and (C) decreasing renal NH3 production. In the present study chronic administration of DCA, 50 mg/kg p.o. daily for 6-8 days, resulted in a cumulative increase in renal net acid excretion (NAE) (sigma delta NAE, +61 meq, p < 0.05). The increase in NAE was accounted for entirely by increased NH4+ excretion. Production of ammonia by the kidney appeared to be increased since the increased excretion of NH4+ was accompanied by an increase in urine pH (delta UpH, +0.18 +/- 0.07, p < 0.05). The increase in NAE was accompanied by a nearly identical increase in urinary anion gap (UAG) (UAG = [NH4+ + Na+ + K+] - [Cl- + HCO3- + HPO4(2-) + H2PO4-]). The increase in UAG was caused by increased urinary total organic anions, accounted for at least in part by a significant increase in urinary acetoacetate. No significant increase in urinary potassium or sodium excretion occurred. A change in plasma acid-base composition occurred that was consistent with a mild respiratory acidosis without associated primary metabolic acidosis or alkalosis. These findings indicate that chronic DCA administration results in (1) increased steady state endogenous noncarbonic organic acid production, and (2) retention of carbonic acid. Further investigation of the potential metabolic and respiratory acidosis-producing effects of DCA is required to determine its clinical efficacy in the treatment of clinical lactic acidosis. PMID:7421587

  8. Renal artery injury during robot-assisted renal surgery.

    PubMed

    Lee, Jae Won; Yoon, Young Eun; Kim, Dae Keun; Park, Sung Yul; Moon, Hong Sang; Lee, Tchun Yong

    2010-07-01

    Laparoscopic partial nephrectomy (LPN) is becoming the standard of care for incidentally diagnosed, small renal tumors. With its seven degrees of freedom and three-dimensional vision, the DaVinci robotic surgical system has been used to assist in LPNs. The main disadvantage of robot-assisted surgery, however, is the lack of tactile feedback. We present a case of renal artery injury during robot-assisted renal surgery. Robot-assisted partial nephrectomy (RPN) was planned for 47-year-old man with a 3.5-cm right renal mass. After standard bowel mobilization, renal hilar dissection was performed. In the attempt to complete the dissection posteriorly, however, there was sudden profuse bleeding. The intraperitoneal pressure immediately increased to 20 mm Hg, and an additional suction device was inserted through the 5-mm liver retractor port. On inspection, there was an injury at the takeoff of the posterior segmental artery. A decision was made to convert to robot-assisted laparoscopic radical nephrectomy. The main renal artery and renal vein were controlled with Hem-o-Lok clips. The estimated blood loss was 2,000 mL. Four units of packed red blood cells were transfused intraoperatively. The post-transfusion hemoglobin level was 12.6 g/dL. There were no other perioperative complications. The surgeon should keep in mind that the robotic arms are very powerful and can easily injure major vessels because of lack of tactile feedback. A competent and experienced tableside surgeon is very important in robot-assisted surgery because the unsterile console surgeon cannot immediately react to intraoperative complications. PMID:20590468

  9. Pathophysiology and management of progressive renal disease.

    PubMed

    Brown, S A; Crowell, W A; Brown, C A; Barsanti, J A; Finco, D R

    1997-09-01

    Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats. PMID:9308397

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

    PubMed Central

    Bobulescu, Ion Alexandru; Moe, Orson W.

    2013-01-01

    In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible for 60–70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. In spite of tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiology, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that specifically act on individual renal urate transporters for the treatment of hyperuricemia and gout. PMID:23089270

  11. Dietary acrylamide and risk of renal cell cancer.

    PubMed

    Mucci, Lorelei A; Lindblad, Per; Steineck, Gunnar; Adami, Hans-Olov

    2004-05-01

    The detection of acrylamide, classified as a probable human carcinogen, in commonly consumed foods created public health alarm. Thus far, only 2 epidemiologic studies have examined the effect of dietary acrylamide on cancer risk. Presently, we reanalyzed data from a large population-based Swedish case-control study of renal cell cancer. Food frequency data were linked with national food databases on acrylamide content, and daily acrylamide intake was estimated for participants. The risk of renal cell cancer was evaluated for intake of food items with elevated acrylamide levels and for total daily acrylamide dose. Adjusting for potential confounders, there was no evidence that food items with elevated acrylamide, including coffee (OR(highest vs. lowest quartile) = 0.7; 95% CI = 0.4-1.1), crisp breads (OR(highest vs. lowest quartile) = 1.0; 95% CI = 0.6-1.6) and fried potatoes (OR(highest vs. lowest quartile) = 1.1; 95% CI = 0.7-1.7), were associated with a higher risk of renal cell cancer risk. Furthermore, there was no association between estimated daily acrylamide intake through diet and cancer risk (OR(highest vs. lowest quartile) = 1.1; 95% CI = 0.7-1.8; p for trend = 0.8). The results of this study are in line with the 2 previous studies examining dietary acrylamide and suggest there is no association between dietary acrylamide and risk of renal cell cancer. PMID:14999788

  12. [Renal transplantation: ethical issues].

    PubMed

    Mamzer-Bruneel, Marie-France; Laforêt, Emmanuelle Grand; Kreis, Henri; Thervet, Éric; Martinez, Frank; Snanoudj, Renaud; Hervé, Christian; Legendre, Christophe

    2012-12-01

    One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context. PMID:23168353

  13. Renal cell carcinoma

    PubMed Central

    Gao, Jianjun; Rathmell, W Kimryn

    2014-01-01

    The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC. PMID:25385470

  14. The scintigraphic pattern of renal angiomyolipoma

    SciTech Connect

    Jaikishen, P.; Oster, Z.H.; Atkins, H.L. )

    1990-03-01

    The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.

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

    MedlinePlus

    ... Action Myoclonus - Renal Failure Syndrome 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 ...

  16. Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Hatcher, Lori I.

    2012-01-01

    Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia. PMID:22993067

  17. Chronic renal failure in a patient with Sotos syndrome due to autosomal dominant polycystic kidney disease.

    PubMed

    Cefle, K; Yildiz, A; Palanduz, S; Ozturk, S; Ozbey, N; Kylyçaslan, I; Colakoglu, S; Balci, C

    2002-05-01

    Sotos syndrome is characterised by accelerated growth, acromegalic appearance, mental retardation and social maladjustment. Most cases are sporadic, but familial cases have also been reported. We report a case of Sotos syndrome presenting with chronic renal failure due to autosomal dominant polycystic kidney disease (ADPKD). Ultrasonographic examination of the patient, his father and other family members revealed polycystic kidneys. Renal failure was present only in the Sotos case, who also had considerably larger cysts than other family members. We suggest that the underlying mechanism responsible from the somatic overgrowth in Sotos syndrome may also be linked with the development of larger cysts and earlier onset of renal failure in ADPKD. Although Sotos syndrome has been associated with urological abnormalities, chronic renal failure is very rare. To our knowledge, Sotos syndrome associated with ADPKD has not been reported before. PMID:12074220

  18. Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts

    SciTech Connect

    Sussman, S.; Cochran, S.T.; Pagani, J.J.; McArdle, C.; Wong, W.; Austin, R.; Curry, N.; Kelly, K.M.

    1984-01-01

    Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery.

  19. The role of renal biopsy in small renal masses

    PubMed Central

    Burruni, Rodolfo; Lhermitte, Benoit; Cerantola, Yannick; Tawadros, Thomas; Meuwly, Jean-Yves; Berthold, Dominik; Jichlinski, Patrice; Valerio, Massimo

    2016-01-01

    Renal biopsy is being increasingly proposed as a diagnostic tool to characterize small renal masses (SRM). Indeed, the wide adoption of imaging in the diagnostic workup of many diseases had led to a substantial increased incidence of SRM (diameter ≤4 cm). While modern ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) techniques have high sensitivity for detecting SRM, none is able to accurately and reliably characterize them in terms of histological features. This is currently of key importance in guiding clinical decision-making in some situations, and in these cases renal biopsy should be considered. In this review, we aim to summarize the technique, diagnostic performance, and predicting factors of nondiagnostic biopsy, as well as the future perspectives. PMID:26858784

  20. The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation

    PubMed Central

    Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

    2016-01-01

    Background The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. Methods WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Results Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt

  1. Polyoma (BK) virus associated urothelial carcinoma originating within a renal allograft five years following resolution of polyoma virus nephropathy.

    PubMed

    Salvatore, Steven P; Myers-Gurevitch, Patricia M; Chu, Stacy; Robinson, Brian D; Dadhania, Darshana; Seshan, Surya V

    2016-03-01

    A direct role for BK polyomavirus infection in malignant tumors of renal allografts and urinary tract is emerging. Case reports suggest a link between BK virus (BKV) reactivation and development of malignancy in renal allograft recipients. Herein we describe the first case of BKV positive invasive urothelial carcinoma within the renal allograft, presenting with chronic diarrhea and weight loss 5 years following resolution of BK viremia/nephropathy (BKVN). Unique to our case was the remote history of BK viremia/BKVN, rising titer of anti-HLA antibody and presence of renal limited urothelial carcinoma with microinvasion of malignant cells staining positive for SV40 large T antigen (T-Ag). These findings suggest that persistence of subclinical BKV infection within the renal allograft may play a role in the malignant transformation of epithelial cells. Patients with history of BKVN may be at risk for kidney and urinary tract malignancy despite resolution of BK viremia/BKVN. PMID:26709521

  2. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  3. Radiographic Kinetics of Sarcomatoid Renal Cell Carcinoma.

    PubMed

    Syed, Ali; Raval, Amar; Pridjian, Andrew; Birbe, Ruth; Trabulsi, Edouard J

    2016-07-01

    Renal cell carcinoma is a common entity often managed surgically with excellent survival benefits. We report a rare case of sarcomatoid renal cell carcinoma with aggressive growth kinetics after palliative resection captured radiographically. PMID:27041470

  4. General Information about Renal Cell Cancer

    MedlinePlus

    ... Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  6. Primary renal primitive neuroectodermal tumor

    PubMed Central

    Goel, V; Talwar, V; Dodagoudar, C; Singh, S; Sharma, A; Patnaik, N

    2015-01-01

    Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach. PMID:25766349

  7. Future challenges in renal transplantation.

    PubMed

    Whalen, H; Clancy, M; Jardine, A

    2012-02-01

    There is a worldwide increase in the incidence of end-stage renal disease. Renal transplantation has been shown to be cost effective, prolong survival and provide a better quality of life in comparison to dialysis. Consequently, there has been a steady increase in demand for organs leading to a shortage of available kidneys, and an increase in transplant waiting lists. Renal transplantation is therefore an expanding field with a number of unique future challenges to address. This article outlines strategies that may be employed to expand organ supply in order to meet increased demand. The ethical issues surrounding this are also summarized. Furthermore, we highlight techniques with the potential to minimize peri-transplant injury to the kidney on its journey from donor to recipient. Current and potential future management strategies to optimize graft and patient survival are also discussed. PMID:22361673

  8. Management of diabetic renal disease

    PubMed Central

    Eboh, Cecil

    2015-01-01

    Diabetic nephropathy is the leading cause of end stage renal failure (ESRF) worldwide, representing over 50% of patients on renal replacement therapy in some parts of the world. The condition is common in people with type 1 and type 2 diabetes, although the incidence appears to be declining, especially in type 1 diabetes. More than 1 in 3 people with type 2 diabetes have impaired kidney function. Advances in our understanding of the pathogenesis and natural history of the condition have enabled us to consider earlier therapy aimed at renal preservation and reduction in cardiovascular morbidity. Microalbuminuria is now established as the earliest risk marker for nephropathy in type 1 diabetes and cardiovascular disease in type 2 diabetes. This review examines the current concepts in the pathogenesis and management of diabetic nephropathy. PMID:26244141

  9. Parasites and chronic renal failure

    PubMed Central

    Mohammadi Manesh, Reza; Hosseini Safa, Ahmad; Sharafi, Seyedeh Maryam; Jafari, Rasool; Bahadoran, Mehran; Yousefi, Morteza; Nasri, Hamid; Yousofi Darani, Hossein

    2014-01-01

    Suppression of the human immune system results in an increase in susceptibility to infection by various infectious agents. Conditions such as AIDS, organ transplantation and chronic renal insufficiency (CRI) are the most important cause of insufficient immune response against infections. Long term renal disorders result in uremia, which can suppress human immune system. Parasitic infections are one of the most important factors indicating the public health problems of the societies. These infections can be more hostile and life threatening in susceptible individuals than in the normal people. In these patients some parasitic infections such as blastocystiosis, cryptosporidiosis and toxoplasmosis have been reported to be more prevalent. This review aimed to give an overview about parasitic infections in patients with renal disorders. PMID:25610885

  10. An unrecognized renal physiologist: Friedrich Wöhler.

    PubMed

    Richet, G

    1995-01-01

    Wöhler, in 1828, was the first chemist to synthesize urea. In 1824, towards the end of his medical studies, he had already published an important article on the renal excretion of some 41 substances administered orally or parenterally and on the links between their renal excretion and their metabolism: salts of potassium are excreted either reduced or oxidized, urine can be acidic when the blood is alkaline, the rate of water excretion is influenced by the rate of substances excreted in the same form as they are administered. He adumbrated the general concepts on the role of the kidney in the maintenance of the composition of the body. Had he continued in this direction, Wöhler would have been recognized not only as a remarkable chemist but also as a great physiologist. PMID:8546178

  11. [Carbonyl stress and oxidatively modified proteins in chronic renal failure].

    PubMed

    Bargnoux, A-S; Morena, M; Badiou, S; Dupuy, A-M; Canaud, B; Cristol, J-P

    2009-01-01

    Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis. PMID:19297289

  12. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases.

    PubMed

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

  13. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases

    PubMed Central

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

  14. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    PubMed

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function. PMID:26538440

  15. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. PMID:26360835

  16. Renal pelvis urothelial carcinoma of the upper moiety in complete right renal duplex: a case report

    PubMed Central

    Zhang, Yiran; Yu, Quanfeng; Zhang, Zhihong; Liu, Ranlu; Xu, Yong

    2015-01-01

    Urothelial carcinoma (UC) originated from renal pelvis is the common tumor of the urinary system, however, neoplasia of the renal pelvis in duplex kidneys is extremely rare, especially in the complete renal and ureteral duplex cases. We present the first case of renal pelvis UC of the upper moiety in a complete right renal duplex. This male patient has bilateral complete renal and ureteral duplex. To the best of our knowledge, this is the first reported case of renal pelvis UC in a complete renal duplex system. After this experience we feel that the diagnosis of renal pelvis UC in duplex kidneys is not so easy, and once the diagnosis is determined, the whole renal duplex units and bladder cuff or ectopic orifice should be excised radically. PMID:26823906

  17. Papillary adenocarcinoma of the renal pelvis with renal calculus: A rare case report

    PubMed Central

    LI, JIANLONG; LI, QING; YU, YI

    2016-01-01

    Papillary adenocarcinoma of the renal pelvis is a rare clinicopathology of a kidney tumor with renal calculus. In the present case report, percutaneous renal biopsy, nephroscope lithotripsy and radical nephroureterectomy within a papillary adenocarcinoma of the renal pelvis accompanied with renal calculus was performed on a 65-year-old patient, also including a report on the patient's data and a literature review. The histopathological features confirmed the diagnosis of papillary adenocarcinoma of the renal pelvis. Tumors of the renal pelvis are uncommon features of urothelial carcinoma, and papillary adenocarcinoma of the renal pelvis is a very unusual entity. The present case report describes papillary adenocarcinoma of the renal pelvis with renal calculus, which has rarely been previously reported. PMID:27123287

  18. Emerging Entities in Renal Neoplasia.

    PubMed

    Mehra, Rohit; Smith, Steven C; Divatia, Mukul; Amin, Mahul B

    2015-12-01

    This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell-papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease-related RCC, succinate dehydrogenase-deficient RCC, and hereditary leiomyomatosis-RCC syndrome-associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors. Emphasis is placed on common gross and morphologic features, differential diagnoses, use of ancillary studies for making accurate diagnoses, molecular alterations, and predicted biologic behavior based on previous studies. PMID:26612218

  19. Isolation of renal brush borders.

    PubMed

    Morré, D James; Hammond, Timothy

    2007-03-01

    Methods are described to isolate intact brush borders and brush border membranes from renal cell homogenates. A rapid method yields sealed vesicles that reconstitute renal brush border transport. In one variation of this protocol, 10 to 20 mM CaCl2 or MgCl2 is added to aggregate non-brush border structures for subsequent removal by centrifugation. For analytical studies, guidance is provided for subsequent purification steps including preparative free-flow and aqueous two-phase partition. Marker enzymes and morphological parameters are included for assessment of yield and fraction purity. PMID:18228514

  20. Mass spectrometry and renal calculi

    PubMed Central

    Purcarea, VL; Sisu, I; Sisu, E

    2010-01-01

    The present review represents a concise and complete survey of the literature covering 2004–2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI–TOF, QTOF, MS–MS) as well as hyphenated methods (GC–MS, LC–MS, CE–MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented. PMID:20968197

  1. Imaging patients with renal impairment.

    PubMed

    Mathur, Mahan; Weinreb, Jeffrey C

    2016-06-01

    Imaging with intravascular contrast media is generally considered safe, particularly in patients without renal failure. However, as renal function deteriorates, the potential risk of nonallergic-type adverse events increases. This presents a unique challenge, particularly when the use of intravenous contrast media is deemed essential for diagnostic purposes. Following a discussion regarding the definition and epidemiology of kidney injury, this review focuses on the evolving understanding of both contrast-induced nephropathy and nephrogenic systemic fibrosis and discusses preventative strategies aimed at minimizing the risk of developing these entities. Alternative non-contrast imaging techniques are also discussed. PMID:27015867

  2. Acute Renal Failure after Uterine Artery Embolization

    SciTech Connect

    Rastogi, Sachin; Wu, Yu-Hsin; Shlansky-Goldberg, Richard D.; Stavropoulos, S. William

    2004-09-15

    Renal failure is a potential complication of any endovascular procedure using iodinated contrast, including uterine artery embolization (UAE). In this report we present a case of acute renal failure (ARF) following UAE performed as a treatment for uterine fibroids. The likely causes of ARF in this patient are explored and the possible etiologies of renal failure in patients undergoing UAE are reviewed.

  3. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    PubMed Central

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  4. Nek8 couples renal ciliopathies to DNA damage and checkpoint control.

    PubMed

    Jackson, Peter K

    2013-08-22

    In this issue, Choi et al. (2013) discover a molecular link between the Nek8 kinase, mutated in the renal ciliopathy nephronophthisis, and DNA damage control by cyclin A/Cdk2 and ATR-Chk1, providing new ideas for targeted therapies limiting tissue degeneration. PMID:23973371

  5. Evidence for Kidney Rejection after Combined Bone Marrow and Renal Transplantation Despite Ongoing Whole-blood Chimerism in Rhesus Macaques

    PubMed Central

    Ramakrishnan, Swetha K; Page, Andrew; Farris, Alton B.; Singh, Karnail; Leopardi, Frank; Hamby, Kelly; Sen, Sharon; Polnett, Aneesah; Deane, Taylor; Song, Mingqing; Stempora, Linda; Strobert, Elizabeth; Kirk, Allan D.; Larsen, Christian P.; Kean, Leslie S.

    2012-01-01

    Although there is evidence linking hematopoietic chimerism-induction and solid organ transplant tolerance, the mechanistic requirements for chimerism-induced tolerance are not clearly elucidated. To address this, we used an MHC-defined primate model to determine the impact of impermanent, T cell-poor, mixed-chimerism on renal allograft survival. We compared two cohorts: one receiving a bone marrow + renal transplant (“BMT/renal”) and one receiving only a renal transplant. Both cohorts received maintenance immunosuppression with CD28/CD40-directed costimulation blockade and sirolimus. As previously demonstrated, this transplant strategy consistently induced compartmentalized donor chimerism, (significant whole-blood chimerism, lacking T cell chimerism). This chimerism was not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival time (MST, 76 days) was not significantly different than the renal transplant alone MST (85 days, p= 0. 46), with histopathology documenting T-cell mediated rejection. Flow cytometric analysis revealed significant enrichment for CD28-/CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between CD28-negative Tem and costimulation blockade-resistant rejection. These results suggest that in some settings, transient T cell-poor chimerism is not sufficient to induce tolerance to a concurrently placed renal allograft and that the presence of this chimerism per se is not an independent biomarker to identify tolerance. PMID:22642491

  6. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use. PMID:25343829

  7. Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function.

    PubMed

    Dhayat, Nasser A; Ackermann, Daniel; Pruijm, Menno; Ponte, Belen; Ehret, Georg; Guessous, Idris; Leichtle, Alexander Benedikt; Paccaud, Fred; Mohaupt, Markus; Fiedler, Georg-Martin; Devuyst, Olivier; Pechère-Bertschi, Antoinette; Burnier, Michel; Martin, Pierre-Yves; Bochud, Murielle; Vogt, Bruno; Fuster, Daniel G

    2016-09-01

    Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population-based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion. PMID:27370409

  8. Dynamics of Urinary Calprotectin after Renal Ischaemia

    PubMed Central

    Ebbing, Jan; Seibert, Felix S.; Pagonas, Nikolaos; Bauer, Frederic; Miller, Kurt; Kempkensteffen, Carsten; Günzel, Karsten; Bachmann, Alexander; Seifert, Hans H.; Rentsch, Cyrill A.; Ardelt, Peter; Wetterauer, Christian; Amico, Patrizia; Babel, Nina; Westhoff, Timm H.

    2016-01-01

    Background: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase—associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. Methods: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5–20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase—associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. Results: Urinary concentrations of calprotectin and neutrophil gelatinase—associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase—associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase—associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia

  9. Chemical Renal Denervation in the Rat

    SciTech Connect

    Consigny, Paul M. Davalian, Dariush; Donn, Rosy Hu, Jie; Rieser, Matthew Stolarik, DeAnne

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  10. Renal function in diabetic nephropathy.

    PubMed

    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  11. [Great moments in renal transplantation].

    PubMed

    Ghossain, Antoine

    2015-01-01

    A selective review of some great moments in renal transplantation experienced or witnessed with some of the great architects of this epic. The path was strewn with hazards, sometimes halts or changes of attitude that harmed or helped some patients. PMID:26591188

  12. Emphysema in the renal allograft

    SciTech Connect

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.

    1985-04-01

    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  13. Renal leiomyosarcoma in a cat.

    PubMed

    Evans, Dawn; Fowlkes, Natalie

    2016-05-01

    Renal leiomyosarcoma was diagnosed in a 10-year-old Domestic Shorthair cat with a 3-year history of clinically managed, chronic renal disease. Sudden death was preceded by a brief episode of mental dullness and confusion. At postmortem examination, the gross appearance of the left kidney was suggestive of hydronephrosis, and a nephrolith was present in the contralateral kidney. However, histology revealed an infiltrative, poorly differentiated, spindle cell sarcoma bordering the grossly cavitated area. Neoplastic cells were immunoreactive for vimentin and smooth muscle actin, which led to a diagnosis of renal leiomyosarcoma; neoplastic cells were not immunoreactive for desmin. Leiomyosarcoma arising in the kidney is a rare occurrence in humans and an even rarer occurrence in veterinary medicine with no prior cases being reported in cats in the English literature. The macroscopic appearance of the tumor at postmortem examination was misleadingly suggestive of hydronephrosis as a result of the large cavitation and may be similar to particularly unusual cases of renal leiomyosarcomas in humans that have a cystic or cavitated appearance. PMID:26975352

  14. Renal effects of percutaneous stone removal

    SciTech Connect

    Eshghi, M.; Schiff, R.G.; Smith, A.D.

    1989-02-01

    Preoperative and postoperative renography with 99mTechnetium-diethylene-triamine pentaacetic acid was performed on 33 patients who were free of renal scarring, infection, and obstruction and who underwent percutaneous renal stone removal. Although there was a transient decrease in renal function postoperatively in some patients, statistically significant reductions in renal function occurred only in 1 patient with an arteriovenous malformation that was embolized and in 1 patient who had a postoperative ureteropelvic junction stricture. The creation of more than one nephrostomy tract did not affect the results. In the absence of serious complications, percutaneous nephrostomy does not have a significant effect on renal function.

  15. [Renal failure and cystic kidney diseases].

    PubMed

    Correas, J-M; Joly, D; Chauveau, D; Richard, S; Hélénon, O

    2011-04-01

    Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease). PMID:21549887

  16. Propranolol disposition in renal failure.

    PubMed Central

    Wood, A J; Vestal, R E; Spannuth, C L; Stone, W J; Wilkinson, G R; Shand, D G

    1980-01-01

    1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine clearance 14.5 +/- 2.8 ml/min) but not on haemodialysis and patients on haemodialysis (creatinine clearance less than 5 ml/min). 3 The effect of haemodialysis on propranolol binding and free fraction was also examined. The percentage of propranolol unbound rose from 7.1% to 9.9%. (P less than 0.001) 20 min following heparinization and beginning haemodialysis. This was accompanied by a large rise in free fatty acids from 0.567 +/- 0.059 to 3.326 +/- 0.691 mumol/ml (P less than 0.005). 4 The blood to plasma concentration ratios of propranolol were significantly higher in patients with renal failure (P less than 0.02) and on haemodialysis (P less than 0.001) and were significantly negatively correlated (P less than 0.001) with the haematocrit. 5 Although the half-life propranolol was significantly shortened in the patients with renal failure (P less than 0.02), there was no change in the apparent liver blood flow, extraction ratio or the principal determinants of steady-state drug concentrations in blood namely oral and intravenous clearance from blood. 6 There is, therefore, no pharmacokinetic basis to adjust the dosage of propranolol in patients with renal failure. PMID:7470370

  17. Renal lesions of nondomestic felids.

    PubMed

    Newkirk, K M; Newman, S J; White, L A; Rohrbach, B W; Ramsay, E C

    2011-05-01

    To comprehensively evaluate the occurrence of renal lesions in a variety of nondomestic felids, necropsy cases from 1978 to 2008 were reviewed from a municipal zoo and a large cat sanctuary for those in which the kidneys were examined histologically. Seventy exotic felids were identified (25 tigers, 18 lions, 6 cougars, 5 leopards, 3 snow leopards, 3 clouded leopards, 3 Canadian lynx, 2 ocelots, 2 bobcats, 2 cheetahs, 1 jaguar), and their histologic renal lesions were evaluated and compared. The most common lesion was tubulointerstitial nephritis (TIN); 36 of 70 (51%) cats were affected to some degree. Lymphocytic interstitial nephritis was the most common lesion in the tigers (9 of 25, 36%) and was rarely seen in other species. Although the renal pelvis was not available for all cats, 28 of 47 (60%) had some degree of lymphocytic pyelitis. There was no significant association between the presence of pyelitis and that of TIN. Only 1 cat had pyelonephritis. Renal papillary necrosis was present in 13 of 70 (19%) cats and was significantly associated with historical nonsteroidal anti-inflammatory drug treatment (odds ratio, 7.1; 95% confidence interval, 1.9 to 26.8). Only 1 cat (lion) had amyloid accumulation, and it was restricted to the corticomedullary junction. Primary glomerular lesions were absent in all cats. Intraepithelial pigment was identified in many of the cats but was not correlated with severity of TIN. Despite several previous reports describing primary glomerular disease or renal amyloidosis in exotic felids, these lesions were rare to absent in this population. PMID:20876911

  18. Renal interventions during endovascular aneurysm repair.

    PubMed

    Davies, Mark G

    2013-12-01

    Renal insufficiency is a risk factor for mortality and morbidity during endovascular aneurysm repair. Multiple changes in practice have occurred to mitigate renal injury and renal dysfunction. Transrenal fixation does carry an increased risk of a decline in renal function in the medium term. Renal stenting for athero-occlusive disease during endovascular aneurysm repair needs careful consideration, as indications have changed and there are unexpected consequences with early vessel occlusion. The growing number of renal interventions during complex endovascular aneurysm repair with the advent of chimney snorkel/periscope techniques and the introduction of fenestrated grafts has shown the resilience of the intervention with relatively low renal issues (approximately 10%), but has also illustrated the need for additional device development. PMID:25220325

  19. Imaging of haemodialysis: renal and extrarenal findings.

    PubMed

    Degrassi, Ferruccio; Quaia, Emilio; Martingano, Paola; Cavallaro, Marco; Cova, Maria Assunta

    2015-06-01

    Electrolyte alterations and extra-renal disorders are quite frequent in patients undergoing haemodialysis or peritoneal dialysis. The native kidneys may be the site of important pathologies in patients undergoing dialysis, especially in the form of acquired renal cystic disease with frequent malignant transformation. Renal neoplasms represents an important complication of haemodialysis-associated acquired cystic kidney disease and imaging surveillance is suggested. Extra-renal complications include renal osteodistrophy, brown tumours, and thoracic and cardiovascular complications. Other important fields in which imaging techniques may provide important informations are arteriovenous fistula and graft complications. Teaching points • Renal neoplasms represent a dreaded complication of haemodialysis.• In renal osteodystrophy bone resorption typically manifests along the middle phalanges.• Brown tumours are well-defined lytic lesions radiographically, possibly causing bone expansion.• Vascular calcifications are very common in patients undergoing haemodialysis.• Principal complications of the AV fistula consist of thrombosis, aneurysms and pseudoaneurysms. PMID:25680325

  20. A Population- and Hospital-based Cross-sectional Study of Renal Function in Hidradenitis Suppurativa.

    PubMed

    Miller, Iben M; Carlson, Nicholas; Mogensen, Ulla B; Ellervik, Christina; Jemec, Gregor B E

    2016-01-01

    The chronic inflammatory skin diseases hidradenitis suppurativa (HS) and psoriasis have been linked to cardiovascular risk factors and the latter has also been linked to possible renal dysfunction. Since basement membrane thinning in the skin of HS patients has been described, we speculated whether similar basement membrane defects might occur in renal tissue. Our objective was to investigate a possible association between HS and renal dysfunction. We performed a hospital and population-based cross-sectional study using estimated Glomerular-Filtration-Rate (eGFR) to assess renal function. Thirty-two hospital individuals with HS, 430 population individuals with HS, and 20,780 population individuals without HS were (controls) identified. The age-, sex-, smoking-, BMI-, hypertension- and diabetes-adjusted analysis revealed a statistically significant higher eGFR for the hospital group with HS and a mean difference in eGFR of 6.81 (1.27-12.35) ml/min/1.73 m2 between the hospital group with HS and the population group without HS. The observed higher eGFR in the hospital group with HS indicates a possible association of HS and renal dysfunction. PMID:25710874

  1. Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic

    SciTech Connect

    Pysher, Michele D.; Sollome, James J.; Regan, Suzanne; Cardinal, Trevor R.; Hoying, James B.; Brooks, Heddwen L.; Vaillancourt, Richard R.

    2007-10-01

    Epidemiological studies link arsenic exposure to increased risks of cancers of the skin, kidney, lung, bladder and liver. Additionally, a variety of non-cancerous conditions such as diabetes mellitus, hypertension, and cardiovascular disease have been associated with chronic ingestion of low levels of arsenic. However, the biological and molecular mechanisms by which arsenic exerts its effects remain elusive. Here we report increased renal hexokinase II (HKII) expression in response to arsenic exposure both in vivo and in vitro. In our model, HKII was up-regulated in the renal glomeruli of mice exposed to low levels of arsenic (10 ppb or 50 ppb) via their drinking water for up to 21 days. Additionally, a similar effect was observed in cultured renal mesangial cells exposed to arsenic. This correlation between our in vivo and in vitro data provides further evidence for a direct link between altered renal HKII expression and arsenic exposure. Thus, our data suggest that alterations in renal HKII expression may be involved in arsenic-induced pathological conditions involving the kidney. More importantly, these results were obtained using environmentally relevant arsenic concentrations.

  2. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis‑induced acute renal injury.

    PubMed

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-08-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway. PMID:27279569

  3. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis-induced acute renal injury

    PubMed Central

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-01-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti-inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured with enzyme-linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen-activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor-κB signal pathway. PMID:27279569

  4. Renal relevant radiology: renal functional magnetic resonance imaging.

    PubMed

    Ebrahimi, Behzad; Textor, Stephen C; Lerman, Lilach O

    2014-02-01

    Because of its noninvasive nature and provision of quantitative measures of a wide variety of physiologic parameters, functional magnetic resonance imaging (MRI) shows great potential for research and clinical applications. Over the past decade, application of functional MRI extended beyond detection of cerebral activity, and techniques for abdominal functional MRI evolved. Assessment of renal perfusion, glomerular filtration, interstitial diffusion, and parenchymal oxygenation turned this modality into an essential research and potentially diagnostic tool. Variations in many renal physiologic markers can be detected using functional MRI before morphologic changes become evident in anatomic magnetic resonance images. Moreover, the framework of functional MRI opened a window of opportunity to develop novel pathophysiologic markers. This article reviews applications of some well validated functional MRI techniques, including perfusion, diffusion-weighted imaging, and blood oxygen level-dependent MRI, as well as some emerging new techniques such as magnetic resonance elastography, which might evolve into clinically useful tools. PMID:24370767

  5. Diagnostic value of routine bone scintigraphy renal imaging in renal cell carcinoma

    SciTech Connect

    Chancellor, M.B.; Konnak, J.W.; Grossman, H.B.

    1989-05-01

    Technetium-99m-phosphate compounds used in bone scanning are excreted by the kidney, and excellent renal images can be obtained on routine bone scintigrams. The preoperative bone scans of 49 patients who underwent radical nephrectomy for renal cell carcinoma between 1981 and 1985 were reviewed for renal imaging. Ninety-four percent of the patients had abnormal bone scan renal images (82% had focal decreased uptake, and 12% had focal increased uptake). Six percent of the renal images were symmetrical bilaterally. When bone scans are employed in the postoperative follow-up of patients with renal cancer, they can be used to assess the status of the remaining kidney.

  6. Renal Cell Carcinoma Arising From Renal Allograft Detected by 18F-FDG PET-CT.

    PubMed

    Guo, Yuehong; Wang, Tie

    2016-05-01

    Renal cell carcinoma arising from renal allograft is a rare condition. A 56-year-old man with a history of 3 renal transplantation due to renal failure presented poor appetite and weight loss for 3 months. Possibility of tumor of unknown origin was suspected. For this reason, an FDG PET/CT was performed, and the images showed a hypermetabolic focus in the lower pole of the left renal transplant, suggestive of a malignant lesion. Subsequent pathological examination following allograft nephrectomy confirmed grade 4 renal cell carcinoma. PMID:26825198

  7. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    SciTech Connect

    Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A.; Veelken, Roland Schmieder, Roland E.; Uder, Michael; Ott, Christian

    2013-08-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP {>=} 140/90 mmHg and 24-h ambulatory BP monitoring ({>=}130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV -15 {+-} 23 vs. MV -16 {+-} 20 mmHg; diastolic: OV -10 {+-} 12 vs. MV -8 {+-} 11 mmHg, both p = NS) as well as 6 months (systolic: OV -18 {+-} 18 vs. MV -17 {+-} 22 mmHg; diastolic: OV -10 {+-} 10 vs. -10 {+-} 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery-namely, the dominant one-is sufficient to induce BP reduction in treatment-resistant hypertension.

  8. Renal outcome of children with unilateral renal agenesis.

    PubMed

    Doğan, Çağla Serpil; Torun Bayram, Meral

    2013-01-01

    The aim of this study was to evaluate associated urological anomalies and renal outcome in children with unilateral renal agenesis (URA). Medical records of 51 cases of URA followed at Şanlıurfa Children 's Hospital between January 2009 and December 2012 were reviewed retrospectively. In all patients, diagnosis was made by abdominal ultrasound (US) and confirmed by a radionuclide scan. The children were between 3 months and 17 years of age (median age: 5 years). There were 31 males (60.8%) and 20 females (39.2%). In 33 patients (67.3%), the left kidney was absent. Urological anomalies were found in 12/51 patients (23.5%), including ureterovesical junction obstruction in 4 (7.8%), bladder dysfunction in 2 (3.9%), and vesicoureteral reflux (VUR), ureteropelvic junction obstruction, ureterovesical and ureteropelvic junction obstruction, duplicated collecting system plus grade IV VUR, ectopic kidney plus grade V VUR, and ectopic kidney in 1 patient (2%) each. Chronic renal insufficiency (CRI) developed in 5/51 patients (9.8%) (stage III in 3 patients and stage IV in 2), 4 of whom had additional urological anomaly; in the remaining 1 patient, a 17-year-old female, imaging studies were normal except for a small and hyperechogenic solitary kidney determined on US. A total of 3 patients (5.8%) developed hypertension, and all except one had an associated urological anomaly. Proteinuria was seen in 2 patients (3.8%) with stage IV CRI, one of whom was also hypertensive. In conclusion, urological anomalies usually accompany URA and should be followed closely to decrease the risk of renal failure. PMID:24577979

  9. A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.

    PubMed

    Yang, Shao-Yu; Lin, Shuei-Liong; Chen, Yung-Ming; Wu, Vin-Cent; Yang, Wei-Shiung; Wu, Kwan-Dun

    2016-01-01

    Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Here, we demonstrated that Sirt1 was mainly expressed in the tubulointerstitial cells of normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. Renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney after a 24-h fast, but no significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation. After consuming a low-salt (0.075%) or 60% calorie restriction diet for 7 days, Sirt1 expression in the rat kidney was significantly increased, whereas a high-salt (8%) diet did not change the level of Sirt1 expression. The low-salt diet also increased Sirt1 expression in the heart, muscle, brain, and fat tissues. The increased Sirt1 that was observed in rats on a low-salt diet was associated with increased ghrelin expression in the distal nephron, with both molecules exhibiting similar distribution patterns. An in vitro experiment suggested that ghrelin increases Sirt1 expression in cortical collecting duct cells by activating ghrelin receptors. Our study indicates that this 'ghrelin-Sirt1 system' may participate in regulating sodium reabsorption in the distal nephron. PMID:27600292

  10. A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats

    PubMed Central

    Yang, Shao-Yu; Lin, Shuei-Liong; Chen, Yung-Ming; Wu, Vin-Cent; Yang, Wei-Shiung; Wu, Kwan-Dun

    2016-01-01

    Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Here, we demonstrated that Sirt1 was mainly expressed in the tubulointerstitial cells of normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. Renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney after a 24-h fast, but no significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation. After consuming a low-salt (0.075%) or 60% calorie restriction diet for 7 days, Sirt1 expression in the rat kidney was significantly increased, whereas a high-salt (8%) diet did not change the level of Sirt1 expression. The low-salt diet also increased Sirt1 expression in the heart, muscle, brain, and fat tissues. The increased Sirt1 that was observed in rats on a low-salt diet was associated with increased ghrelin expression in the distal nephron, with both molecules exhibiting similar distribution patterns. An in vitro experiment suggested that ghrelin increases Sirt1 expression in cortical collecting duct cells by activating ghrelin receptors. Our study indicates that this ‘ghrelin-Sirt1 system’ may participate in regulating sodium reabsorption in the distal nephron. PMID:27600292

  11. Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter Obstruction

    PubMed Central

    Teng, Jing-Fei; Wang, Kai; Li, Yao; Qu, Fa-Jun; Yuan, Qing; Cui, Xin-Gang; Wang, Quan-Xing; Xu, Dan-Feng

    2015-01-01

    Background: Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed its roles in various disease, however, whether SHP-2 involves in renal fibrosis remains unclear. The aim of this study was to explore the roles of myeloid cells SHP-2 in renal interstitial fibrosis. Methods: Myeloid cells SHP-2 gene was conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The total collagen deposition in the renal interstitium was assessed using picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage infiltration in renal tubular interstitium. Quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to analyze the production of cytokines in the kidney. Transferase-mediated dUTP nick-end labeling stain was used to assess the apoptotic renal tubular epithelial cells. Results: Src homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO in myeloid cells significantly reduced collagen deposition in the renal interstitium after UUO. Macrophage infiltration was evidently decreased in renal tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro-inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However, no significant difference was observed in the number of apoptotic renal tubular epithelial cells between wild-type and SHP-2 CKO mice. Conclusions: Our observations suggested that SHP-2 in myeloid cells plays a pivotal role in the pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells may protect renal from inflammatory damage and prevent renal fibrosis after renal injury. PMID:25947403

  12. Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches.

    PubMed

    Reisin, Efrain; Jack, Avanelle V

    2009-05-01

    The increasing prevalence of obesity in the industrialized world is causing an alarming epidemic. Almost 70% of American adults are overweight or obese. The link between increasing body weight and hypertension is well established. Obesity hypertension through metabolic, endocrinic, and systemic hemodynamic alteration causes structural vascular and cardiac adaptations that trigger concentric, eccentric left ventricular hypertrophy and electrophysiological changes, which may increase the risk for congestive heart failure and sudden cardiac death as a result of arrhythmias. The increased renal blood flow in conjunction with a decreased renal vascular resistance causes renal hyperperfusion and hyperfiltration. Such changes lead to glomerulomegaly, focal segmental glomerulosclerosis, tubulointerstitial inflammation, and fibrosis that characterize the renal damage in obese hypertensive subjects. We propose that weight reduction, with the addition of other nonpharmacological approaches that included exercise and reduction in alcohol intake, should be the first choice to treat obesity hypertension. Salt restriction may be helpful only in salt-sensitive patients. The benefits of diet in obese patients include improvement of insulin sensitivity, reduction in sympathetic nervous and renin angiotensin system activities, and restoration of leptin sensitivity. As a consequence of these and other metabolic changes, the previously described systemic and renal hemodynamic alterations improved and the cardiovascular and renal morphological changes induced by obesity were lessened. After reviewing the medications available, we believe that owing to the cardiovascular and renal morbidity and mortality that characterized obesity hypertension, the ACEI or ARBs offer the best cardio-renal protection and should be the pharmacologic treatment of choice. If these alone do not control BP adequately, then a low-dose diuretic should be added as a second approach. Although we strongly believe

  13. Characterization of monoclonal antibodies specific to bovine renal vitamin D hydroxylases.

    PubMed

    Bort, R E; Crivello, J F

    1988-11-01

    Monoclonal antibodies (MAbs) have been produced which recognize specific epitopes on bovine renal mitochondrial vitamin D3 1 alpha- and 24-hydroxylases. Renal mitochondria cytochrome P-450s were partially purified to 0.5-2 nmol/mg by Emulgen 911 and cholate solubilization, followed by chromatography on a 2-(4,6-dichloro-O-biphenyloxy)ethylamine HBR affinity column. Reduced carbon monoxide difference spectra determined that this preparation contained 0.5-2 nmol P-450/mg protein. This preparation contained both 1 alpha- and 24-hydroxylase activities, and Eadie-Hofstee plots of product formation as a function of substrate concentrations have maximum velocities of 1.4 and 4 pmol product/30 min.mg protein and Km values of 690 and 1300 nM, respectively. Bovine renal hydroxylases were isolated by immunoprecipitation from this partially purified P-450 preparation with a polyclonal antibody specific for rat liver microsomal cytochrome P-450 RLM5. This polyclonal antibody immunoprecipitated both 1 alpha- and 24-hydroxylase activities as well as renal mitochondrial cytochrome P-450, as determined by reduced CO spectra. Bovine renal mitochondrial components were immunoisolated and used to immunize BALB/c mouse spleen cells in vitro. MAbs then produced were screened for 1) immunoisolation of renal mitochondrial hydroxylase activity from a partially purified preparation, 2) immunohistochemical detection of antigen in renal proximal tubule cells, and 3) immunoquantitation of renal hydroxylases in a solid phase sandwich (enzyme-linked immunosorbent assay) and by 4) Western blot analysis. MAbs were isolated with specifically immunoprecipitated 1 alpha-hydroxylase activity, 24-hydroxylase activity, or both. In 10 micron sections of bovine kidney, antibodies detected antigen only in proximal tubule cells on the basal surface, which is rich in mitochondria. No antigen was detected in sections of pancreas or liver. In the solid phase sandwich enzyme-linked immunosorbent assay, MAbs

  14. Focus on renal congestion in heart failure

    PubMed Central

    Afsar, Baris; Ortiz, Alberto; Covic, Adrian; Solak, Yalcin; Goldsmith, David; Kanbay, Mehmet

    2016-01-01

    Hospitalizations due to heart failure are increasing steadily despite advances in medicine. Patients hospitalized for worsening heart failure have high mortality in hospital and within the months following discharge. Kidney dysfunction is associated with adverse outcomes in heart failure patients. Recent evidence suggests that both deterioration in kidney function and renal congestion are important prognostic factors in heart failure. Kidney congestion in heart failure results from low cardiac output (forward failure), tubuloglomerular feedback, increased intra-abdominal pressure or increased venous pressure. Regardless of the cause, renal congestion is associated with increased morbidity and mortality in heart failure. The impact on outcomes of renal decongestion strategies that do not compromise renal function should be explored in heart failure. These studies require novel diagnostic markers that identify early renal damage and renal congestion and allow monitoring of treatment responses in order to avoid severe worsening of renal function. In addition, there is an unmet need regarding evidence-based therapeutic management of renal congestion and worsening renal function. In the present review, we summarize the mechanisms, diagnosis, outcomes, prognostic markers and treatment options of renal congestion in heart failure. PMID:26798459

  15. Renal Clearance of Mineral Metabolism Biomarkers.

    PubMed

    van Ballegooijen, Adriana J; Rhee, Eugene P; Elmariah, Sammy; de Boer, Ian H; Kestenbaum, Bryan

    2016-02-01

    CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD. PMID:26047790

  16. Early enhancement of fluid transport in rabbit proximal straight tubules after loss of contralateral renal excretory function.

    PubMed Central

    Tabei, K; Levenson, D J; Brenner, B M

    1983-01-01

    To assess the renal functional adaptation to reduced excretory capacity, we studied whole kidney and single nephron function in anesthetized volume-replete rabbits after unilateral (left kidney) nephrectomy (UNX), ureteral obstruction (UO), or ureteroperitoneostomy (UP). At 24 h, despite the absence of measurable hypertrophy of the contralateral (right) kidney, these procedures significantly increased p-aminohippurate clearance (45-54%) and inulin clearance (CIN) (64-110%) compared with sham-operated control animals. In each group, whole kidney sodium reabsorption increased in proportion to the rise in CIN. To determine whether the intrinsic transport capacity of proximal tubule segments is altered by these maneuvers, we measured fluid volume reabsorption rate (Jv) in isolated superficial proximal straight tubule (PST) segments perfused in vitro, comparing each control tubule (obtained by biopsy of the left kidney immediately before an experimental maneuver) with a corresponding tubule segment obtained 24 h or 7 d later from the contralateral kidney. Control tubule Jv in sham-24 h animals averaged 0.48 +/- 0.04 nl/(min X mm). Jv did not change significantly at 24 h or 7 d after sham maneuvers but increased significantly at 24 h after UNX [delta Jv = 0.13 +/- 0.03 nl/(min X mm)], UO [delta Jv = 0.10 +/- 0.04 nl/(min X mm)], and UP [delta Jv = 0.13 +/- 0.04 nl/(min X mm)]. Jv remained increased by similar amounts at 7 d after UNX and UO. To evaluate whether an increase in glomerular filtration rate (GFR) might be the stimulus to this augmentation in Jv values, methylprednisolone (MP) (15 mg/kg per d) was administered daily to sham-operated animals, a maneuver which induced a 73% rise in CIN by day 5. This procedure also produced a significant increase in Jv in PST at 5 d [delta Jv = 0.16 +/- 0.05 nl/(min X mm)]. The increase in Jv evident in each group at 5 or 7 d was paralleled by an equivalent change in tubule cell volume and apparent tubule luminal surface area in

  17. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update.

    PubMed

    Wan, Cheng; Su, Hua; Zhang, Chun

    2016-01-01

    Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies. PMID:27597884

  18. Design of a multimedia PC-based telemedicine network for the monitoring of renal dialysis patients

    NASA Astrophysics Data System (ADS)

    Tohme, Walid G.; Winchester, James F.; Dai, Hailei L.; Khanafer, Nassib; Meissner, Marion C.; Collmann, Jeff R.; Schulman, Kevin A.; Johnson, Ayah E.; Freedman, Matthew T.; Mun, Seong K.

    1997-05-01

    This paper investigates the design and implementation of a multimedia telemedicine application being undertaken by the Imaging Science and Information Systems Center of the Department of Radiology and the Division of Nephrology of the Department of Medicine at the Georgetown University Medical Center (GUMC). The Renal Dialysis Patient Monitoring network links GUMC, a remote outpatient dialysis clinic, and a nephrologist's home. The primary functions of the network are to provide telemedicine services to renal dialysis patients, to create, manage, transfer and use electronic health data, and to provide decision support and information services for physicians, nurses and health care workers. The technical parameters for designing and implementing such a network are discussed.

  19. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update

    PubMed Central

    Su, Hua

    2016-01-01

    Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies. PMID:27597884

  20. Leiomyosarcoma of the renal vein.

    PubMed

    Imao, Tetsuya; Amano, Toshiyasu; Takemae, Katsurou

    2011-02-01

    A 43-year-old woman was referred to our clinic for evaluation of a left retroperitoneal mass. She presented to our internal medicine department complaining of back pain. Computed tomography (CT) scan revealed a left retroperitoneal mass 55 mm in size in the hilum of the left kidney. Enhanced CT scan and magnetic resonance imaging (MRI) disclosed a poorly staining mass. Metaiodobenzylguanidine scintigraphy demonstrated no accumulation in the mass; moreover, endocrinologic examination was normal. Laparoscopic resection of the left retroperitoneal tumor was attempted; however, strong adhesion between the tumor and the left renal vein was encountered. Thus, left nephrectomy after open conversion was performed. Histological findings indicated leiomyosarcoma originating from the left renal vein. The postoperative course has been uneventful; neither recurrence nor metastasis is evident 2 years postsurgery. PMID:20694494

  1. Mesalazine-induced renal calculi

    PubMed Central

    Jacobsson, Henrik; Eriksen, Jaran; Karlén, Per

    2013-01-01

    Patient: Female, 32 Final Diagnosis: Renal colic Symptoms: Acute colic pain • macrohematuria Medication: Mesalazine Clinical Procedure: CT scan of urinary tract • cystoscopy • gynecological consultation • stone analysis Specialty: Gastroenterology and Hepatology • Clinical Pharmacology Objective: Unexpected drug reaction Background: Mesalazine, a 5-aminosalicylic acid compound, is one of the cornerstones in modern treatment regimens of ulcerative colitis. It is generally well tolerated, although adverse reactions such as nephrotoxicity, perimyocarditis, and pancreatitis have been reported. Case Report: We report the case of a 32-year-old woman with colitis who developed recurrent episodes of renal colic after introduction of mesalazine to her treatment. Biochemical analysis of the stones showed that they were composed of crystalized drug material. Conclusions: To our knowledge this is the first report of mesalazine precipitation in the urinary tract. We believe that it is vital for physicians to recognize this potentially severe adverse effect in the use of this treatment. PMID:24478817

  2. Radiocontrast-induced renal failure

    SciTech Connect

    Misson, R.T.; Cutler, R.E.

    1985-05-01

    Review of the literature concerning contrast-induced renal dysfunction shows that the currently used agents are remarkably safe with careful patient selection. Clinically apparent kidney failure after their use is essentially nonexistent in those without preexistent renal insufficiency. The incidence rises rapidly in those with azotemia from any cause, however, and diabetic persons with nephropathy are perhaps at special risk. Vigorous volume expansion is possibly effective as a preventive measure and may attenuate adverse effects in those in whom postcontrast dysfunction occurs. New agents are becoming available. It is not yet known if these will prove safer or cost-effective. They have some experimentally demonstrated and theoretical advantages over the presently used agents. 58 references, 1 figure, 2 tables.

  3. Renal calculi and their management.

    PubMed

    Melick, R A

    1976-03-01

    Any patient presenting with renal colic requires the taking of a detailed history-- with inquiries about diet and drugs, an examination of the urine, intravenous pyelography and measurement of the calcium concentration in serum and urine. Any stone passed should be analysed. Recurrent stone formation warrants more comprehensive metabolic investigation. The cause of renal calculi in most patients is still not known. When a cause is found, specific treatment can prevent or control stone formation. For the majority in whom no abnormality is detected, various methods of reducing stone formation have been tried but results are disappointing. The most important points in management are the early detection and effective treatment of urinary tract infection or obstruction and the maintenance of a high fluid intake. PMID:1272102

  4. Asymptomatic hyperuricemia following renal transplantation

    PubMed Central

    Bellomo, Gianni

    2015-01-01

    Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end. PMID:26167455

  5. Asymptomatic hyperuricemia following renal transplantation.

    PubMed

    Bellomo, Gianni

    2015-07-01

    Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end. PMID:26167455

  6. Leiomyoma in a Renal Allograft.

    PubMed

    Li, Yan Jun; Siriwardana, Amila Rohan; Symons, James Lawrence Penn; O'Neill, Gordon Francis; Qiu, Min Ru; Furlong, Timothy John

    2016-01-01

    Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year. PMID:27195169

  7. Leiomyoma in a Renal Allograft

    PubMed Central

    Li, Yan Jun; Siriwardana, Amila Rohan; Symons, James Lawrence Penn; O'Neill, Gordon Francis; Qiu, Min Ru; Furlong, Timothy John

    2016-01-01

    Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year. PMID:27195169

  8. Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel ROMK2 and regulates its function.

    PubMed

    Renigunta, Aparna; Renigunta, Vijay; Saritas, Turgay; Decher, Niels; Mutig, Kerim; Waldegger, Siegfried

    2011-01-21

    Tamm-Horsfall glycoprotein (THGP) or Uromodulin is a membrane protein exclusively expressed along the thick ascending limb (TAL) and early distal convoluted tubule (DCT) of the nephron. Mutations in the THGP encoding gene result in Familial Juvenile Hyperuricemic Nephropathy (FJHN), Medullary Cystic Kidney Disease type 2 (MCKD-2), and Glomerulocystic Kidney Disease (GCKD). The physicochemical and biological properties of THGP have been studied extensively, but its physiological function in the TAL remains obscure. We performed yeast two-hybrid screening employing a human kidney cDNA library and identified THGP as a potential interaction partner of the renal outer medullary potassium channel (ROMK2), a key player in the process of salt reabsorption along the TAL. Functional analysis by electrophysiological techniques in Xenopus oocytes showed a strong increase in ROMK current amplitudes when co-expressed with THGP. The effect of THGP was specific for ROMK2 and did not influence current amplitudes upon co-expression with Kir2.x, inward rectifier potassium channels related to ROMK. Single channel conductance and open probability of ROMK2 were not altered by co-expression of THGP, which instead increased surface expression of ROMK2 as determined by patch clamp analysis and luminometric surface quantification, respectively. Despite preserved interaction with ROMK2, disease-causing THGP mutants failed to increase its current amplitude and surface expression. THGP(-/-) mice exhibited increased ROMK accumulation in intracellular vesicular compartments when compared with WT animals. Therefore, THGP modulation of ROMK function confers a new role of THGP on renal ion transport and may contribute to salt wasting observed in FJHN/MCKD-2/GCKD patients. PMID:21081491

  9. Immunotherapy in renal cell carcinoma.

    PubMed

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  10. [Immune tolerance after renal transplantation].

    PubMed

    Krajewska, Magdalena; Weyde, Wacław; Klinger, Marian

    2006-01-01

    Progress in immunosuppressive therapy has improved short-term survival of renal allografts by decreasing the frequency of acute rejections. However, the long-term survival of renal grafts has not improved. Transplanted kidneys are lost in the late period after transplantation as a result of vasculopathy and chronic rejection. Immunological tolerance means the lack of immunological activity towards certain antigens while the response towards others remains correct. The induction of immunological tolerance of donor antigens (transplant tolerance) is examined intensively to work out treatment methods which will allow prevention of chronic allograft rejection. The paper includes an overview of current knowledge on allograft tolerance. Immune response to alloantigens is described and the mechanisms of immunological tolerance induction (including clonal deletion, anergy connected with the microchimerism phenomenon, and active suppression caused by regulatory lymphocytes) are characterized. The role of dendritic cells in the process of inducing and maintaining tolerance is highlighted. Tolerance-inducing strategies in renal transplant recipients and clinically applied evaluation methods are presented. At present, optimizing recipient matching is used to decrease the risk of graft rejection. Hopefully, gene therapy will be possible in the near future. However, before introducing such a procedure into clinical studies, optimal therapy conditions and risk evaluation must be defined in tests on animals. PMID:16552396

  11. Renal effects of environmental and occupational lead exposure.

    PubMed Central

    Loghman-Adham, M

    1997-01-01

    Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content. Images p928-a Figure 1. Figure 2. Figure 2. Figure 3. PMID:9300927

  12. Diabetes, Renal and Cardiovascular Disease in p47phox−/− Chronic Granulomatous Disease

    PubMed Central

    Leiding, Jennifer W.; Marciano, Beatriz E.; Zerbe, Christa S.; DeRavin, Suk See; Malech, Harry L.

    2014-01-01

    Chronic granulomatous disease is a rare immunodeficiency due to defects in the phagocyte NADPH oxidase. The X-linked form (gp91phox deficiency) accounts for about 70 % of cases; autosomal recessive p47phox deficiency accounts for about 25 % of cases. We identified a 10 % incidence of diabetes in p47phox deficient CGD, but none in X-linked CGD. Renal and cardiovascular diseases were also higher in p47phox deficiency. p47phox deficient CGD has noninfectious morbidities distinct from those in X-linked CGD. PMID:23386289

  13. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  14. Renal dysplasia in boxers and Finnish harriers.

    PubMed

    Hoppe, A; Karlstam, E

    2000-09-01

    Puppies from two litters of dogs were found to have severe polyuria and polydipsia. Four of the dogs were investigated by means of clinical examination, haematological and biochemical analysis, and urinalysis. A modified water deprivation response test was also performed in two of the dogs. Renal changes on postmortem examination in three of the dogs were found to be consistent with renal dysplasia. A possible explanation for the finding of hyposthenuria and the extreme polyuria and polydipsia in association with renal dysplasia may be lack of response to antidiuretic hormone owing to anomalous maturation of the renal tubules. Six other puppies from the two litters of dogs did not show any clinical signs of polyuria and polydipsia, although postmortem examination in one of them also revealed renal dysplasia. The clinical features of renal dysplasia may therefore vary greatly between individuals. PMID:11023130

  15. Renal Anomalies Associated with Ectopic Neurohypophysis

    PubMed Central

    Özen, Samim; Şişmek, Damla Gökşen; Önder, Asan; Darcan, Şükran

    2011-01-01

    Objective: Although the etiology of ectopic neurohypophysis that leads to pituitary hormone deficiencies is not yet clearly understood, birth trauma or genetic factors have been considered responsible. Concurrent cranial and extracranial congenital anomalies have been reported in such cases. The aim of the present study was to investigate the frequency of renal anomalies in nonsyndromic cases with ectopic neurohypophysis. Methods: We retrospectively evaluated the medical records of 20 patients with ectopic neurohypophysis who were followed up between January 1990 and December 2007 in a tertiary University Hospital. Results: Renal anomalies were identified in three (15%) cases including unilateral renal agenesis in one case, renal hypoplasia in one case, and double collecting system and unilateral renal agenesis in one case. Conclusions: In the present study, the increased frequency of renal anomalies in cases of ectopic neurohypophysis was highlighted, and it was emphasized that there might be common genetic factors that lead to such associations. Conflict of interest:None declared. PMID:21750632

  16. [Relationship of renal cell carcinoma and hypertension].

    PubMed

    Masanauskiene, Edita; Naudziūnas, Albinas; Jankauskiene, Laima; Unikauskas, Alvydas

    2009-01-01

    The morbidity and mortality due to renal cell carcinoma has increased worldwide over the last 30 years. Renal cell carcinoma accounts for about 90-95% of all renal tumors. The mean age of patients with this type of tumor ranges between 50 and 70 years. It is important to note that primary arterial hypertension as well as obesity and smoking are considered as independent risk factors for renal cell carcinoma. The increase in both systolic and diastolic blood pressure as well as the severity of arterial hypertension may have an impact on development of renal cell carcinoma. We describe the case of a 45-year-old male patient with hypertensive crisis. Computed tomography scan revealed renal cell carcinoma, which was confirmed histologically after surgical treatment. PMID:20173406

  17. [Current management of renal artery stenosis].

    PubMed

    Lenz, T

    2013-12-01

    Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (ischemic kidney disease) or rarely pulmonary flush edema may occur. Renal artery stenosis may be treated by revascularization, using either percutaneous (balloon angioplasty, stenting) or less common open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management alone (except for fibromuscular disease). Furthermore, endovascular procedures are associated with substantial risks. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Careful patient selection is essential to maximize the potential benefit. PMID:24217529

  18. Acute renal failure due to falciparum malaria.

    PubMed

    Habte, B

    1990-01-01

    Seventy-two patients with severe falciparum malaria are described. Twenty-four (33.3%) were complicated by acute renal failure. Comparing patients with renal failure and those without, statistically significant differences occurred regarding presence of cerebral malaria (83% vs 46%), jaundice (92% vs 33%), and death (54% vs 17%). A significantly higher number of patients with renal failure were nonimmune visitors to malaria endemic regions. Renal failure was oliguric in 45% of cases. Dialysis was indicated in 38%, 29% died in early renal failure, and 33% recovered spontaneously. It is concluded that falciparum malaria is frequently complicated by cerebral malaria and renal failure. As nonimmune individuals are prone to develop serious complications, malaria prophylaxis and vigorous treatment of cases is mandatory. PMID:2236718

  19. The Role of the Renal Ammonia Transporter Rhcg in Metabolic Responses to Dietary Protein

    PubMed Central

    Bounoure, Lisa; Ruffoni, Davide; Müller, Ralph; Kuhn, Gisela Anna; Devuyst, Olivier

    2014-01-01

    High dietary protein imposes a metabolic acid load requiring excretion and buffering by the kidney. Impaired acid excretion in CKD, with potential metabolic acidosis, may contribute to the progression of CKD. Here, we investigated the renal adaptive response of acid excretory pathways in mice to high-protein diets containing normal or low amounts of acid-producing sulfur amino acids (SAA) and examined how this adaption requires the RhCG ammonia transporter. Diets rich in SAA stimulated expression of enzymes and transporters involved in mediating NH4+ reabsorption in the thick ascending limb of the loop of Henle. The SAA-rich diet increased diuresis paralleled by downregulation of aquaporin-2 (AQP2) water channels. The absence of Rhcg transiently reduced NH4+ excretion, stimulated the ammoniagenic pathway more strongly, and further enhanced diuresis by exacerbating the downregulation of the Na+/K+/2Cl− cotransporter (NKCC2) and AQP2, with less phosphorylation of AQP2 at serine 256. The high protein acid load affected bone turnover, as indicated by higher Ca2+ and deoxypyridinoline excretion, phenomena exaggerated in the absence of Rhcg. In animals receiving a high-protein diet with low SAA content, the kidney excreted alkaline urine, with low levels of NH4+ and no change in bone metabolism. Thus, the acid load associated with high-protein diets causes a concerted response of various nephron segments to excrete acid, mostly in the form of NH4+, that requires Rhcg. Furthermore, bone metabolism is altered by a high-protein acidogenic diet, presumably to buffer the acid load. PMID:24652796

  20. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3

    PubMed Central

    Fenton, Robert A.; Poulsen, Søren B.; de la Mora Chavez, Samantha; Soleimani, Manoocher; Busslinger, Meinrad; Rieg, Timo

    2015-01-01

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation, resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2, and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605, or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na+/bicarbonate cotransporter NBCe1, pretreatment with DIDS inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis. PMID:25925253

  1. Adult nephron-specific MR-deficient mice develop a severe renal PHA-1 phenotype.

    PubMed

    Canonica, Jérémie; Sergi, Chloé; Maillard, Marc; Klusonova, Petra; Odermatt, Alex; Koesters, Robert; Loffing-Cueni, Dominique; Loffing, Johannes; Rossier, Bernard; Frateschi, Simona; Hummler, Edith

    2016-05-01

    Aldosterone is the main mineralocorticoid hormone controlling sodium balance, fluid homeostasis, and blood pressure by regulating sodium reabsorption in the aldosterone-sensitive distal nephron (ASDN). Germline loss-of-function mutations of the mineralocorticoid receptor (MR) in humans and in mice lead to the "renal" form of type 1 pseudohypoaldosteronism (PHA-1), a case of aldosterone resistance characterized by salt wasting, dehydration, failure to thrive, hyperkalemia, and metabolic acidosis. To investigate the importance of MR in adult epithelial cells, we generated nephron-specific MR knockout mice (MR(Pax8/LC1)) using a doxycycline-inducible system. Under standard diet, MR(Pax8/LC1) mice exhibit inability to gain weight and significant weight loss compared to control mice. Interestingly, despite failure to thrive, MR(Pax8/LC1) mice survive but develop a severe PHA-1 phenotype with higher urinary Na(+) levels, decreased plasma Na(+), hyperkalemia, and higher levels of plasma aldosterone. This phenotype further worsens and becomes lethal under a sodium-deficient diet. Na(+)/Cl(-) co-transporter (NCC) protein expression and its phosphorylated form are downregulated in the MR(Pax8/LC1) knockouts, as well as the αENaC protein expression level, whereas the expression of glucocorticoid receptor (GR) is increased. A diet rich in Na(+) and low in K(+) does not restore plasma aldosterone to control levels but is sufficient to restore body weight, plasma, and urinary electrolytes. In conclusion, MR deletion along the nephron fully recapitulates the features of severe human PHA-1. ENaC protein expression is dependent on MR activity. Suppression of NCC under hyperkalemia predominates in a hypovolemic state. PMID:26762397

  2. Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in an in vivo rat model of renal ischemia-reperfusion.

    PubMed

    Mahfoudh-Boussaid, Asma; Hadj Ayed Tka, Kaouther; Zaouali, Mohamed Amine; Roselló-Catafau, Joan; Ben Abdennebi, Hassen

    2014-10-01

    Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1α (HIF-1α) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 μL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 µg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 µg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 μmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1α (333 ± 48 vs. 177 ± 14 µg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1α stabilization and HO-1 activation. PMID:25246344

  3. Linking | Smokefree.gov

    Cancer.gov

    Links to individual pages within the Smokefree.gov Web site are permissible, provided attribution is made to Smokefree.gov and any descriptive notes accurately reflect the content of the linked page(s).

  4. Discovery of Renal Tuberculosis in a Partial Nephrectomy Specimen Done for Renal Tumor

    PubMed Central

    Saadi, Ahmed; Ayed, Haroun; Bouzouita, Abderrazak; Kerkeni, Walid; Cherif, Mohamed; Ben Slama, Riadh M.; Derouiche, Amine; Chebil, Mohamed

    2015-01-01

    The association of renal cancer and renal tuberculosis is uncommon. While the incidental discovery of renal cell carcinoma in a tuberculous kidney is a classical finding, the discovery of tuberculous lesions after nephrectomy for cancer is exceptional. We report the case of a female patient aged 60 who had a partial nephrectomy for a 5 cm exophytic kidney tumor. Pathological examination concluded that renal clear cell carcinoma associated with follicular caseo tuberculosis. PMID:26793504

  5. Renal Infarction Caused by Spontaneous Renal Artery Dissection: Treatment with Catheter-Directed Thrombolysis and Stenting

    SciTech Connect

    Jeon, Yong Sun Cho, Soon Gu; Hong, Ki Cheon

    2009-03-15

    Spontaneous renal artery dissection (SRAD) is rare and presents a diagnostic and therapeutic challenge. We report a case of a 36-year-old man who had an SRAD-complicated renal infarction. The patient experienced severe unilateral flank pain. Enhanced abdominal computed axial tomography scan showed renal infarction, and urinalysis showed no hematuria. Selective renal angiography was essential to evaluate the extent of dissection and suitability for repair. The patient was treated with catheter-directed thrombolysis and frenal artery stenting.

  6. Favourable outcome of scleroderma renal crisis.

    PubMed Central

    Collins, D A; Patel, S; Eastwood, J B; Bourke, B E

    1996-01-01

    Severe hypertension and rapidly progressive acute renal failure is a well recognized complication of scleroderma, often referred to as the renal crisis, and widely thought to cause irreversible deterioration in renal function. With the advent of angiotensin-converting-enzyme inhibitors (ACE-I) the outlook for patients with this condition has dramatically improved. We report here one such patient. Images Figure 1 PMID:8709086

  7. Endovascular Exclusion of Renal Artery Aneurysm

    SciTech Connect

    Andersen, Poul Erik Rohr, Nils

    2005-06-15

    A patient who was operated for an abdominal aortic aneurysm 7 years earlier presented with recently discovered iliac and renal artery aneurysms. The renal artery had an angulation of 90{sup o}, but the aneurysm was successfully excluded using a covered vascular stent graft placed over an extrastiff guidewire. Even in cases of complex anatomy of a renal aneurysm, endovascular treatment should be considered. With development of more flexible and low-profile endoprosthesis with accurate deployment, these have become more usable.

  8. Myocardial Calcinosis in Chronic Renal Failure

    PubMed Central

    Kempf, Ashley E.; Momeni, Maryam Golshan; Saremi, Farhood

    2009-01-01

    The authors are presenting an 18 year old male with history of end stage renal disease and rejected renal transplant. In his workup echocardiogram and non contract CT of chest revealed diffuse endocardial and myocardial calcifications. Extensive cardiac calcification is a rare but important entity in relation to end stage renal disease as it may cause complications such as valvular dysfunction and fatal arrhythmia. PMID:22470643

  9. [Renal colic: new care in emergency centers].

    PubMed

    Morandi, Eléonore; Kherad, Omar; Chollet, Yves; Dussoix, Philippe

    2016-02-01

    The prevalence of renal colic is increasing in industrialized countries, representing a frequent reason for consultation in emergencies. Most patients have simple renal colic that will require analgesia and ambulatory monitoring. Doctors working in emergency centers play a key role in the diagnosis, care and guidance of these patients. They must identify factors of gravity and request urological advice if necessary. This article summarizes the recent diagnostic and therapeutic innovations in the management and guidance of renal colic in emergency centers. PMID:26999995

  10. Renal dysfunction associated with liver transplantation.

    PubMed Central

    Jindal, R. M.; Popescu, I.

    1995-01-01

    It has been known for some time that a variety of liver diseases affect kidney function, but renal dysfunction associated with orthotopic liver transplantation has received scant attention. Although the mechanisms mediating these abnormalities are incompletely defined, advances in the understanding of renal pathophysiology after liver transplantation have made it possible to develop new treatment strategies. Aggressive and early intervention to diagnose and treat renal complications associated with liver transplantation should be the goal for transplant centres. PMID:7479462

  11. Commercial Web Site Links.

    ERIC Educational Resources Information Center

    Thelwall, Mike

    2001-01-01

    Discusses business use of the Web and related search engine design issues as well as research on general and academic links before reporting on a survey of the links published by a collection of business Web sites. Results indicate around 66% of Web sites do carry external links, most of which are targeted at a specific purpose, but about 17%…

  12. Purinergic signaling in inflammatory renal disease

    PubMed Central

    Arulkumaran, Nishkantha; Turner, Clare M.; Sixma, Marije L.; Singer, Mervyn; Unwin, Robert; Tam, Frederick W. K.

    2013-01-01

    Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signaling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signaling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive) role of purinergic signaling. We discuss the role of extracellular nucleotides in adaptation to ischemic renal injury and in the pathogenesis of inflammatory renal disease. PMID:23908631

  13. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  14. Sickle cell disease: renal manifestations and mechanisms

    PubMed Central

    Nath, Karl A.; Hebbel, Robert P.

    2015-01-01

    Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

  15. Abnormal patterns of the renal veins

    PubMed Central

    Azari, Hassan; Abedinzadeh, Mehdi

    2012-01-01

    Knowledge of the renal vascular anatomy may greatly contribute to the success of surgical, invasive and radiological procedures of the retroperitoneal region. Here, morphometric and histological studies of a human cadaveric specimen presented a complex, anomalous pattern of renal veins. The left renal vein had an oblique retro-aortic course and received two lumbar veins. It bifurcated near its drainage point into the inferior vena cava. The right renal vein received the right testicular vein. In addition, the left kidney was located at a low position. The spleen was enlarged. The present case is unique and provides information that may help surgeons or angiologists to apply safer interventions. PMID:22536553

  16. Cognitive and emotional effects of renal transplantation

    PubMed Central

    Pawar, A.A.; Rathod, J.; Chaudhury, S.; Saxena, S.K.; Saldanha, D.; Ryali, V.S.S.R.; Srivastava, K.

    2006-01-01

    Background: Recent studies have shown a high prevalence of depression and cognitive changes in patients with end-stage renal disease (ERSD) and renal transplant recipients. There are few data available on the cognitive and emotional changes in patients undergoing renal transplantation in India. Aim: To evaluate the changes in cognitive profile and depression in renal transplant recipients. Methods: Thirty consecutive patients undergoing renal transplantation were evaluated 1 month before and 3 months after successful renal transplant with Beck Depression Inventory (BDI), Weschler Adult Performance Intelligence Scale (WAPIS), Luria Nebraska Neuropsychological battery (LNNB) and Life satisfaction scale. Results: Our study revealed an 86.7% prevalence of depression in ESRD patients as compared to 56.7% in post renal transplant patients. Analysis of neurocognitive functions on LNNB did not reveal any significant impairment. Furthermore, analysis of the Life satisfaction scale revealed most of the patients scored high satisfaction levels despite the stress of their disease. Results on WAPIS brought out significant improvement in intelligence quotient (IQ) after renal transplantation. Conclusion: Successful renal transplant is associated with improvement in depression, IQ and life satisfaction. PMID:20703410

  17. Early origin of adult renal disease.

    PubMed

    Maringhini, Silvio; Corrado, Ciro; Maringhini, Guido; Cusumano, Rosa; Azzolina, Vitalba; Leone, Francesco

    2010-10-01

    Observational studies in humans and experimental studies in animals have clearly shown that renal failure may start early in life. 'Fetal programming' is regulated by adaptations occurring in uterus including maternal nutrition, placental blood supply, and epigenetic changes. Low birth weight predisposes to hypertension and renal insufficiency. Congenital abnormalities of the kidney and urinary tract, adverse postnatal events, wrong nutritional habits may produce renal damage that will become clinically relevant in adulthood. Prevention should start early in children at risk of renal disease. PMID:20822331

  18. Effects of renal lymphatic occlusion and venous constriction on renal function.

    PubMed Central

    Stolarczyk, J.; Carone, F. A.

    1975-01-01

    The effects of renal lymphatic occlusion or increased lymph flow due to renal vein constriction on renal function were investigated in rats. In each experiment, the renal lymphatics or vein of the left kidney were occluded or constricted and the right kidney served as a control. Occlusion of renal lymphatics caused renal enlargement, no change in glomerular filtration rate, a marked increase in urine flow and solute excretion without any change in urine osmolality, and enhanced urinary loss of urea, potassium, sodium and ammonium. Urea concentrations in medullary and papillary tissues were significantly elevated. Renal vein constriction caused renal enlargement and a marked drop in glomerular filtration rate, urine volume, urine osmolality and solute excretion. tissue concentrations of urea and potassium were decreased in the medulla and papilla and total tissue solute was significantly decreased in the papilla. The data indicate that in the rat, renal lymphatic occlusion traps urea in the medulla and induces a urea diuresis resulting in a large flow of normally concentrated urine. On the other hand, increased lymph flow secondary to renal vein constriction decreases medullary urea and potassium concentrations and papillary osmolality. These changes and the reduced glomerular filtration rate result in a small flow if dilute urine. Thus both renal lymphatic occlusion and enhanced lymph flow have a significant effect on renal function. Images Fig 1 PMID:1122006

  19. Transcatheter Embolization of a Renal Arteriovenous Fistula Complicated by an Aneurysm of the Feeding Renal Artery

    SciTech Connect

    Kensella, Denise; Kakani, Nirmal Pocock, Richard; Thompson, John; Cowan, Andrew; Watkinson, A.

    2008-03-15

    Renal arteriovenous fistula (AVF) is rare. Renal AVF complicated by aneurysm of the feeding artery presents a technical challenge for endovascular treatment. We report a case managed by covered stenting of the renal artery aneurysm, coil embolization of the fistula, and bare stenting of the aorta.

  20. Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure.

    PubMed

    McDonough, Alicia A

    2010-04-01

    One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na(+) and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na(+)/H(+) exchanger isoform 3 (NHE3) and the Na(+)-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na(+) transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS. PMID:20106993

  1. MORPHOMETRIC, BIOCHEMICAL, AND PHYSIOLOGICAL ASSESSMENT OF PERINATALLY INDUCED RENAL DYSFUNCTION

    EPA Science Inventory

    Three chemicals, known either to alter renal development when administered during fetal development or to affect renal function when administered to adult rats, were administered to Sprague-Dawley rats at critical periods of renal development. Chlorambucil (CHL) was administered ...

  2. ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

    PubMed Central

    Jones, Frances E.; Bailey, Matthew A.; Murray, Lydia S.; Lu, Yinhui; McNeilly, Sarah; Schlötzer-Schrehardt, Ursula; Lennon, Rachel; Sado, Yoshikazu; Brownstein, David G.; Mullins, John J.; Kadler, Karl E.; Van Agtmael, Tom

    2016-01-01

    ABSTRACT Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies. PMID:26839400

  3. A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia.

    PubMed

    Adam, Julie; Yang, Ming; Bauerschmidt, Christina; Kitagawa, Mitsuhiro; O'Flaherty, Linda; Maheswaran, Pratheesh; Özkan, Gizem; Sahgal, Natasha; Baban, Dilair; Kato, Keiko; Saito, Kaori; Iino, Keiko; Igarashi, Kaori; Stratford, Michael; Pugh, Christopher; Tennant, Daniel A; Ludwig, Christian; Davies, Benjamin; Ratcliffe, Peter J; El-Bahrawy, Mona; Ashrafian, Houman; Soga, Tomoyoshi; Pollard, Patrick J

    2013-05-30

    The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target. PMID:23643539

  4. Successful technical and clinical outcome using a second generation balloon expandable coronary stent for transplant renal artery stenosis: Our experience.

    PubMed

    Salsamendi, Jason; Pereira, Keith; Baker, Reginald; Bhatia, Shivank S; Narayanan, Govindarajan

    2015-10-01

    Transplant renal artery stenosis (TRAS) is a vascular complication frequently seen because of increase in the number of renal transplantations. Early diagnosis and management is essential to optimize a proper graft function. Currently, the endovascular treatment of TRAS using angioplasty and/or stenting is considered the treatment of choice with the advantage that it does not preclude subsequent surgical correction. Treatment of TRAS with the use of stents, particularly in tortuous transplant renal anatomy presents a unique challenge to an interventional radiologist. In this study, we present three cases from our practice highlighting the use of a balloon-expandable Multi-Link RX Ultra coronary stent system (Abbott Laboratories, Abbott Park, Illinois, USA) for treating high grade focal stenosis along very tortuous renal arterial segments. Cobalt-Chromium alloy stent scaffold provides excellent radial force, whereas the flexible stent design conforms to the vessel course allowing for optimal stent alignment. PMID:26629289

  5. Successful technical and clinical outcome using a second generation balloon expandable coronary stent for transplant renal artery stenosis: Our experience

    PubMed Central

    Salsamendi, Jason; Pereira, Keith; Baker, Reginald; Bhatia, Shivank S; Narayanan, Govindarajan

    2015-01-01

    Transplant renal artery stenosis (TRAS) is a vascular complication frequently seen because of increase in the number of renal transplantations. Early diagnosis and management is essential to optimize a proper graft function. Currently, the endovascular treatment of TRAS using angioplasty and/or stenting is considered the treatment of choice with the advantage that it does not preclude subsequent surgical correction. Treatment of TRAS with the use of stents, particularly in tortuous transplant renal anatomy presents a unique challenge to an interventional radiologist. In this study, we present three cases from our practice highlighting the use of a balloon-expandable Multi-Link RX Ultra coronary stent system (Abbott Laboratories, Abbott Park, Illinois, USA) for treating high grade focal stenosis along very tortuous renal arterial segments. Cobalt–Chromium alloy stent scaffold provides excellent radial force, whereas the flexible stent design conforms to the vessel course allowing for optimal stent alignment. PMID:26629289

  6. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    PubMed Central

    Thottathil, Mujeeburahiman; Verma, Ashish; D’souza, Nischith; Khan, Altaf

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too. PMID:27453671

  7. The Retroperitoneal Laparoscopic Renal Capsulectomy for Spontaneous Renal Subcapsular Fluid Collection

    PubMed Central

    Zhu, Guodong; Wu, Dapeng; Wu, Kaijie; Song, Wenbin; Yang, Zhishang; Zhang, Yue; Zhang, Linlin; He, Dalin

    2016-01-01

    Abstract Spontaneous renal subcapsular fluid collection may occur as a rare presentation of nephritic syndrome, and distension of the renal capsula and Gerota fascia due to massive fluid accumulation may cause pain. In addition, hypertension secondary to renal ischemia and activation of renin–angiotensin–aldosterone system may also occur. The objective of this study is to evaluate the surgical outcome of retroperitoneal laparoscopic renal capsulectomy for patients with this disease. We retrospectively analyzed the clinical data of 10 female patients with spontaneous renal subcapsular fluid collection, diagnosed with B ultrasound and enhanced computed tomography (CT) scan. Eight patients first underwent percutaneous renal subcapsular drainage, which seemed to be less effective, and then all patients underwent retroperitoneal laparoscopic renal capsulectomy. The volume of renal subcapsular fluid was documented, the fluid was examined by routine biochemical tests, and the excised renal capsules underwent pathological examination individually. The postoperative drainage time for each patient was documented, and follow-up was conducted 1, 3, 6, 12 months, and 2 years postoperatively. Retroperitoneal laparoscopic renal capsulectomy was successfully performed in all patients with no major complications. The average volume of renal subcapsular fluid was 436 milliliter (mL, 180–880 mL) in light yellow color, and the concentration of creatinine and urea nitrogen was quite similar to that of serum. The pathological findings revealed fibrous dysplasia of the renal capsule with chronic infiltration of inflammatory cells. The average drainage time was 11.5 days (5–30 days) postoperatively. All patients recovered 1 month after the operation and there were no recurrences with a mean follow-up period of 12 months (6–24 months). The reason for spontaneous renal subcapsular fluid collection is unknown, and the aim of treatment is mainly to alleviate symptoms. In our

  8. Renal opiate receptor mediation of renin secretion to renal nerve stimulation in the dog.

    PubMed

    Koyama, S; Hosomi, H

    1986-06-01

    The present study was designed to evaluate renal opiate receptor mediation of the renin secretion response to electrical stimulation of the renal nerves in the pentobarbital sodium-anesthetized dog by use of the opiate agonist leucine-enkephalin (Leu-enk) and the opiate antagonist naloxone. In all animals studied, left kidneys were pump perfused at a constant renal blood flow. Renal perfusion pressure (RPP) and glomerular filtration rate (GFR) were unaltered at a stimulation frequency of 1.0 Hz; however, renin secretion rate (RSR) increased significantly in the nontreated group. High-frequency renal nerve stimulation (10 Hz) increased RPP and decreased GFR. RSR at the high-frequency stimulation was significantly augmented in the nontreated group. Renal arterial infusion of either Leu-enk (25 micrograms X kg-1 X min-1) or naloxone (7 micrograms X kg-1 X min-1) did not alter base-line levels of renal hemodynamics and RSR and did not produce significant changes in these variables even when renal nerves were stimulated at the low frequency; however, Leu-enk inhibited RPP and RSR responses to the high-frequency stimulation, and naloxone augmented these responses. Phentolamine (13 micrograms X kg-1 X min-1) prevented renal hemodynamic responses to the renal nerve stimulation, whereas RSR responses to the stimulation were unaffected. Propranolol (8 micrograms X kg-1 X min-1) resulted in decreases in RSR at the renal nerve stimulation despite the presence of changes in renal hemodynamics similar to the other groups. The results indicate that intrarenal opiate receptors may participate in inhibiting renal secretion of renin mediated by the renal nerves when renal vasoconstriction and reduction of GFR occurred at the high-frequency stimulation. PMID:3013030

  9. Analysis of Renal Anomalies in VACTERL Association

    PubMed Central

    Cunningham, Bridget K.; Khromykh, Alina; Martinez, Ariel F.; Carney, Tyler; Hadley, Donald W.; Solomon, Benjamin D.

    2014-01-01

    VACTERL association refers to a combination of congenital anomalies that can include: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula with esophageal atresia, Renal anomalies (typically structural renal anomalies), and Limb anomalies. We conducted a description of a case series to characterize renal findings in a cohort of patients with VACTERL association. Out of the overall cohort, 48 patients (with at least 3 component features of VACTERL and who had abdominal ultrasound performed) met criteria for analysis. Four other patients were additionally analyzed separately, with the hypothesis that subtle renal system anomalies may occur in patients who would not otherwise meet criteria for VACTERL association. Thirty-three (69%) of the 48 patients had a clinical manifestation affecting the renal system. The most common renal manifestation (RM) was vesicoureteral reflux (VUR) in addition to a structural defect (present in 27%), followed by unilateral renal agenesis (24%), and then dysplastic/multicystic kidneys or duplicated collected system (18% for each). Twenty-two (88%) of the 25 patients with a structural RM had an associated anorectal malformation. Individuals with either isolated lower anatomic anomalies, or both upper and lower anatomic anomalies were not statistically more likely to have a structural renal defect than those with isolated upper anatomic anomalies (p=0.22, p=0.284 respectively). Given the high prevalence of isolated VUR in our cohort, we recommend a screening VCUG or other imaging modality be obtained to evaluate for VUR if initial renal US shows evidence of obstruction or renal scarring, as well as ongoing evaluation of renal health. PMID:25196458

  10. Tissue engineering of a bioartificial renal tubule.

    PubMed

    MacKay, S M; Funke, A J; Buffington, D A; Humes, H D

    1998-01-01

    Development of a bioartificial renal tubule with a confluent monolayer of renal epithelial cells supported on a permeable synthetic surface may be the first step to further optimization of renal substitution therapy currently used with hemodialysis or hemofiltration. Madin-Darby canine kidney cells, a permanent renal epithelial cell line, were seeded into the lumen of single hollow fibers. Functional confluence of the cells was demonstrated by the recovery of intraluminally perfused 14C-inulin that averaged >98.9% in the cell lined units vs <7.4% in the control noncell hollow fibers during identical pressure and flow conditions. The baseline absolute fluid transport rate averaged 1.4+/-0.4 microl/30 min. To test the dependency of fluid flux with oncotic and osmotic pressure differences across the bioartificial tubule, albumin was added to the extracapillary space, followed by the addition of ouabain, an inhibitor of Na+K+ adenosine triphosphatase, the enzyme responsible for active transport across the renal epithelium. Addition of albumin resulted in a significant increase in volume transport to 4.5+/-1.0 microl/30 min. Addition of ouabain inhibited transport back to baseline levels of 2.1+/-0.4 microl/30 min. These results are the first demonstration that renal epithelial cells have been grown successfully as a confluent monolayer along a hollow fiber, and exhibit functional transport capabilities. The next steps in constructing a bioartificial renal tubule successfully are to develop a multi-fiber bioreactor with primary renal proximal tubule cells that maintain not only transport properties but also differentiated metabolic and endocrine functions, including glucose and ammonia production, and the conversion of vitamin D3 to a more active derivative. A renal tubule device may add critical renal functional components not currently substituted for, thereby improving the treatment regimens for patients with acute and chronic renal failure. PMID:9617948

  11. Pseudotumor presentation of renal tuberculosis mimicking renal cell carcinoma: A rare entity

    PubMed Central

    Panwar, Anubhav; Ranjan, Raju; Drall, Nityasha; Mishra, Neha

    2016-01-01

    Tuberculosis can involve any part of the body. Urogenital tuberculosis is a fairly common extra-pulmonary manifestation of tuberculosis and renal tuberculosis is the most common form of urogenital tuberculosis. Renal tuberculosis seldom presents as a mass, usually due to hydronephrosis of the involved kidney. However in extremely rare cases it may present as an inflammatory pseudotumor which may mimic renal cell carcinoma. We present a case of a 65- year- old male who was provisionally diagnosed as renal cell carcinoma based on clinical and radiological findings and managed accordingly but was finally diagnosed as renal tuberculosis based on histopathological examination of surgical specimen.

  12. MRI appearance of massive renal replacement lipomatosis in the absence of renal calculus disease

    PubMed Central

    Fitzgerald, E; Melamed, J; Taneja, S S; Rosenkrantz, A B

    2011-01-01

    Renal replacement lipomatosis is a rare benign entity in which extensive fibrofatty proliferation of the renal sinus is associated with marked renal atrophy. In this report, we present a case of massive renal replacement lipomatosis demonstrated on MRI. The presentation was atypical given an absence of associated renal calculus disease, and an initial CT scan was interpreted as suspicious for a liposarcoma. The differential diagnosis and key MRI findings that served to establish this specific diagnosis are reviewed. Histopathological correlation is also presented, as the patient underwent nephroureterectomy. PMID:21257835

  13. [Renal angiomyolipoma: diagnosis and treatment].

    PubMed

    Arima, K; Kise, H; Yamashita, A; Yanagawa, M; Tochigi, H; Kawamura, J; Horiuchi, E; Sugimura, Y

    1995-09-01

    In 10 years the diagnosis of renal angiomyolipoma (RAML) was made in 14 patients (male-to female ratio 1:3.7) at our institution; 1 case was associated with tuberous sclerosis (TS) and 1 case had regional lymph node involvement. A statistical study was done on data taken from 739 cases of RAML in the Japanese literature, including our cases. The male to female ratio was 1 to 3. Twenty eight percent of the cases were associated with TS. The ratio of bilateral cases to the unilateral one was 1 to 3. The main clinical signs were flank pain, abdominal mass, hematuria and fever elevation. Recently the ratio of nephrectomy has decreased to 30%. The percentage of detecting the fat component by ultrasonography (US), computed tomography (CT) and magnetic resonance imaging were 88.1%, 86.5% and 80.8% respectively. The percentages of visualizing hypervascularity, aneurysms, absence of arterio-venous shunt and onion peel appearance by selective renal angiography were 77.3%, 71.4%, 48.1% and 4.9% respectively. Small (less than 3 cm), asymptomatic, simple lesions with adipose component may be observed annually by CT and US until more experiences is gained with surveillance of these patients. Embolization was useful for emergency cases or pre-treatment of nephron sparing surgery, but insufficient by itself. As there still remain problems in the diagnosis of RAML, especially in the case of very small tumors, in the case with almost no adipose component and in the case associated with renal cell carcinoma, the diagnosis of RAML should be made synthetically including angiography. PMID:7484542

  14. Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620

  15. Extramedullary hematopoiesis in renal allograft

    PubMed Central

    Chen, Guilan; Ali, Reza; Shuldberg, Mark M.; Bastani, Bahar; Brink, David S.

    2013-01-01

    Extramedullary hematopoiesis (EMH), defined as the presence of hematopoietic elements outside of the medullary cavity of bone, has been reported in patients with various hematopoietic neoplasms including myelofibrosis. EMH commonly occurs in the liver and spleen (resulting in hepatosplenomegaly) and uncommonly involves the kidney. EMH involving the allograft kidney has not been reported in English literature. Herein, we report the first case of EMH in allograft kidney in a patient with myelofibrosis. The clinical and pathological findings are described. Through comparison of the medullary neoplastic infiltrate with the renal allograft infiltrate, we postulate the neoplastic nature of the infiltrate in the allograft kidney. PMID:26120442

  16. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man.

    PubMed

    Pandya, V K; Sutariya, H C

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved the upper pole of the transplant. There was no metastasis. The patient underwent radical allograft nephrectomy for the carcinoma that had extended up to the renal hilum. Histopathological examination revealed Furhman grade-1, clear cell variant, stage pT2 N0 M0. In the last visit, the patient was on maintenance hemodialysis via arterio-venous fistula and planned for cadaveric renal transplantation. Computed tomography could facilitate early diagnosis and proper management of patients with post-renal allograft renal cell carcinoma. PMID:26889374

  17. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man

    PubMed Central

    Pandya, V. K.; Sutariya, H. C.

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved the upper pole of the transplant. There was no metastasis. The patient underwent radical allograft nephrectomy for the carcinoma that had extended up to the renal hilum. Histopathological examination revealed Furhman grade-1, clear cell variant, stage pT2 N0 M0. In the last visit, the patient was on maintenance hemodialysis via arterio-venous fistula and planned for cadaveric renal transplantation. Computed tomography could facilitate early diagnosis and proper management of patients with post-renal allograft renal cell carcinoma. PMID:26889374

  18. The renal quantitative scintillation camera study for determination of renal function

    SciTech Connect

    Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.

    1983-03-01

    The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.

  19. CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer.

    PubMed

    Min, B; Park, H; Lee, S; Li, Y; Choi, J-M; Lee, J Y; Kim, J; Choi, Y D; Kwon, Y-G; Lee, H-W; Bae, S-C; Yun, C-O; Chung, K C

    2016-07-14

    The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer. PMID:26568304

  20. Acute renal failure in general surgery.

    PubMed Central

    Slapak, M

    1996-01-01

    The high mortality and morbidity can be significantly reduced by three cardinal steps: 1. Early diagnosis of intrinsic renal failure 2. Early institution of fluid restriction and dialysis 3. The identification of patients who are likely to be at high risk from acute renal failure, and the careful planning and institution of available therapeutic measures to prevent it. PMID:9155748